1. 1. Slowing the Progression of Alzheimers Disease Using Gene Therapy Jos Enrique Ros-Castillo RISE Program Prof. Enrique Rodrguez-Borrero, Ph.D
2. 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. 3. Areas affected by AD
4. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
16. 16. Any Questions or doubts?