The document discusses using gene therapy to slow the progression of Alzheimer's disease. It proposes using an experimental drug called CERE-110, which contains the gene for human nerve growth factor (NGF), to restore degenerated neurons in the brain affected by Alzheimer's. The methodology involves surgically injecting CERE-110 into the nucleus basalis of the brain in 25 human subjects with mild to moderate Alzheimer's. It is expected that the NGF will be produced, protecting neurons from further degeneration and potentially reducing symptoms and slowing disease progression.

1. Slowing the Progression of
Alzheimer’s Disease Using Gene
Therapy
José Enrique Ríos-Castillo
RISE Program
Prof. Enrique Rodríguez-Borrero, Ph.D

2. Alzheimer’s 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 Alzheimer’s
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 Alzheimer’s 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 it’s 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 Alzheimer’s 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 Alzheimer’s 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
<http://www.ncbi.nlm.nih.gov/pubmed/20373268>

16. Any Questions or doubts?