1. Slowing the Progression of Alzheimers Disease Using Gene
Therapy Jos Enrique Ros-Castillo RISE Program Prof. Enrique
Rodrguez-Borrero, Ph.D
2. Alzheimers Disease Alzheimer's disease is a progressive
condition that destroys the connections between cells in the brain.
Eventually these cells die, which affects how the brain works. As
cells die in the outer layer of the brain, it shrinks, and the
spaces in the brain get larger. The cortex includes the
hippocampus, which is an area of the brain that helps new memories
form. The damage to the brain eventually causes problems with
memory, intelligence, judgment, language, and behavior. Alzheimer's
is the most common form of mental decline, or dementia, in older
adults.
3. Areas affected by AD
4. What is Gene Therapy? Gene therapy is designed to introduce
genetic material into cells to compensate for abnormal genes or to
make a beneficial protein. If a mutated gene causes a necessary
protein to be faulty or missing, gene therapy may be able to
introduce a normal copy of the gene to restore the function of the
protein.
5. Nerve Growth Factor (NGF) NGF is a protein that promotes
survival, differentiation, and process extension of selected
neuronal populations during development and, in some cases, in the
mature organisms. Previous lesion and aging studies in the rat have
shown that intracerebroventricular NGF infusions can prevent
degenerative changes in basal forebrain cholinergic neurons.
6. CERE-110 Experimental biopharmaceutical drug designed to
restore damaged cholinergic cells and protect them from further
degeneration. Consists of a vector containing only the gene for a
human nerve growth factor. This drug will serve as a carrier for
delivering a NGF to the brain cells.
7. Hypothesis Using the CERE-110 drug for the transportation of
nerve growth cells to the inside of the brain to restore
degenerated neurons and protect them will stop or slow down the
progression of Alzheimer's disease.
8. Logistics Before beginning with the tests, a drug testing
permit is needed because the drug will be administered on human
subjects. This permit is required to legally test the drug on human
beings.
9. Methodology 1. I will select around 25 human subjects that
have Alzheimers disease at a mild or moderate stage. By selecting
this quantity of patients, I will be able to analyze the
effectiveness of CERE-110. 2. Locate the nucleus basalis, which is
a group of neurons in the brain rich in acetylcholine that are
affected by AD. 3. CERE-110 will be surgically injected into the
nucleus basalis of the brain using a stereotactic injection.
10. Methodology 4. CERE-110 enters the neuron, inducing it to
produce a continuous lifetime supply of NGF. 5. The human subjects
brain activity will be monitored to observe the effectiveness of
the drug. 6. Laboratories and other clinical procedures will be
made to evaluate the progressiveness of the disease.
11. Future Investigations and Work CERE-110 will be studied to
test the potential benefits, safety, and make sure that it does not
have negative effects. If it proves to be successful against
Alzheimers disease, it will be distributed across hospitals around
the world for benefit of people who carry this disease.
12. Potential Pitfalls The drug does not reach its destination
in the brain. CERE-110 reached the destination but the nervous
system rejects it.
13. Expected Results NGF is expected to restore the function of
the neuron and protect it from further degeneration, hence
potentially reducing the severity of symptoms and slowing disease
progression.
14. References: Nerve Growth Factor Study. Regents of the
University of California, 2008. Retrieved July 1, 2015 from
www.adcs.org. http://adcs.org/studies/ngf.aspx Areas of the Brain
Affected By Alzheimers and Other Dementias. WebMD, LCC, 2005.
Retrieved July 1, 2015 from www.webmd.com.
http://www.webmd.com/alzheimers/areas-of-the-brain-affected-
by-alzheimers-and-other-dementias NGF and the Treatment of
Alzheimers Disease. Olson L, 2000. Retrieved June 30, 2015 from
www.ncbi.nlm.nih.gov.
http://www.ncbi.nlm.nih.gov/pubmed/8282080
15. References Gene Therapy. Lister Hill National Center of
Biomedical Communications, June 2015. Retrieved June 30, 2015 from
www.ghr.nlm.nih.gov. <
http://ghr.nlm.nih.gov/handbook/therapy?show=all > CERE-110,
Gene Delivery Vector Expressing Human Nerve Growth Factor for the
Treatment of Alzheimer's Disease. Mandel, RJ, April 2010. Retrieved
June 30, 2015 from www.ncbi.nlm.nih.gov