Annual Report 2011–2012

Hope grows with you

TODAY’S RESEARCH, TOMORROW’S MEDICINE

Thank you to the staff of KRI who helped with the report and to the children and parents who featured in it:

Angela, Bailey, Behnam, Brooke, Holly, James, Isa, Tristan and Natalia.

Content: Helen Signy, The WriteMedia Network

Graphic Design: Sandra Marta, Smarta by Design

Photography: Michael Amendolia, Paul de Sensi

Printing: Focus Press

THANK YOU

CONTENTS

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FOREWORDS 2

OUR ORGANISATION 5

KRI INFlUENCES ClINICAl CARE 6

KRI INFlUENCES INTERNATIONAl RESEARCH AND TRAINING 9

KRI INFlUENCES POlICY AND PRACTICE 12

RARE DISEASES 14

INDIGENOUS HEAlTH 17

POPUlATION AND DISEASE-BASED COHORTS 19

ClINICAl TRIAlS – MAKING A DIFFERENCE 21

FRONTIER MEDICINE 24

STUDENTS AT KRI 26

OUR RESEARCH 28

OUR FINANCES 30

THANK YOU 32

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ElIzAbETH KOffCHIEF ExECUTIvETHE SYDNEY CHIlDREN’S HOSPITAlS NETWORK

Based at The Children’s Hospital at Westmead, many of the researchers at the Kids Research Institute are in the unique position of also being practising clinicians in the Hospital. This enables the prompt translation of scientific discovery directly into treatments for sick children.

In 2010, the announcement of the Sydney Children’s Hospitals Network (SCHN) brought The Children’s Hospital at Westmead together with the Sydney Children’s Hospital in Randwick, creating the largest paediatric entity in NSW.

As well as extending our clinical services, this amalgamation opened the door to unprecedented opportunities for research collaboration.

Now in its second year, SCHN has seen a strengthening in our research capability, the quality of our research and the outputs we are achieving.

The benefits of this collaboration extend beyond the academic stimulation brought from working together. It means that we have a larger patient population, which benefits our clinical trials work. It also means that we are in a better position to attract research funding and boost the importance of paediatric research.

The last 12 months have seen a period of further integration in the research arena, both from an operational and a governance perspective. This we are confident will best position us to respond to the recommendations of the NSW Health and Medical Research Strategic Review, chaired by Peter Wills AC and the National Research Agenda.

Our partnerships and collaborations have spread even further afield. Our long and close association with the University of Sydney, enabled by strong leadership from Professor Kathryn North, has now been augmented with partnerships with the University of NSW, University of Technology Sydney and University of Notre Dame.

I would like to thank everyone at KRI for their outstanding contributions to paediatric research. We are proud of the achievements of the past year and I look forward with confidence to continued success in years to come.

Research into child health is entering an exciting new era. There is a global push for more paediatric clinical trials; genomic medicine is opening unprecedented opportunities for diagnosis and treatment; and there is increasing recognition of the need to assess the impact of our research on health services and the community. Funding bodies nationally are recognising the importance of child research as a way of staving off the costly chronic diseases of adulthood.

I am pleased to report that the Kids Research Institute has recorded a highly successful year, in which we have been recognised for the excellence of our research, forged new partnerships and made significant gains in our research that will lead to improved health outcomes for children now and in the future as adults.

OuR RESEARCH ExCEllENCEResearchers at the Kids Research Institute are now leading and/or participating in three very different National Health and Medical Research Council (NHMRC)-funded Centres of Research Excellence (CREs). These centres are focused on providing funding for multi-disciplinary and multi-site research, training for individuals and the chance to make discoveries. These highly competitive national grants provide a ringing endorsement of the strength of the research we do here. In 2012, two out of 15 CREs awarded nationally included research leaders from KRI.

last year, we joined with Children’s Cancer Institute Australia and the Children’s Medical Research Institute in winning the Cancer Institute of NSW’s Translational Cancer Research Centre for Kids (TCRCK). Now formalised into the Kids Cancer Alliance, it is embarking on a raft of new projects that aim to translate scientific discoveries into improved outcomes and services for children with cancer.

This year, we were successful in securing over $5 million for NHMRC project grants and scholarships. Four of our researchers, Nigel Clark, Alison Tong, Germaine Wong and Tom Snelling, have been awarded competitive career development fellowships, recognising the excellence of their existing body of research and enabling them to continue their work over the next three to four years.

OuR pARTNERSHIpSBased at The Children’s Hospital at Westmead, we are in a unique position as many of our researchers are also clinicians, working with some of the state’s sickest patients. As well as the basic science conducted in our state-of-the-art facilities, we are able to translate our findings directly into improved treatment for our patients.

With access to a large population of children, we have a particular focus on clinical trials. The Paediatric Trials Network Australia, of which we are a founding member, aims to improve the quantity and quality of clinical trials in children across Australia. An enabler for the trials network will be the roll-out of a national clinical trial data management system in 2013, funded by Therapeutic Innovation Australia.

pROfESSOR CHRIS COWEllDIRECTORKIDS RESEARCH INSTITUTE

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pROfESSOR CHRIS COWEllDIRECTORKIDS RESEARCH INSTITUTE

The National Centre for Immunisation Research and Surveillance (NCIRS) has received funding until 2015. With partnerships across Australia and internationally, the NCIRS conducts vaccine research and surveillance to inform policy and practice around the world.

As a member of the Westmead Research Hub, we have access to an incredible range of cutting-edge facilities based among the diverse population of Western Sydney. New and expanded research facilities across the Hub are planned, which will double the Hub’s research capacity within the next two years.

We also have important public health partnerships. The Sax Institute is the major partner that helped achieve funding for the next five years for research into urban Indigenous health, led by Professor Jonathan Craig. The George Institute and Telethon in Perth are major partners in our work with remote Indigenous communities, led by Professor Elizabeth Elliott.

OuR SuppORTERSOur work for sick children would not be possible without the help of our many supporters. A huge thank you to our donors, who this year contributed nearly $3.5 million in much-needed donations and benefited many research projects in kids’ health – an incredible effort!

I would like to particularly acknowledge The Kids’ Cancer Project, who have contributed $3.4 million over the past 7 years for the Cancer Gene Therapy Project. The study is now in a position where the first patients are being treated in a clinical trial.

I would also like to thank our dedicated research support staff. led by Karyn Joyner, they have reviewed processes around ethics and governance and introduced new efficiencies, leading to a huge improvement in the level of support offered across the entire research facility.

lOOKINg fORWARDThe establishment of SCHN means we are now operating in the largest clinical service for children in this country. It opens enormous opportunities for clinical trials, translational research, public health outcomes and health effectiveness research.

Our research not only benefits the sick children of today, but the whole community tomorrow. With continued support and advocacy, we look forward to a bright future as we transform our work into better health for kids.

OUR vISIONTo be a leading global centre for clinical translational research in children.

OUR MISSION To improve children’s health outcomes and drive excellence in health by:– Discovering new insights into how diseases work, diagnostic methods and treatments – Translating research outcomes into clinical practice within the Hospital and community – Finding which potential treatments are effective and safe via the Clinical Trials Centre – Working collaboratively locally, nationally and internationally to improve children’s health.

ABOUT THE KIDS RESEARCH INSTITUTEWe are the research arm of The Children’s Hospital at Westmead, located near Parramatta in Sydney’s West. We are a key member of the Westmead Research Hub, the largest medical research precinct in NSW, and one of the research entities of the Sydney Children’s Hospitals Network.

Our 270 research and support staff are committed to discovering new ways to improve the health of children. Many of our researchers are also clinicians, ensuring our world-leading research is quickly translated into treatments for their young patients.

Our work comprises three main areas: basic science in the laboratory to understand disease processes in children; clinical research to develop better diagnostic techniques and treatment methods; and population health research to understand the impact of disease in the broader community.

We encourage collaboration, both with our key partners the University of Sydney, the Children’s Medical Research Institute and Westmead Millennium Institute, and with many other prestigious institutions in Australia and overseas.

OuR ORgANISATION

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guIDINg bETTER CARE fOR DIAbETES pATIENTSSince the NHMRC’s last diabetes guidelines were published in 2005, much has changed in diabetes care.

New technology means about half of patients have diabetes pumps to deliver their insulin automatically; telehealth has enhanced communication between healthcare providers and patients; and there is more evidence of the importance of controlling blood sugar levels in children.

Associate Professor Maria Craig and her team at the Institute of Endocrinology and Diabetes were asked by the Department of Health and Ageing to revise the earlier paediatric guidelines and produce new guidelines along the entire lifespan.

The work involved conducting systematic reviews of the medical literature, consulting with experts in endocrinology, nutrition, education and psychology, and pooling the information into one user-friendly document.

The new guidelines were approved by the NHMRC and launched on World Diabetes Day on November 14, 2011.

Since then, the team has been involved in disseminating the guidelines to GPs and other practitioners.

“This is a more holistic document, recognising the risk of depression and anxiety, and that avoiding injections in young children is not a good idea because failing to achieve good control now will lead to problems later on,” said Associate Professor Craig.

lOOKINg AT WHAT’S REAllY gOINg ON IN THE bRAINS Of CHIlDREN WITH ADHDWhen we look at images of the brain, it becomes apparent that some children who are diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) have issues in other parts of their brain, such as mood disturbance – meaning different medications may be more suitable to treat them.

KRI is looking at the brain and hormonal causes of ADHD and has developed technology to identify biological markers of the condition.

It has developed a tool which is being used worldwide to diagnose children suspected of having ADHD. The effectiveness of this diagnostic tool is now being assessed in sites across Australia.

“We have found that with kids labelled with ADHD, other things can at least contribute to their clinical presentation, if not explain it,” said Dr Michael Kohn, co-director of the Department of Adolescent Medicine and Eating Disorders.

“For example, if they have anxiety they are too easily aroused, which can lead to increased distractibility. Knowing this means they can be treated with non-stimulant medication.”

NADIA bADAWI: A NEW STRATEGY TO PREvENT CEREBRAl PAlSY less than 10% of cerebral palsy is caused by a lack of oxygen to the brain during birth; in many other cases, we simply don’t know the cause.

professor Nadia badawi, the Director of the grace Centre for Newborn Care, is working with the Cerebral palsy Alliance Research Institute based at the university of Notre Dame to identify the best world research into prevention and cure for cerebral palsy.

One of the most exciting breakthroughs is that giving an intravenous injection of magnesium sulphate to women before they go into preterm labour can reduce the rate of cerebral palsy in premature babies by about 30%.

“Cerebral palsy is the most common physical disability of childhood, and it’s a lifelong condition. We are trying to cut short the huge lag between research and clinical practice by implementing injections of magnesium sulphate as widely as possible,” she said.

That means publicising the findings as widely as possible and trying to convince obstetricians across Australia of the value of the intervention.

Since professor badawi started at the grace Centre 15 years ago, the mortality rate for babies has dropped from nearly 20% to less than 3%.

“As we talk less about survival, because it’s more of a given, looking at the quality of life has become more important to all of us,” she said.

KRI INfluENCES ClINICAl CAREAll of the researchers at KRI are working towards a common goal: to improve child health. Our research spans the laboratory bench to the bedside, and many of our findings are translated into improvements to the way clinicians practice.

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EACH YEAR, THE CHIlDREN’S HOSpITAl AT WESTMEAD pERfORMS bETWEEN ONE THIRD AND ONE HAlf Of All pAEDIATRIC KIDNEY TRANSplANTS IN AuSTRAlIA. A MAjOR fOCuS Of KRI’S RESEARCH IS TO fIND WAYS TO MAKE TRANSplANTATION bETTER.

A kidney transplant saved six year old bailey’s life – but, like any transplant patient, he has to take medication every day to stop his body rejecting the new kidney. These immunosuppressive drugs mean he’s vulnerable to any infection that’s going around.

“I’m always worried about him when he’s around other children who are sick. He picks up things really quickly,” said his mother, Melissa.

“We also know that his new kidney won’t last forever.”

The team at the Centre for Kidney Research (CKR) is working on ways to prolong the life of transplanted organs and to prevent rejection in transplant recipients like bailey.

“Our strategies either enhance the body’s own way of protecting against injury, or remove parts of the immune system which cause rejection and damage,” said the Centre’s Head of laboratory Research, Associate professor Stephen Alexander.

One trial has looked at the possibility of transplanting some of the donor’s own immune system along with the new organ, which could one day give patients a natural tolerance without the need for immunosuppressive drugs. Another area of research involves giving the patient a DNA injection to prevent the original kidney damage.

CKR is also involved in the large international goCAR study looking at the genetic profile and immune response of people who have had kidney transplants to try to understand why rejection sometimes occurs.

Children like bailey have an increasingly bright future. He was born with congenital nephrotic syndrome, a genetic disorder which meant he developed protein in his urine and made his body swell. Regular hospital visits and a raft of medication and supplements initially controlled his condition, but when he turned three his kidneys failed altogether. Dr bruce bennetts at The Children’s Hospital at Westmead has set up national testing for genes that cause this problem.

bailey spent three months on dialysis until he was transplanted with a kidney from his father, Anthony. The operation went very well and now bailey is able to go to school, play and dance hip hop with his friends.

A BETTER FUTURE FOR TRANSPlANT PATIENTS

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HOME vISITS STAvE Off ObESITY IN TODDlERSSetting up healthy habits in early childhood can last a lifetime. KRI researcher, Professor louise Baur, and colleagues at the University of Sydney and South West Sydney local Health District have shown that intervening to improve children’s eating and exercise habits before they turn two can reduce childhood obesity – and hopefully set children on a healthy trajectory.

The ‘Healthy Beginnings’ randomised controlled trial, published this year, showed a significantly lower Body Mass Index (BMI) in children whose mothers were paid regular visits by community nurses to talk about nutrition, exercise and screen time.

The first time mothers who received eight visits over two years also gave their children more vegetables, breastfed for longer, and engaged in more physical activity themselves.

“Being large at birth and then experiencing rapid weight gain in the first few months puts children at risk of excess weight gain later in childhood and early adulthood,” said Professor Baur, head of the Obesity Research Group.

“Unlearning unhealthy behaviours is hard and they tend to track for life. They become a risk factor for other things.”

The Obesity Research Group is also launching a community-based treatment program for children aged five to nine, which tackles their obesity through a parenting program. Already proven to be effective in studies in NSW, this Parenting, Eating & Activity for Child Health (PEACH) program is now being rolled out in South Australia and Queensland.

HEARTbEADS gO INTERNATIONAlEvery time sick children in the cardiac ward have a painful or stressful procedure, they are given a coloured bead. The string of beads that results over the course of their treatment becomes a powerful reminder for children and their families of their personal journey in hospital.

This Heartbeads program has been embraced by Heart Kids Australia, which has made it available to children across the country. Now hospitals in the UK and Denmark are launching their own heartbeads projects.

“These beads are narratives of the heart. They let both families and children tell a story of the range of their experience, which is unique to them,” said Professor val Wilson, Head of the Nursing Research & Practice Development Unit, which initiated Heartbeads some years ago.

The Unit is now embarking on a study of 950 families who have been involved in Heartbeads to determine what they mean for families.

“We didn’t anticipate in the beginning how important the beads would be for parents. But they want them, there’s no doubt about it. They are an acknowledgement of the child’s life and how hard everyone fought for that life.”

KRI INfluENCES ClINICAl CARE

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OuR CENTRES Of RESEARCH ExCEllENCEThe Centres of Research Excellence (CRE) scheme provides government funding through the NHMRC to support teams of researchers to work collaboratively.

KRI won two of 15 of these highly competitive grants awarded this year, along with one awarded last year. The funding is enabling some of our most recognised professors and post doctoral research fellows to participate in internationally recognised research in their chosen area.

The advantage of research as part of a CRE is that it enables people to work with other disciplines and across multiple sites. As well as creating new science, the CREs foster collaboration and training of researchers to build our capacity for the future.

One of the new CREs, led by Professor Kathryn North, focuses on finding targeted therapies to treat weakness in children who have neuromuscular disorders. With many more children being accurately diagnosed than 10 years ago, the current emphasis is to translate laboratory research into best clinical practice for thousands of patients.

The second CRE, led by Professor Peter McIntyre, involves improving immunisation of people who are vulnerable to severe disease or because they may miss out on vaccinations, such as the very old or young, pregnant women, Indigenous children, migrants and refugees.

The third CRE, led by Professors Cheryl Jones and Robert Booy, commenced in 2011 has been running for a year now. It aims to identify ways to prevent and reduce the burden of disease from critical infections. It has set up national surveillance for encephalitis and investigates newly emerging infections or infections passed from mother to child.

ElITE ATHlETES SHED lIgHT ON MuSClE DISORDERSDNA from elite athletes – including many Olympians – is being used at KRI to study the way muscle works at an elite level.

Researchers Kate Quinlan and Peter Houweling are studying the role of alpha-actinin-3, a protein which influences the way muscle functions. People who have alpha-actinin-3 are able to run fast, while people who don’t are able to run long distances.

DNA from around the world has been collected from elite sprinters and endurance athletes, so that researchers in an international collaboration can better understand the role our genetics plays in muscle performance and why the absence of alpha-actinin-3 increases endurance.

This not only enhances our knowledge of muscle performance, but may provide information that will lead to novel treatments of muscle disease and weakness.

“Alpha-actinin-3 was discovered in our lab and is the best characterised gene for athletic performance in the world,” said Drs Quinlan and Houweling.

“We know mice without alpha-actinin-3 can run further before they get exhausted. Now we’re seeing they also respond better to endurance training. That might shed light on problems like muscle atrophy and other complications of ageing and muscle disease, providing additional information that we can apply more widely in the future.”

KRISTY ROSE: TREATING CHIlDREN WITH NEUROMUSCUlAR DISEASElargely due to the work of the Institute for Neuroscience and Muscle Research (INMR), today it is possible to diagnose more than 60% of causes of neuromuscular disease – compared to 10% a decade ago.

physiotherapist Dr Kristy Rose is being funded by an NHMRC Centre of Research Excellence grant to conduct postdoctoral research into better ways of treating these children after diagnosis.

One exciting new area is using whole body vibration training to enable children with nemaline myopathy to exercise. This congenital condition causes muscle weakness which means many patients are confined to a wheelchair.

When children stand on a vibration plate, the muscles in their legs and torso are forced to contract. This not only conditions the muscles but also pulls on the bones, which is thought to boost bone mineral density.

Dr Rose’s varied research covers a range of other neuromuscular conditions. Her current projects include ankle instability in children with a particular type of Charcot-Marie-Tooth disease; reducing side effects of steroids in boys with Duchenne muscular dystrophy by trialling a new drug; and investigating muscle weakness in children with the genetic disorder Neurofibromatosis type I.

“I have worked in this area for 10 years and these kids are like family to me,” said Dr Rose.

“It is exciting to be able to research better clinical interventions for these children. Most of them are involved in our research studies, which also means they receive more frequent monitoring and so have better outcomes.”

KRI INfluENCES INTERNATIONAl RESEARCH AND TRAININgOur collaborations extend throughout NSW, Australia and internationally. Our high quality work adds to the body of global knowledge about child health and influences research and training around the world.

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THE CAuSE Of ENCEpHAlITIS, OR SWEllINg Of THE bRAIN, IS STIll uNKNOWN IN MORE THAN HAlf Of CASES. IT CAN KIll IN HOuRS AND lEAvES MANY OTHERS WITH bRAIN DAMAgE AND OTHER MAjOR COMplICATIONS.

five year-old behnam went from a sniffle and a headache at a birthday party on Saturday to intensive care by Monday morning.

“It’s an awful thing to see your child deteriorate and think you are going to lose him,” said his mother, fiona.

behnam was transferred to The Children’s Hospital at Westmead from his local hospital. fiona and behnam’s father, Matthew, said goodbye to him as he was being wheeled off to have an MRI. The next time they saw him he was in a coma, paralysed and unable to breathe alone.

Tests later revealed he had contracted the H1N1 virus, or swine flu, which led to acute disseminated encephalomyelitis that had affected his spinal cord, causing paralysis. Doctors diagnosed an autoimmune cause of his condition and immediately administered steroids and intravenous immunoglobulin.

“It was amazing how quickly it worked,” said fiona. Within a week behnam was out of ICu. He gradually recovered over the next few months and today, at 8, the only reminder of his ordeal is a weakness in his left foot.

In a bid to identify new causes of encephalitis, professors Cheryl jones and Robert booy from KRI are establishing encephalitis surveillance through ICus and paediatricians across Australia. They plan to collect samples from all children who contract the illness then use sophisticated high throughput genetic sequencing to search them for every known virus and bacterium in humans.

They are also researching how encephalitis can be caused by an autoimmune response, or by viruses like herpes or influenza.

“This international collaboration will enable us to do the best possible pathogen discovery in the world, looking to understand the causes of encephalitis which will lead to better treatment and outcomes and also better diagnostic tests,” said professor jones, of the Centre for perinatal Infection Research.

“These are uncommon conditions and difficult populations to study. We are uniquely located in a position where we can influence policy and practice.”

FROM FlU TO ICU: WORK TO TARGETlIFE-THREATENING ENCEPHAlITIS

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OuR DISEASE MEASuRINg TOOl INTRODuCED WORlDWIDEFor clinical trials to provide accurate information, it is important that appropriate patients are chosen to participate and their outcomes measured properly.

There are more trials being run to treat Charcot-Marie-Tooth disease (CMT), the most common inherited neurological disorder, but until now it has been impossible to measure accurately the severity of the disease and the patient’s response to treatment in children.

Associate Professor Joshua Burns from the Institute of Neunoscience and Muscle Research, along with colleagues from the United States, the UK and Italy, has designed the world’s first rating scale for children with CMT.

The CMT Pediatric Scale (CMTPedS) has been evaluated and shown to be a reliable and invaluable tool for measuring children’s disease – leading to more accurate clinical trials, better treatments and improved outcomes.

The Scale, published in the May 2012 edition of Annals of Neurology, has been introduced around the world, including being listed by the National Institutes of Health in the United States as the best outcome measure for children with CMT.

KRI INfluENCES INTERNATIONAl RESEARCH AND TRAININg

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A TWO-YEAR pROjECT TO REWRITE AuSTRAlIA’S IMMuNISATION ‘bIblE’ The Australian Immunisation Handbook is published by the Government to provide clinical guidelines for everyone in Australia who delivers vaccinations. It covers everything from the latest research on immunisation, practical information on giving vaccines, and how to follow up any adverse events.

The National Centre for Immunisation Research and Surveillance (NCIRS) has provided a team of technical editors and writers to produce the next Handbook, which is due for publication in 2013.

For two years they have been identifying the relevant evidence, conducting literature reviews and writing policy as well as working with peak advisory committees around Australia to formulate new recommendations.

The new Handbook, which will be in its tenth edition, contains updated information about special vaccination requirements, HPv, influenza, whooping cough and pneumococcal vaccines, and provides a more comprehensive overview of the benefits and risks of immunisation.

From next year it will be used by doctors and nurses in clinics, schools and other settings across the country to ensure vaccines are delivered in the safest and most effective way possible.

RESEARCH TO bOOST Hpv vACCINATION IN SCHOOlSSince the HPv vaccine was introduced in 2007, the world has been watching Australia closely due to the success of our school-based vaccination program.

Australia is vaccinating more than 70% of school age girls with the three doses of the HPv vaccine, with over 80% receiving at least one dose – much higher than is being achieved in the United States and Europe. In contrast to Australia, these countries require adolescents to visit their family doctor to be vaccinated. Early data in Australia is already showing a marked reduction in HPv infection rates, genital warts and pap test abnormalities in young women who were offered the vaccination at school.

With the announcement that boys will also receive the HPv vaccination from next year, KRI is researching ways to further improve school-based vaccination programs and ensure their success into the future as additional vaccines are recommended for adolescents.

It has found girls, their parents and teachers do not fully understand the HPv vaccine, and has developed a range of initiatives and resources to support informed consent and vaccination day processes. The aim is to promote higher consent and vaccination completion, while improving understanding among all involved and reducing fear of the pain of the injection in adolescents.

These school HPv vaccination program initiatives are being evaluated in schools in Western Australia and South Australia, and if effective may be introduced nationally.

“We believe this approach will support and improve the process of getting adolescents vaccinated through schools,” said Associate Professor Rachel Skinner, who is conducting the study.

“We are already seeing some really important health outcomes from the national HPv vaccination program, and it is critical schools continue to support vaccination programs into the future.”

DANNY CASS: lITTlE CHANGES THAT CAN MAKE A HUGE DIFFERENCE TO KIDS’ SAFETYAs a trauma specialist at The Children’s Hospital at Westmead, professor Danny Cass sees at least one child a day who has received serious injuries requiring a complex team approach for treatment.

from talking to the children’s families, he and his team have been able to gather a rich history of the sequence of events leading up to the accident. They realised that often quite simple approaches could have prevented these terrible injuries, such as fencing inflatable pools or erecting a barrier to stop children falling out of high windows.

The high number of children with fall injuries led him to set up the Kids Don’t fly campaign. A taskforce produced a detailed document on necessary interventions, which was quickly adopted by Canberra and has led to changes to the national building code. As a result of professor Cass and the teams’ initiative, from 2013 Australia will become the only country in the world to mandate child safe windows in all new buildings.

Now professor Cass and the team have turned their attention to preventable drowning in inflatable pools, which constitutes nearly half of all the drowning cases presented to the Hospital each year. Suggestions include selling a cheap and easy to erect fence along with the pool, and educating parents about the need to drain water after use.

“We have found that the community listens to data that comes from a Children’s Hospital and are often very willing to make changes,” he said.

“Most of the injuries we see could have been prevented. That’s what motivates us.”

KRI INfluENCES pOlICY AND pRACTICEImproving child health is as much about changing the way people do things as identifying new treatments. KRI is researching what works best, and its findings are influencing policy and practice worldwide.

THE DIffICulT TRANSITION fROM CHIlDHOOD TO ADulTHOOD IS HARD ENOugH fOR ANYbODY, buT fOR YOuNg pEOplE WITH CHRONIC IllNESSES AND COMplEx MEDICAl NEEDS IT CAN bE EvEN HARDER. KRI IS ADDRESSINg THEIR pROblEMS bY uSINg TECHNOlOgY TO HElp THEM lEARN TO SElf-MANAgE THEIR CONDITIONS.

At 16, not only did brooke have to juggle the demands of Year 11, a part time job and her social life, but she had to remember to take handfuls of pills every day and attend numerous medical appointments.

When she was 13, brooke received a double lung transplant because her lungs were failing due to cystic fibrosis. for nearly the whole of Year 8 she was confined to a bed and on oxygen, unable to move without a wheelchair and the help of her family.

The transplant gave her back her life but managing the complicated medical regime of a transplant recipient is sometimes hard.

“Mum will tell me I have an appointment but then the day will come and I’ll go to TAfE and I’ll completely forget,” she said.

KRI is researching the issues facing teenagers as they start to manage their conditions themselves, rather than relying on their parents as they have done their whole lives. It plans to establish a Self-Management Clinic next year.

Dr Damien McKay plans to assess adolescents’ individual needs with the help of technology they can all relate to – an ipad.

Dr McKay, a Marie bashir Medical Research fellow with the Academic Department of Adolescent Medicine, working together with professor Kate Steinbeck, foundation Chair of Adolescent Medicine at the university of Sydney, will be using newly developed assessment questionnaires in the format of an app, which enable teenagers to answer quite personal questions so that any barriers to self-management can be identified.

“Teenagers find it confronting to be asked these sorts of questions by someone,” said Dr McKay.

“The beauty of the ipad is they can perform that assessment in what’s very familiar technology for them and in a non-confronting way. We are trying to tap into that and use it in a clinical and a research setting.”

Eventually it is hoped similar technology might be used to remind people to take their medications and to motivate them to manage conditions ranging from chronic illnesses like diabetes to obesity and insulin resistance.

brooke passed away in late 2012 and it is her family’s hope that her contribution to the use of this technology will support other children in the future.

SPEAKING TEENAGERS’ lANGUAGE – WITH THE USE OF TECHNOlOGY

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TOWARD A bREAKTHROugH fOR CHIlDREN WITH pKuPhenylketonuria (PKU) is a genetic condition in which children are born without an enzyme that breaks down an amino acid called phenylalanine in protein. Phenylalanine can build up in the bloodstream and become toxic, potentially leading to severe mental retardation and seizures.

Currently the only therapy is a very restricted diet, cutting out most protein and dairy products – even chocolate and ice cream.

But researchers at the Western Sydney Genetics Program have developed a genetically modified probiotic, using an enzyme present in parsley, which will break down phenylalanine. It’s hoped that one day children who take the GM probiotic will be able to eat a more normal diet.

Donations from the PKU Association of NSW Inc and Australian Rotary Health have enabled the probiotic to be tested in mice. The success of this work has led to grant funding and the ability to negotiate with other funding bodies, bringing relief for PKU patients a step nearer to reality.

gENETIC SEquENCINg OpENS DOOR TO DISCOvERYIt took 13 years and several billion dollars to sequence the first human genome. less than a decade later, technology has advanced to the point that entire genomes can be sequenced in a matter of weeks and at a cost that makes diagnostic and research possibilities available to hospitals around the world.

That means that rather than running endless tests on sick children who clearly have a genetic illness, doctors can sequence their entire genome to pinpoint the problem exactly.

‘Exome’ sequencing is a laboratory process in which the DNA that contains the code for all of the proteins in the human body is analysed in one experiment. Most of the DNA faults that lead to disease are located in this part of our DNA. KRI is collaborating with genetic research units around the world to use this technique to search for new genes responsible for disease.

Together with the Broad Institute in Boston, the Institute for Neuroscience and Muscle Research (INMR) is fine-tuning the use of exome sequencing to identify new genes responsible for muscle and nerve diseases. Already three new disease genes have been identified this way this year.

“Finding the genes that cause genetic disease is essential, it’s the first step in thinking how we can treat these conditions,” said Dr Nigel Clarke.

The INMR has installed a next generation sequencer in the lab which has improved its ability to check the sequence of large genes on site. It will be the first centre in Australia to use this technology to look at the very large RYR1 gene, a common cause of muscle disease.

Genetic sequencing is also offering answers in heart research. Every family which brings a child to The Children’s Hospital at Westmead for cardiac surgery is asked to contribute their child’s DNA for research. Three and a half thousand specimens have been collected, building a valuable resource and one of few of its kind in the world.

Exome sequencing is being applied to find the genetic basis of hypoplastic left heart syndrome, a congenital disease which leaves children with only one functioning heart ventricle and a severely restricted lifestyle.

This approach is also being used to investigate the genetic causes of more common forms of congenital heart disease. The information is being combined with insights from the first genome-wide association study in congenital heart disease, an international collaboration of which Kids Heart Research is part of.

“The central aim is to be able to provide individualised information for families who have a baby affected by congenital heart disease, apparently out of the blue,” said Associate Professor David Winlaw, head of Kids Heart Research.

RARE DISEASESAbout half a million families live with a child who has a rare disease. As well as the complexities of their condition, they are challenged by a lack of medical knowledge and support. With many of these children referred to our Hospital, research into rare diseases is a major focus of our work at KRI.

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lITTlE ISA IS ONE Of ONlY TWO CHIlDREN IN THE WORlD WITH MITOCHONDRIAl RESpIRATORY CHAIN DISORDER COMplEx III. uSINg SOpHISTICATED gENE SEquENCINg TECHNIquES, RESEARCHERS AT KRI HAvE IDENTIfIED A pREvIOuSlY uNKNOWN gENE WHICH CAuSES HIS DISORDER.

Isa was just five months old when he first got sick. He developed a fever and within minutes was dangerously ill.

Transferred from his local hospital to The Children’s Hospital at Westmead, Isa spent 10 days in ICu. Doctors thought he had a metabolic disorder, but they could not diagnose it accurately.

When he relapsed a few months later, a biopsy was taken from his liver and the samples were sent to laboratories in Melbourne and Canada for genetic sequencing.

New technologies have sped up the process of gene discovery. New techniques mean children’s entire genome can be sequenced in a matter of weeks, and at a fraction of the cost that the process took a decade ago.

That’s leading to the discovery of genes responsible for several rare diseases. While the conditions may not be curable, it means families can receive genetic counselling or have Ivf to prevent the condition when they have another baby.

Six months after his tests were sent off, Isa’s condition was diagnosed. The extremely rare mitochondrial respiratory chain disorder complex III causes him to have recurrent episodes of acidosis, meaning there is too much acid in his blood. While there is no treatment for this condition, it is being managed with vitamins.

genetic testing of the whole family showed that Isa inherited one receptive gene from his father and one from his mother. His two older siblings do not have the condition and his new brother will soon be tested too.

“What it means is we now will have the capacity to identify this in other children with a similar clinical picture,” said Director of the Western Sydney genetics Research program, professor john Christodoulou.

“We are now in a position to offer much more accurate genetic information to the family and hopefully prevent recurrence.”

FINDING THE ANSWER INISA’S GENES

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If HOllY HAD CEREbRAl pAlSY OR DOWN SYNDROME SHE WOulD HAvE bETTER ACCESS TO SuppORT – buT bECAuSE HER DISEASE IS SO RARE, THERE ARE fEW SERvICES TO HElp HER.

When Holly was diagnosed with congenital disorder of glycosylation type 1a, a rare metabolic condition that causes severe global developmental delays, her parents were told they would probably never hear her talk.

but when she said her name for the first time, at six, it was one of the best days of their lives.

“We thought we would never hear her say her name or say ‘I love you’ or dance in a tutu like other little girls – and she’s achieved all those things and more,” said her mother, Rachel.

After years searching for a diagnosis, Rachel gave up her career as a business analyst to care for Holly. She needs ongoing support from a raft of specialists such as physiotherapists, occupational and speech therapists.

finding the right support for her has paid off. When one therapist showed her how to communicate with an ipad, Holly began to speak for the first time.

“We have found ways and means of getting Holly the things she needs, but it’s been a huge struggle and it’s come at huge financial cost. It’s not as straight forward as having a child with a more common condition,” said Rachel.

Research shows a heavy psychological, financial and social impact on families who have a child with a rare disease. parents feel unsupported, they have difficulty finding health professionals who are able to help them, and they receive little support for the emotional burden.

The Australian paediatric Surveillance unit (ApSu) is heavily involved in advocating for children with rare diseases and has received an Australian Research Council (ARC) grant to study their impact on families. It also works in partnership with advocacy groups like the Smile foundation and Steve Waugh foundation, which play an invaluable role in supporting families.

The ApSu which has facilitated research into rare diseases for 20 years, is a founding member of the National Rare Disease Committee, which aims to progress a national and international plan to gain support for children with rare diseases.

A vOICE FOR CHIlDREN WITH RARE DISEASES

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STuDY OpENS WINDOW Of OppORTuNITY TO IMpROvE AbORIgINAl HEAlTHIt is often said that little can be done to improve Indigenous health because Aboriginal children are born at risk of poor outcomes.

However a major study of kidney disease in Aboriginal children, run by the Centre for Kidney Research (CKR), has turned that theory on its head.

The ARDAC study of 2000 children across NSW, the largest ever long-term study of early markers of kidney and cardiovascular disease in Indigenous children in Australia, found Aboriginal children showed no more risk factors for these diseases than non-Aboriginal children.

However those risk factors did appear when the children turned 15 or 16.

“That’s fundamentally good news because often it’s been said that with Aboriginal children, the die is cast even before birth,” said Professor Jonathan Craig, CKR’s Head of Clinical Research.

“We are showing there is a window of opportunity in late adolescence to early adult life to turn around the trajectory of ill health.”

It’s at this critical phase of young adult life that disadvantage, reflected in poor medical care, diet and lifestyle problems, begins to present with increased Body Mass Index (BMI) and blood pressure, diabetes and kidney disease.

Based on the findings of the ARDAC study, it will be possible to target intervention programs at young adults rather than school aged children, ensuring they have a healthy future.

HASANTHA guNASEKERA: WHY DO SO MANY ABORIGINAl CHIlDREN IN OUR CITIES HAvE EAR PROBlEMS?The SEARCH study (Study of Environment on Aboriginal Resilience and Child Health) is one of the first in the world to examine health outcomes in Indigenous children living in cities. Almost all previous Indigenous health studies have been done in rural areas.

The study has shown that a quarter of the 1700 urban Aboriginal children screened had ear disease and many had hearing problems and difficulties with speech and language which could affect their ability to learn at school.

Severe ear disease affected 1 to 2 per cent of the children tested – much lower than in Indigenous groups in rural Australia and overseas, but still significantly higher than non-Aboriginal children.

“Even from an early stage, just through simple things like not being able to hear well because of middle ear problems, the trajectory of disadvantage, poor education and poor health outcomes begins,” said Dr Hasantha gunasekera, one of the chief investigators of SEARCH.

As part of the study, a team of audiologists and speech pathologists assess the children when they come to their local Aboriginal Medical Service. families are alerted to any problems and children with severe disease are referred to specialists.

The data collected over the years will be combined with data on other health issues affecting the children, such as housing, mental health and nutrition.

INDIgENOuS HEAlTHThe health of Indigenous children is of critical concern in Australia. KRI researchers are involved with important projects both in cities and in remote areas to address some of the most pressing issues.

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fOETAl AlCOHOl SpECTRuM DISORDERS (fASD) ARE IMpORTANT buT OfTEN uNRECOgNISED CONDITIONS OCCuRRINg ACROSS AuSTRAlIA. fASD MAY RESulT WHEN MOTHERS DRINK AlCOHOl WHIlE THEY ARE pREgNANT. AlCOHOl CAuSES bRAIN IMpAIRMENT, lANguAgE, lEARNINg AND bEHAvIOuRAl pROblEMS.

professor Elizabeth Elliott from KRI and the university of Sydney has been working with the george Institute for global Health, Nindilingarri Cultural Health Services and Marninwarntikura Women’s Resource Centre in fitzroy Crossing to study the prevalence of fASD in remote Indigenous communities in the Kimberley. She has also been involved in developing a screening and diagnostic tool for fASD and is working on a national plan to address the condition.

for grandmother Marmingee Hand from remote fitzroy Crossing in Western Australia, it’s a full time job to look after her two nephews and two grandchildren who live with her – especially as all have been diagnosed with fASD.

“It’s a challenge every day, but my husband and I accommodate their needs, every day it’s different,” she said.

“It’s hard work but these children have a right to be cared for, to go to school and to feel safe. It’s a brain based disability so you have to understand them and work with them.”

“One of the key aspects of our project has been education in the community to raise awareness about fASD,” said professor Elliott, a chief investigator of the lililwan project which is being run to address fASD in the fitzroy valley.

The team has developed a standardised management plan for all the children it has identified as having fASD using a multidisciplinary assessment model and has arranged health and educational support for children, such as educational support or management of behavioural, hyperactivity or attention problems.

This year the team was invited to speak to the uN’s permanent forum on Indigenous Issues in New York, where it presented the lililwan project and a film called ‘Tristan’, about one of Marmingee’s foster children.

“The film was recently presented to a bush meeting for women held at Mimbi near fitzroy Crossing and since then people have begun to fully understand the implications of fASD for children,” said Marmingee.

“It’s really hard to get diagnosed. The film made people realise it does exist and made them aware about these children’s difficulties.

“If the Marulu team or the lillilwan project didn’t happen, we would not have had the support from people like professor Elliott and professor jane latimer to make people aware of our issue with fASD.”

PROvIDING CARE AND DIAGNOSIS FOR CHIlDREN WITH FASD

Tristan on the Banks of the Fitzroy River – Photo by Elizabeth Elliott

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jOININg THE DOTS ON HEAlTH DATAThere is a lot of data about people held in government departments throughout Australia, but its use in research has been limited.

A rapidly expanding research area in Australia involves linking this data to develop a large cohort which can be studied to gain valuable health information that has never been available in this way before.

Dr Robert Menzies, Deputy Director of the National Centre for Immunisation Research and Surveillance (NCIRS), is involved in a project to link data from the Australian Childhood Immunisation Register, the NSW and federal health departments and other government sources to gain a clearer picture of the effect of vaccines in the community.

No individuals are identified, but it is possible to measure the effects of a vaccine on specific people. For example, previously researchers could look at the number of hospitalisations, but there was no information on whether one patient was returning to hospital several times for the same condition, or whether or not they were vaccinated.

The study, funded by an NHMRC Centre for Research Excellence grant, has the potential for the first time to show how effective vaccines are in certain sub groups in reducing hospitalisations and deaths, and in reducing the burden of disease in the community.

“Before you had to do an expensive study just to look at one vaccine. But this data set enables us to do lots of studies on different vaccines,” said Dr Menzies.

“Data linkage can make science much more efficient.”

pROvIDINg THE EvIDENCE bEHIND TREATMENTSThe Cochrane Collaboration is an international network of more than 28,000 people in 100 countries who work to review all the scientific studies that are published and produce the best available evidence to guide the treatment of patients.

The Cochrane’s renal group is based at The Children’s Hospital at Westmead and is responsible for reviewing world evidence around kidney disease and transplantation.

Its work involves finding all the relevant studies – not just those that are published many times – and then reviewing them systematically.

“We don’t just find the studies, we conduct critical appraisal of them and we synthesise the evidence to get a summary estimate of the effects of a particular intervention across all the studies,” said Professor Jonathan Craig, Co-ordinating Editor of the group and Clinical Head of the Centre for Kidney Research.

“This work is informing the way kidney disease is being treated all over the world.”

This year the group has made two important findings: a drug widely used for treating organ rejection was withdrawn from the international market following a Cochrane review, and more evidence has been provided about the benefits of giving drugs called Il-2 receptor blockers to improve graft survival.

AN EMERgINg pROblEM: RICKETSEven in a sunny country like Australia, children are still coming to The Children’s Hospital at Westmead with rickets (a softening of the bones) caused by a deficiency of vitamin D.

paediatric endocrinologist Associate professor Craig Munns of the Institute of Endocrinology and Diabetes published a paper in 2012 showing a high incidence of Australian children with vitamin D deficiency rickets. He identified that most of the nearly 400 children under 15 years of age had dark skin or came from refugee communities.

He is now working to find the best way to treat these children and reverse their symptoms.

“Currently the children have to take medicine every day for 80 days. We are hoping to reduce that to once a week for four weeks,” he said.

The trial involves giving one group of children with vitamin D deficiency the normal treatment, and the other group a very high dose once a week.

Associate professor Munns’ other work to improve bone health includes studying children with primary bone disorders like osteogenesis imperfecta and disorders associated with secondary osteoporosis like Duchenne Muscular Dystrophy and spinal cord injury. He is also involved in a NHMRC-funded trial of medical treatment for perthes disease.

pOpulATION AND DISEASE-bASED COHORTSKRI is heavily involved in research into large populations, or cohorts. Analysing data from these large community-based research programs gives us the information we need to identify and manage important health issues.

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TWINS ETHAN AND jAMES WERE bORN WITHIN MINuTES Of EACH OTHER, buT THE DIffERENCES IN THEIR DEvElOpMENT ARE AlREADY ClEAR fOR ANYONE TO SEE.

Ethan is growing quickly and developing as normal, while james had a major setback because he needed an operation two days after birth to fix an obstruction of his large intestine.

james has made great progress during his recovery in intensive care at the grace Centre for Newborn Care. but research at KRI has shown that newborn babies who have surgery need more specialised care as they grow up than was previously thought.

The international DAISY study is looking at the long term outcomes in babies who have surgery early in life. It was already known that heart surgery could lead to developmental delays as babies grew, but the study has shown that any surgery can have a negative effect.

At both one and three years, even babies who had relatively minor surgery and who had no other risk factors were behind other children in language, cognition and motor development.

It is still unclear what causes the developmental delay, but there are probably many factors: the babies are born with congenital problems, they receive a large amount of anaesthetic and other medications when they are very small, and possibly the brain goes through a crucial stage of development in the days after birth.

However now the problem has been recognised, clinicians can take steps to ensure that these babies receive the services they need to boost their development as they grow up.

The Children’s Hospital at Westmead has already established a follow up clinic for children who had surgery as newborns.

“Our babies are doing really well – and better than any other country, probably because most of this work is done in just one or two specialised centres in Australia and we have a good health system,” said head of the grace Centre, professor Nadia badawi.

“but this study has made us and others realise we need to think what we can do to enhance the development of these babies to help them fulfil their potential.”

HElPING TINY SURGICAl PATIENTSREACH THEIR FUll POTENTIAl

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WHY WE NEED ClINICAl TRIAlS IN CHIlDRENWe assume that medication given to us is safe, tested and applicable for its use. However a historical lack of paediatric clinical trials means this is often not the case in children.

Children have a different physiology to adults, which means at different ages, they process drugs differently. That is why it is just as important to test the effects of medicines in children as it is in adults, to make sure we are using treatments that will be effective for them, at the right dose and the right time.

One of the challenges with paediatric research is the reluctance of parents and clinicians to test new drugs and treatments on children, because of their vulnerability. But also – thankfully - there simply aren’t always enough sick children in Australia to be able to run the size trials we need to obtain reliable scientific results.

For example, every year there are 40,000 adults diagnosed with cancer in NSW, but only about 200 children. The only way to get the numbers we need is to network with other centres in Australia and internationally to run trials across multiple sites.

New legislation in the United States and Europe now requires all new drugs to be tested in children. That means running paediatric clinical trials has suddenly become big international business.

KRI is at the forefront of establishing a vibrant clinical trials network. As well as the more-than-100 trials we currently have running through The Children’s Hospital at Westmead, we are a founding member of the Paediatric Trials Network Australia, which brings together researchers from around the country to run multi-centre clinical trials in children.

fAMIlY-bASED THERApY A pHENOMENON IN THE TREATMENT Of ANORExIAA clinical trial of children and adolescents with anorexia nervosa has clearly shown that treatment involving the family results in a much speedier and fuller recovery.

The theory is that the family is better placed than any dietitian or psychotherapist to help their child. With the family’s help, many of the young people involved in the trial have recovered in six to 12 months.

“The psychiatric and psychological community see psychotherapy as the treatment of choice, and some people add medication. We don’t believe that’s true,” said Head of the Department of Adolescent Medicine and Eating Disorders, Dr Sloane Madden.

“In particular for children and adolescents, we have shown that, with initial support for nutritional recovery, a family-based treatment approach is much more effective.”

RObERT bOOY: ClINICAl TRIAlS TO pREvENT INfECTIOuS DISEASESClinical trials are central to the work of professor Robert booy, who, as the Head of the Clinical Research team at the National Centre for Immunisation Research and Surveillance (NCIRS), specialises in understanding infectious diseases.

NCIRS conducts clinical trials to study the effectiveness both of vaccines in development and those that have already been registered for use in the community. The main focus is on diseases with high rates of mortality and morbidity such as influenza, meningococcal disease, whooping cough, pneumococcal disease, varicella and dengue.

A particular interest of professor booy is influenza. The pivot study looked at influenza immunisation in day care centres, where children are at increased risk of infection, and its results will be used to inform policy makers about the safety and effectiveness of vaccinating children in this age group.

New vaccines which target four different strains of influenza have been evaluated, as has a vaccine that is given via the skin rather than the muscle. NCIRS has also followed up children who received influenza vaccines at The Children’s Hospital at Westmead to study any adverse events such as fever and convulsions.

Recently professor booy has been involved in vaccine trials for emerging viruses such as dengue fever in queensland and Ross River fever along the eastern seaboard. He has also evaluated vaccines against the deadly meningococcal b strain and the burden of disease it causes, to inform decisions internationally regarding approval for use of new b vaccines.

ClINICAl TRIAlS – MAKINg A DIffERENCEOnly a fraction of the clinical trials conducted in Australia test drugs on children, meaning much of the time doctors have no choice but to use adult medications in children. We are at the forefront of a push to increase the number and quality of paediatric clinical trials in this country, so that we improve the level of evidence for how to best care medically for our children and young people.

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OuR gENE THERApY TRIAl: 14 YEARS Of pREpARATIONAn important gene therapy trial for children with brain tumours is now open at KRI. It aims to overcome one of the biggest problems for cancer patients, that chemotherapy drugs are also highly toxic to the bone marrow.

The trial will involve removing some of the child’s bone marrow cells, then genetically modifying them in the laboratory and putting them back into the child before he or she starts chemotherapy. The trial is a first step in testing this strategy. In the longer term, it is hoped that the gene modification will protect the bone marrow from the harmful effects of the chemotherapy drugs.

Before they could get the trial off the ground, researchers from the Children’s Cancer Research Unit (CCRU), the Oncology Department and the Gene Therapy Research Unit (GTRU) first had to meet regulatory requirements governing clinical trials, including human research ethics approval and approval from the Therapeutics Goods Administration (TGA).

In addition, they needed to find a company to formulate one of the key agents used in the trial in facilities that were up to the standard required to make drugs for use in humans.

“It has taken us 14 years of preparation, progressively overcoming the many challenges that accompany translational research, to get to this point,” said head of the CCRU, Associate Professor Jennifer Byrne.

ClINICAl TRIAlS – MAKINg A DIffERENCE

Clinical Trials week was held in May to promote clinical trials. Twenty-eight industry representatives networked with KRI researchers, while children decorated “hands” which were stuck to boards to show their support for research. The week gave research staff the opportunity to engage with parents about research and clinical trials.

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fOR fIvE OR SIx pER CENT Of CHIlDREN WITH CYSTIC fIbROSIS, THEIR DISEASE IS CAuSED bY A gENETIC MuTATION THAT fAIlS TO OpEN A pORE IN THEIR CEllS AND pREvENTS THEIR luNgS fROM WORKINg pROpERlY. A TRIAl Of A NEW DRug HAS SHOWN THAT IT IS vERY SuCCESSful IN REvERSINg THAT DEfECT.

Most children with cystic fibrosis are born without the pore (known as “CfTR”) altogether, but in a small group the pore exists but it does not open. A blood test shows which patients have the particular genetic mutation that causes the problem.

This failure of the pore to open affects the lungs, upper airways, sinuses, gastrointestinal tract, liver and pancreas. As well as lung function impairment, it causes problems for digestion, the sinuses and the liver – and could explain why children with cystic fibrosis develop other illnesses like diabetes and liver disease.

A new drug called Kalydeco® (ivacaftor), developed by vertex pharmaceuticals and the uS Cystic fibrosis foundation, cures the defect by opening the pore. It has been trialled for the last few years in patients internationally, including through KRI, and the results have been impressive.

“We knew within two weeks who was on the active medicine and who wasn’t – it was quite remarkable,” said Dr Karen McKay of Respiratory Medicine Research.

“This drug is suitable only for five or six per cent of patients, but it does provide hope we can actually come up with compounds that will fix other basic defects in cystic fibrosis.”

Economic modelling has shown that is highly cost effective. using a drug like Kalydeco to improve the category of lung disease from moderate to mild can save more than $22,000 per patient per year, said Dr McKay.

Angela was one of the Australian patients who responded very well to Kalydeco. During the trial, her lung function improved dramatically and she gained 7 kg.

Now she is excelling at two disciplines that would normally be very difficult for a child with a chronic lung disease: sprint and distance running and playing the flute (which she started playing as part of her physiotherapy routine).

“She has always been very sporty and active and she would do quite well, coming second or third. This year she’s winning everything,” said her mother, Ruth.

“but her real passion is music. Now she’s more confident, she loves performing and she can really put herself out there.”

CYSTIC FIBROSIS: TOWARDS A CURE

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IAN AlExANDER: THE ExCITING POSSIBIlITIES OF GENE THERAPY It has never been more exciting to be involved in biomedical research, said professor Ian Alexander, the Head of the gene Therapy Research unit (gTRu).

Our knowledge about and ability to diagnose the genetic causes of disease has exploded in recent years. However our capacity to treat these problems has not yet caught up.

gene therapy aims to address this gap. It uses genes as medicine – repairing faulty genes and replacing them in the patient to eliminate the cause of their condition.

“There has never been a time where the power of genetics is more exciting; more pervasive and opening so many profound possibilities for us. Our aim now is to translate this into better outcomes for children,” said professor Alexander.

His focus is on disorders that affect the liver and bone marrow. He has already achieved remarkable success in using gene therapy to cure mice with urea cycle deficiency (an inherited metabolic disorder) and is now working toward replicating the breakthrough in humans.

He is also involved in two major gene therapy trials, one to reduce the toxicity of chemotherapy drugs in cancer patients, and the other to fix the genetic cause of SCID x1 (the “boy in the bubble” disease).

“Many of the impediments to our success are technological. If we can overcome the basic technological problem of transferring the genes back into the body, a plethora of opportunities will open up. It’s not just one or two diseases that have the potential to be cured – it’s a whole host.”

gERAlDINE O’NEIll: SOPHISTICATED TECHNOlOGY TO WATCH HOW CANCER CEllS SPREADMany brain tumours are hard to treat because their cells spread throughout the brain. Cancer biologist Associate professor geraldine O’Neill, of the Children’s Cancer Research unit (CCRu), is using advanced microscopy techniques to understand this process.

She is observing the cancer cells in special gels which mimic the three dimensional environment and structure of the brain.

The cells’ movement is analysed using KRI’s new correlative light and electron microscopy (ClEM) suite. The new confocal microscope in the ClEM suite allows Associate professor O’Neill and her team to optically section the gel to provide a very detailed picture of how the cells behave.

“There is almost no cure for invasive cancer – I see it as one of the major challenges for which we don’t yet have solutions,” she said.

“A recent advance in cancer research is the understanding that the tissue that surrounds the tumour really impacts on the progression of the tumour cells to become invasive.”

Her work has shown that the cells feel the tissue next to them to determine whether it is hard or soft. That information is relayed inside the cell to change the expression of different genes. This knowledge could one day lead to the ability to change the gene expression – and prevent the cancer cells from spreading.

fRONTIER MEDICINETechnology has revolutionised medicine for children, and opened possibilities that would have been unthinkable just a few years ago. Many of our researchers at KRI are at the forefront of medical discovery, with new findings that will change the world.

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IN A NEW DISCOvERY THAT COulD HElp MANY THOuSANDS Of CHIlDREN AROuND THE WORlD, RESEARCHERS AT KRI HAvE IDENTIfIED A NEW DISORDER THAT MAY ExplAIN WHY SOME CHIlDREN SuDDENlY DEvElOp MOvEMENT AND pSYCHIATRIC pROblEMS.

Antibodies are produced by the immune system and are essential to fight off infection. However, sometimes the immune system gets it wrong and antibodies attack the brain.

After years of research, Associate professor Russell Dale and Dr fabienne brilot-Turville, of the Institute for Neuroscience and Muscle Research (INMR), have identified a new kind of antibody that binds to an important protein in the brain, called dopamine 2 receptor, which controls movement, emotion and behaviour.

Dr brilot-Turville has developed a test to detect the antibody against dopamine-2 receptor. “We use an in vitro system enabling us to detect antibodies against the protein as it would be present in the brain,” she said.

“That could enable doctors to diagnose the cause of the children’s symptoms and use immune therapy to remove the antibody and allow them to recover.”

The antibody is also present in children with chronic conditions such as Tourette Syndrome and Obsessive Compulsive Disorder, opening exciting possibilities for future treatments in those who have an autoimmune cause of their disorders.

Already, a few children have been treated successfully to remove the antibodies.

One of them is Natalia, who came to The Children’s Hospital at Westmead when she was three after nearly two years of unsuccessful tests and treatments for her balance problems.

“At two she would be running and try to stop, and instead of stopping she would fall over,” said her mother, beti.

“She’d lose her balance whenever she got sick and then she’d get better again. but when she was three she had a major relapse and lost the ability to walk. She just couldn’t stand up, the whole room was spinning around her.”

Associate professor Dale put Natalia onto oral steroid treatment and intravenous immunoglobulin. Within a few months her symptoms were completely gone, and 18 months later there is still no sign of the antibody in her blood.

“It was just amazing to watch the transformation,” said beti.

At the moment this test is only available in Dr fabienne brilot-Turville’s laboratory, but it is hoped that the test will be available globally in the future.

A WORlD FIRST DISCOvERY FOR CHIlDREN WITH AUTOIMMUNE DISORDERS

Over the past 12 months, KRI has experienced an increase in the number of work experience students from around Western Sydney and has continued to build relationships with a number of partners including the University of Sydney, University of Western Sydney, University of Technology and local TAFEs.

We continue to enjoy our close affiliation with the Discipline of Paediatrics and Child Health and the Schools of Public Health and Bioengineering at the University of Sydney. The University of Sydney is a leader in medical education and KRI takes pride in high quality research and supervision for all our students.

In 2011, 106 PhD, Masters and Honour students were supervised across the Hospital. They provide an interesting mix, with students involved not just in medicine, but also in health sciences, engineering and allied health research projects.

This year, KRI hosted the University of Sydney Summer Scholarship program with 17 students enrolled across all disciplines. The program was celebrated onsite when the Dean of Medicine announced the most outstanding student, Andrian Yang, who chose to do his placement with the Royal North Shore Hospital.

In second place it was a tie with Sarah Kim who did her placement with the ANZAC Research Institute and Sophie Hale who did her placement with KRI under the supervision of Dr Nicholas Wood.

MICHAElA KREISSl, INSTITuTE fOR NEuROSCIENCES AND MuSClE RESEARCHMichaela’s phD involves looking at mutations in the tropomyosin gene, an important structural muscle protein responsible for regulating muscle contraction.

As part of her studies, she recently travelled to the vu university Medical Centre in Amsterdam to learn their sophisticated techniques to examine the mechanics of muscle contraction.

Michaela developed a new technique to extract muscle fibres from patient biopsies, then freeze them, take them to the Netherlands and thaw them in a way that did not destroy their function. She then used the vu’s equipment to look at the function of the fibres.

Through her work, Michaela has discovered that when tropomyosin is reduced in patients, it interacts less efficiently with the alpha-actinin protein in the muscle, causing muscle weakness. It also becomes less sensitive to nerve stimuli. It is possible that one day this could be modified with medication.

HAYlEY SMITHERS-SHEEDY, CENTRE fOR pERINATAl INfECTION RESEARCHResearchers suspect that congenital cytomegalovirus (CMv) may be an under-recognised cause of cerebral palsy, however this causal pathway has not been studied thoroughly.

Hayley, who also works on the Australian Cerebral palsy Register, is sifting through available data to gauge how much of the burden of cerebral palsy can be attributed to congenital CMv.

findings to date indicate that children with cerebral palsy that is caused by CMv infection tend to be much more severely disabled than those who do not, she said. However many children with cerebral palsy are never tested for CMv.

for that reason, Hayley will also retrospectively screen neonatal guthrie cards for CMv – which hold babies’ blood from a heal prick a few days after birth to see if further links between CMv and cerebral palsy can be established.

STuDENTS AT KRIAt KRI we take our support of students very seriously. We aim to help them through their early careers to build a strong cohort of paediatric researchers for the future. We are in a unique position in that the doctors supervising the research students are generally also clinicians treating sick children on the wards.

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gIllIAN bluE, KIDS HEART RESEARCHgillian’s phD literally spans the laboratory bench to the bedside in the quest to understand the genetic causes of congenital heart disease.

gillian is using sophisticated exome sequencing to find new genes. She is then trying to develop a diagnostic tool to identify the possible genetic causes of CHD in children – which has until now proved problematic because so much congenital heart disease is caused by environmental as well as genetic factors.

The last part of her research will involve finding ways to deliver the information to parents. Since so many children with congenital heart disease are now growing up to adulthood, it is becoming ever more important to refer them for genetic counselling so they have an understanding of the likelihood they have of passing the condition onto their own children.

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STREAM 1 NEUROSCIENCES AND MENTAl HEAlTH We turn basic research – like gene discovery, research into what causes disease and development of new treatments into improved patient care and better health outcomes.

Institute for Neuroscience and Muscle Research (INMR): Professor Kathryn North

Department of Adolescent Medicine and Eating Disorders: Associate Professor Michael Kohn, Dr Sloane Madden

Children’s Hospital Education Research Institute (CHERI): Dr Belinda Barton

Developmental Cognitive Neuropsychology Research Unit (DeCog): Ms Suzanne Benson

STREAM 2 TISSUE ENGINEERING AND BONE REPAIRWe study how the body heals, with the aim of speeding up recovery and promoting healing in children with bone and tissue damage.

Orthopaedic Research and Biotechnology Unit (ORBU): Professor David little

Children’s Hospital Burns Research Institute: Professor Andrew Holland, Associate Professor John G Harvey

STREAM 3 CANCER CONTROlAs one of Australia’s leading paediatric cancer centres, our research aims to improve understanding of cancer and develop new treatments, as well as to test the safety and efficacy of new cancer drugs in clinical trials.

Children’s Cancer Research Unit: Associate Professor Jennifer Byrne

Clinical Oncology Research Unit: Dr luciano Dalla-Pozza

STREAM 4 GENETICS, GENE THERAPY AND GENOMICSWe aim to understand the biology of genetic disorders and use gene therapy to treat genetic conditions in children by replacing faulty genes with healthy ones.

Western Sydney Genetics Research Program: Professor John Christodoulou

Gene Therapy Research Unit: Professor Ian Alexander

STREAM 5 OBESITY, METABOlISM AND NUTRITIONOur research aims to prevent and treat complications resulting from disorders of the metabolism, such as diabetes, osteoporosis and obesity.

Institute of Endocrinology and Diabetes: Professor Kim Donaghue, Professor Geoffrey Ambler

Obesity Research Group: Professor louise Baur

Children’s Hospital Institute for Sports Medicine (CHISM): Dr Robert Parker

STREAM 6 RENAl MEDICINE AND TRANSPlANTATIONOur work aims to improve the quality of life for children with kidney disease by understanding its genetic basis, finding new treatments, developing new methods of diagnosis and studying the prevalence and impact of kidney disease in the community.

Centre for Kidney Research (Clinical): Professor Jonathan Craig

Centre for Kidney Research (laboratory): Associate Professor Stephen Alexander

STREAM 7 INFECTIOUS DISEASE AND IMMUNOlOGYOur work focuses on the immune system and ways of preventing infectious diseases, particularly through immunisation.

Centre for Perinatal Infection Research: Professor Cheryl Jones

National Centre for Immunisation Research and Surveillance (NCIRS): Professor Peter McIntyre, Professor Robert Booy

Department of Allergy and Immunology: Associate Professor Alyson Kakakios

OuR RESEARCH

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STREAM 8 ClINICAl SCIENCE AND HEAlTH SERvICES DElIvERYResearch across this stream aims to provide an evidence-based approach to improving the way we treat sick children.

Australian Paediatric Surveillance Unit (APSU): Professor Elizabeth Elliott

Neonatology and the Grace Centre for Newborn Care Research Unit: Professor Nadia Badawi, Associate Professor Kaye Spence

Respiratory Medicine Research (Children’s Chest Research Centre): Professor Peter van Asperen, Dr Karen McKay, Associate Professor Hiran Selvadurai

SIDS and Sleep Apnea Research: Professor Karen Waters

Department of Adolescent Medicine: Professor Katherine Steinbeck, Associate Professor Susan Towns

Kids Rehab: Dr Stephen O’Flaherty

Kids Heart Research: Associate Professor David Winlaw

Kids Critical Care Research Unit: Dr Marino Festa, Dr Jonathan Egan

Emergency Medicine Research Group: Dr Mary McCaskill

Anaesthesia and Pain Research: Associate Professor David Baines

Department of Nuclear Medicine: Professor Robert Howman-Giles

Centre for Trauma Care, Prevention, Education and Research: Professor Danny Cass

Nursing Research and Practice Development Unit: Professor valerie Wilson

Centre for Evidence-Based Paediatrics, Gastroenterology and Nutrition: Professor Elizabeth Elliott, Dr Diana Thomas

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30

OuR fINANCESOPERATING STATEmENT AT 30 JuNE (uNAudITEd) 1

2011/12 $000

2010/11 $000

REvENuE fROM SOuRCESResearch Grants 13,410 12,868

Donations and other Contributions 5,539 5,938

Infrastructure Support 2 2,456 2,151

Block Funding 3 1,611 1,178

Investment Income 1,020 1,050

TOTAl REvENuE 24,036 23,185

ExpENDITuRE ON OpERATIONSEmployee Related Expenditure 16,342 15,249

Goods and Services 7,433 7,122

Repair, Maintenance and Renewals 389 415

Depreciation 1,133 1,438

TOTAl ExpENDITuRE 25,297 24,224

RETAINED SuRpluS / (DEfICIT) (1,261) (1,039)

RESOuRCE AllOCATION ($000)REvENuE

ExpENDITuRE

56% – Research Grants, $13,410

23% – Donations and other Contributions, $5,539

10% – Infrastructure Support, $2,456

7% – Block Funding, $1,611

4% – Investment Income, $1,020

65% – Employee Related Expenditure, $16,342

29% – Goods and Services, $7,433

4% – Depreciation, $1,133

2% – Repairs, Maintenance and Renewals, $389

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OuR fINANCESBALANCE SHEET AT 30 JuNE (uNAudITEd) 1

2011/12 $000

2010/11 $000

CuRRENT ASSETSCash at Bank and Investments 29,238 29,312

NON-CuRRENT ASSETSInvestments 4,760 4,772

Buildings 4 18,436 18,354

Plant and Equipment 1,869 2,007

NET ASSETS 54,303 54,445

REpRESENTED bYAccumulated Funds 52,883 53,494

Revaluation Reserve 2,681 1,990

Retained Surplus / (Deficit) (1,261) (1,039)

RETAINED EquITY 54,303 54,445

Notes:

1. Kids Research Institute is the research division of The Children’s Hospital at Westmead which forms part of The Sydney Children’s Hospitals Network (Randwick and Westmead). Separate financial statements are not audited for the Kids Research Institute. The consolidated annual audited financial statements of The Sydney Children’s Hospitals Network (Randwick and Westmead) are available on request or you can visit our website at www.schn.health.nsw.gov.au

2. Infrastructure support has been provided by The Children’s Hospital at Westmead.

3. Block funding has been provided by NSW Ministry of Health to (1) the National Centre for Immunisation Research and Surveillance; (2) Paediatric Tumour Bank and (3) GTRU-VECTOR Production Facility.

4. The buildings of The Children’s Hospital at Westmead is owned by Health Administration Corporation and administrated by The Sydney Children’s Hospitals Network (Randwick and Westmead). The estimated value of buildings recognised in the balance sheet is based on the floor space occupied by Kids Research Institute.

RESOuRCE AllOCATION ($000)ASSETS

54% – Current Cash & Investments, $29,238

34% – Buildings, $18,436

9% – Non-Current Investments, $4,760

3% – Plant & Equipment, $1,869

32

The Kids Research Institute is the research centre of choice for many paediatric health researchers.

We attract some of the best because of our world-class laboratories, equipment and support, coupled with direct access to one of the largest and most significantly diverse paediatric health populations anywhere in the world through The Children’s Hospital at Westmead.

but we cannot continue our work without your support.

While research projects are funded primarily through competitive grants from government bodies and donations from organisations, we rely on the generosity of donors to provide vital services and equipment to enable the researchers to conduct their research.

For every $100 provided directly for specific research projects through grants and donations, we need to raise an additional $28 to provide all the necessary equipment, maintenance and specialised support services to undertake research. This equates to over $3.5 million every year.

Your support is critical to the success of our mission – to give all kids the opportunity of a happy, healthy life, both today and for generations to come.

Thank you.

TO MAKE A DONATIONMail Fundraising Department Kids Research Institute at The Children’s Hospital at Westmead locked Bag 4001 Westmead NSW 2145

Cheques should be made payable to The Children’s Hospital at Westmead.

Phone 02 9845 3367

Online www.kidsresearch.org.au

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The Children’s Hospital at Westmeadlocked Bag 4001Westmead NSW 2145(02) 9845 1400www.kidsresearch.org.au