1
GM2 Gangliosidoses GM2 gangliosidoses are a group of lysosomal lipid storage disorders caused by mutations in at least 1 of 3 recessive genes (HEXA, HEXB, and GM2A), resulting in accumulation of GM2 ganglioside substrate inside neuronal lysosomes, leading to cell death. Research Goal: Understand the patient’s and caregiver’s perspective of living with late- onset GM2 gangliosidosis (Tay-Sachs disease and Sandhoff disease). Patients’ Experience & Perspective Patient and Caregiver Experience with Late-Onset Tay-Sachs and Sandhoff Diseases Alaa Hamed 1 , Robert N. Krupnick 2 , Julie Kissell 3 , Susan R. Kahn 4 , Swati Sathe 5 , Florian Eichler 6 , and Gerald F. Cox 7 1 Patient Outcomes and Medical Economics, 3 Medical Affairs, and 7 Clinical Development, Sanofi Genzyme, Cambridge, MA, USA; 2 Quintiles, Advisory Services, Cambridge, MA, USA; 4 National Tay-Sachs & Allied Diseases Association, Boston, MA, USA; 5 Department of Neurology, Rutgers New Jersey Medical School, Newark, NJ, USA; 6 Department of Neurology, Massachusetts General Hospital, Boston, MA, USA Results Methods Conclusions The most frequent and impactful symptoms reported (lack of/limited mobility, odd gait, frequent falling, speech changes, etc.) align well with documented literature: In both late-onset Tay-Sachs and Sandhoff disease, patients are often described as “clumsy and awkward”, which is directly in line with how these patients described their balance and frequent falling issues. The patients mentioned experiencing symptoms of frequent muscle tremors, [proximal] muscle weakness, as well as changed speech (slurred speech, talking fast), all of which are cited to be more apparent in the first decade of disease manifestation, indicating underlying neurologic problems. Development of a broad-based ataxic gait that makes walking difficult, and described by these patients as “having an odd walk,” is well documented and leads to patients almost always losing ambulatory ability by the sixth decade of disease. Background and Objectives References: 1. GM2 gangliosidoses – Clinical Summary”, http://www.medlink.com/medlinkcontent.asp; “About Late Onset Tay-Sachs”, http://www.lateonsettay-sachs.org/index.php?p=ct&pgid=7. Acknowledgments: The authors thank Adrienne Aiello, Nate Thibault, and Marianne B. Zajdel (Sanofi Genzyme) for writing assistance and help in the preparation of this poster, and Laurie LaRusso (Chestnut Medical Communications, Walpole, MA) for poster layout. The text and figures in this presentation cannot be reproduced without the explicit permission of the authors and Sanofi Genzyme. Scan for this poster Key Objectives: Explore and understand the symptoms of patients who are living with late-onset GM2, their experience with treatment, and the impact of the disease on their lives. Understand possible differences in experience over time. Understand the impact of providing care and support to the adult patient with late-onset disease from the perspective of the caregiver. Major Topics of Discussion Patients Caregivers Background information in terms of age, living situation, diagnosis and treatment (if any) Symptom frequency and severity experienced as result of their disease Impact of disease symptoms on their lives and those of loved ones. Background information in terms of age, relationship with adult GM2 patient Caregiver’s roles and responsibilities in caring for the GM2 patient Formal training in caregiving and relationship with medical community Impacts and burdens of caregiving Perspective on the impact of the disease on the patient. Project Approach: Adult patients with GM2 (n=12) and caregivers (n=7) were contacted and recruited through their membership in the National Tay-Sachs & Allied Diseases Association (NTSAD). Two patient focus groups and one caregiver focus group were conducted with attendees at NTSAD's 37th Annual Family Conference in Reston, Virginia, April 18, 2015. Patient-reported GM2 symptoms align well with published literature 1 The most common and impactful symptoms can serve as possible trial endpoints These most impactful symptoms present viable opportunities to evaluate in clinical trials for GM2 as possible primary or secondary endpoints: Almost all patients are most frustrated by their lack of/limited mobility as well as their lack of balance and its immediate impact (e.g., broken bones), and categorically expressed desire to improve these symptoms. Research on ways to enable patients to move more independently, especially in moderate to advanced disease stages, would strongly improve patients’ quality of life by enabling them to be mobile and independent for as long as possible. Patients and caregivers alike have strong need for additional support This research highlighted key needs for additional support for both patients and their caregivers: For patients, there is a need for solutions that would enable more independence and management of their own lives for as long as possible. Patients would like to be able to move more, reduce falling, and maintain their ability to communicate. For caregivers, there is a strong need for training, social support, and activities that reduce or help manage their burdens. Many expressed a strong sense of uncertainty about how best to provide care for their patients’ unique needs (e.g., tips, resources), equating it to “having another child, each is different.” Many noted a lack of social outlets to exchange ideas and share experiences, citing the NTSAD conference as a welcomed exception. Caregiver organizations and/or forums that help them learn more about the disease, their roles, and what to expect in the near and long terms (even though disease experience is not formulaic), as well as social opportunities to meet other caregivers, would greatly enhance their lives. Caregivers’ Experience & Perspective Preliminary Conceptual Model of GM2 Concepts Model is based primarily on patient interviews, but uses caregiver input when confirmatory Patient population: Adult patients diagnosed with late-onset GM2 gangliosidoses (Tay-Sachs disease and Sandhoff disease) Disease Process: GM2 gangliosidoses are a group of lysosomal lipid storage disorders caused by mutations in at least 1 of 3 recessive genes: HEXA, HEXB, and GM2A, resulting in accumulation of GM2 ganglioside substrate inside neuronal lysosomes, leading to cell death. Signs/Symptoms of Disease Direct Impact Constant fear of falling Inability to work Financial difficulties Decreased ability to proactively engage in social / family settings Decreased ability to verbally self-express Depression Indirect Impact Bolded concepts are those identified by patients in both groups as most frequent and impactful. Difficulty walking long distance “Clumsy” gait/stride Frequent falling Muscle weakness Speech changes (slurred, fast pace) Abdominal muscle cramps Coughing fits Difficulties chewing and swallowing Dry mouth Fatigue/lack of energy Frequent diarrhea Recurrent pain (legs and full body) Itchy skin Muscle tremors Slow physical reaction time Vertigo / dizziness Broken bones, bruising and spraining (from falling) Difficulty climbing stairs Difficulty communicating verbally Difficulty getting up from chair or after falling Choking Difficulty playing sports Inability to move around independently Inability to perform household tasks Limited ability to care for oneself (showering, dressing, eating, etc.) Who Are GM2 Patients? GM2 patient groups differed greatly by age distribution, time since diagnosis, and living situation. Group 1: older patients who lived with their spouses Group 2: mostly younger patients diagnosed within past 5 years and living alone or with parents Patient Group 1 (n=7) Patient Group 2 (n=5) Age 20 – 39 years old: 29% 40 – 59 years old: 29% 60+ years old: 43% 20 – 39 years old: 60% 40 – 59 years old: 40% 60+ years old: 0% GM2 Disease Variant Tay-Sachs disease: 71% Sandhoff disease: 29% Tay-Sachs disease: 100% Sandhoff disease: 0% Time Since Diagnosis 1 – 5 years: 43% 6 – 10 years: 14% >11 years: 43%* 1 – 5 years: 60% 6 – 10 years: 20% >11 years: 20% † Current Living Situation Living with spouse and family:71 % Living with parents: 0% Living alone: 29% Living with spouse and family: 20% Living with parents: 40% Living alone: 40% Current Management of GM2 None of the patients are currently on medication specifically for GM2 ~50% take medications to manage symptoms (e.g., chronic pain) and comorbidities (e.g., depression) *All three patients were diagnosed >30 years ago. †This patient was diagnosed 24 years ago. Key Symptom Insight Difficulty Walking Long Distance Across all GM2 patients, difficulty walking long distance is one of the most common symptoms. Most patients describe this as feeling of exhaustion when walking, which limits how far they can go. “Clumsy” Gait/Stride Almost all patients express having a “clumsy” or “funny” walk, most since childhood. Consensus is that the odd gait is a result of knees or ankles not being oriented well for easy walking. Frequent Falling All patients frequently lose balance and fall and are often unable to stop themselves from falling because the fall is usually sudden. Those who can still walk have to be constantly watchful because even a small misstep or uneven surface can trigger a fall. Muscle Weakness Muscle weakness, especially in lower body, is among the symptoms all patients experience. Patients often link muscle weakness to falling and inability to walk far because they believe their lower body muscles are too weak to sustain movement. Slurred Speech and/or Too Fast Most patients have seen changes in their speech as a result of their disease. The degree of speech change varies from patient to patient, with some indicating they slur, while some speak too fast. Key Symptoms Lack of Sustained Mobility, “Clumsy” Gait, Falling Problems with limited mobility and “clumsy” gait/stride are common among these GM2 patients. Patients are often unable to walk long distances, have adjusted their strides to accommodate their difficulty with walking, and fall very frequently. Muscle Weakness, Speech Changes Additionally, patients cite muscle weakness and changes in speech as among the most common symptoms. Symptom Experienced by all/ most Experienced by some/only a few Not mentioned at all (even when probed) Patient Group 1 (n=7) Patient Group 2 (n=5) Mostly older patients with longer experience with disease (some >30 years since diagnosis) Mostly younger patients (<60 years old) with shorter experience with disease (most <10 years since diagnosis) Abdominal muscle cramps All patients get abdominal cramps, especially at night. A few patients get abdominal cramps though their experience is not as severe as in Group 1. Coughing fits All patients said they get coughing fits, especially when eating. Difficulties chewing and swallowing Almost all patients mentioned chewing and swallowing difficulties and are often concerned about choking. The oldest patient in the group (56 years old) has difficulties chewing and swallowing, others simply eat slowly and chew thoroughly. Frequent diarrhea Majority experience diarrhea episodes. Vertigo/dizziness A few patients experience dizziness or vertigo (terms used interchangeably) without warning. Recurrent pain (legs and full body) A few patients experience pain in their legs or overall. The oldest patient in the group (56-year-old) experiences systemic pain though not severe. Itchy skin A few patients experience itchy skin all over the body. Dry mouth One patient mentioned dry mouth and having to always carry a drink or gum to prevent it. A few patients get dry mouth, though their experience is not as severe as in Group 1. Fatigue / Lack of energy Most patients say they feel fatigued even when performing small tasks. Muscle tremors Most patients experience muscle tremors that interfere with their dexterity. Slow physical reaction time Most patients mentioned slow muscle reaction time, which makes them accident-prone. Patients’ View of Effects of GM2 on Other People When asked how the disease has affected other people, patients most often express concern that their increased level of reliance on others due to limited/complete lack of mobility impacts other peoples’ interactions with them. They feel their disease is “socially burdensome” to others. Patients’ Increased Reliance on Other People Unable to proactively engage with other people Limited social engagement from other people Many patients, especially younger ones who are most likely going through the transitory period of needing care, say lack of mobility and ability to self-care has increased their reliance on others and negatively affected their social lives. For these patients, the reliance on others to move towards and initiate interactions with them in social/family settings prevents them from being proactive, and it rests the burden on others to engage. Some patients feel that other people do not always make the effort to engage with them because they might be unaware of their difficulties to move, or perceive them to be antisocial. Who Are GM2 Caregivers? Caregivers in this sample are typically close family members (spouses or parents); the majority are employed, live with the GM2 patient, and have been caregivers for more than a decade. GM2 Caregivers (n=7) Age 40 – 59 years old: 43% 60+ years old: 57% Employment Employed (full or part time): 71% Retired: 29% GM2 Disease Variant that Patient Has Tay-Sachs disease: 71% Sandhoff disease: 29% Current Living Situation Living with and caring for spouse patient: 57% Living with and caring for adult child patient: 29% Visits sister frequently to assist with care (patient lives separately): 14% Median Time Since Beginning Caregiving 12 years (range 1 year – 37 years) Impact and Burdens of Caregiving Deep emotional investment in the well-being of the patient, deep uncertainty about the future, and a high level of patient need as the disease progresses combine to create a high level of understated, yet undeniable, stress in the day-to-day lives of these caregivers. Impacts & Burdens Physically demanding Financial strain now and in future Giving up careers and/or social life Anxiety/ stress about safety of patient Fear and uncertainty about the future The progressive nature of GM2 and fear for patient safety creates considerable stress. Unsurprisingly, many frequently sacrifice personal time & growth to meet the needs of the patient. Finances are a huge worry among these caregivers, given how expensive it is to manage the disease over time. Caring for GM2 patients is physically taxing for caregivers, especially in advanced stages when patients are increasingly dependent. Caregivers’ Perspective of GM2 Patients’ Experience When asked how the disease has affected the GM2 patients they care for, caregivers expressed that patients struggle to accept their condition, are anxious about the future, and experience emotional isolation, particularly those with moderate-to-advanced disease. Patient Experience From Caregiver Perspective Reported Behaviors by Caregivers Caregivers believe patients are acutely aware of their limited capabilities and their symptom progression over time. Most patients struggle to accept their disease and experience frustration in their inability to self-care, to help their caregivers in the household, or move independently. Further, even when they do not express it, caregivers believe that the patients they care for are concerned about the future for themselves and their caregivers, particularly around finances and ability to provide physical care. With progression of the disease over time, caregivers note that patients feel increasingly isolated from reduced ability to express themselves or actively engage with others in social situations. Loss of Independence & Reduced Self-Esteem Fear/Uncertainty About the Future Emotional Isolation Disclosures: Alaa Hamed and Julie Kissell are employees of Sanofi Genzyme; Susan Kahn has received grant funding from Sanofi Genzyme; Robert N. Krupnick is an employee of Quintiles and discloses that Quintiles received contracted project fees and expenses for study design, data collection, analysis, and reporting; Gerald F. Cox is an employee of Sanofi Genzyme and owns stock in Genzyme and Sanofi; Swati Sathe and Florian Eichler have nothing to disclose. #LB-10 Scan for all Sanofi Genzyme-sponsored posters
