Funded Programs Clinical

Slowing the Progression of Cognitive Decline in Alzheimer\'s Disease Using Mifepristone (RU486) Investigator(s): Joseph K. Belanoff, MD, CEO; Alan F. Schatzberg, MD, Professor and Chair of Psychiatry Institution(s): Corcept Therapeutics, Inc., Menlo Park, CA; Stanford University, CA

Summary:
Excessive levels of stress hormones such as cortisol damage the brain and may contribute to the development of Alzheimer’s disease. Reducing levels of cortisol or blocking its effect may be useful in treating AD. Mifepristone (RU486) is a glucocorticoid antagonist (blocker) that blocks plasma cortisol activity and has been shown to improve cognition in patients with psychosis. Corcept Therapeutics, Inc. (Corcept), a small biotechnology company based in California, believes that mifepristone may be useful in treating AD. In collaboration with Dr. Alan Schatzberg at Stanford University, Corcept plans to carry out a double blind, placebo controlled Phase IIa study. Seventy patients will receive either mifepristone or placebo over a six-month period in which cognitive and laboratory tests (including plasma cortisol) will be carried out. The aim is to determine if mifepristone improves memory or delays progression in AD. Positive results in this study will provide the basis for additional clinical studies.

Public Attitudes Towards Genetic Testing in Alzheimer\'s Disease Investigator(s): Peter J. Neumann, ScD, Assistant Professor Institution(s): Harvard School of Public Health, Boston, MA

Summary:
Advances in genetic testing will open up the possibility of early detection of Alzheimer\'s disease. The availability of this information will offer new choices about whether to obtain such information and what to do with it once acquired. There are also concerns about the impact of genetic testing results on health costs and the consequences of health insurance companies and employers gaining access to test results. This study involves carrying out a national survey to understand attitudes and concerns about genetic screening for AD. The survey will address the following questions: 1) what % of Americans will take a genetic test which indicates the likelihood of developing AD later in life; 2) how do responses vary with age, gender, race, family history of AD; and 3) how much would individuals pay for such information. The data will help inform policy makers on the issue and be useful in formulating informed consent, pre-test counseling and medical insurance policies.

A Phase I Study of Nerve Growth Factor Ex Vivo Gene Therapy for Alzheimer\'s Disease Investigator(s): Mark H. Tuszynski, MD, PhD, Associate Professor of Neurosciences Institution(s): University of California, San Diego, CA

Summary:
Dr. Tuszynski proposes to determine the feasibility of using gene therapy to administer NGF to the cholinergic neurons of the basal forebrain in a small number of patients in the early stages of Alzheimer’s disease. Their novel technology involves altering skin cells taken from the patients themselves to produce NGF and then placing these cells into the affected brain regions to determine if they can continue to produce NGF. By using the patient\'s own skin cells, the investigators hope to eliminate the rejection that is commonly associated with transplantation. The primary outcome will be safety. Secondary outcome measures will determine if the treatment improves cognitive function.

Randomized, Double blind Clinical Study of Ampalex (CX516) in patients with Mild Cognitive Impairment Investigator(s): Steven A. Johnson, Ph.D., Head of Biological Science Institution(s): Cortex Pharmaceuticals, Inc., Irvine, CA

Summary:
This grant will fund a pilot clinical study to determine the effects of a novel compound Ampalex (CX516) in elderly patients with mild cognitive impairment (MCI). Cortex Pharmaceuticals, a small biotechnology company based in California, has developed a class of novel compounds that promote the activity of a glutamate receptor called AMPA. Ampalex (CX516) is the lead compound from Cortex\'s drug development program. The compound may have the added advantage of increasing production of brain molecules such as nerve growth factor (NGF) and brain-derived growth factor (BDNF).

Indole-3-Propionic Acid (OXIGON™) in Alzheimer\'s Disease Therapy Investigator(s): Daniel Chain, PhD, Chief Executive Officer and Chief Scientist Institution(s): Mindset BioPharmaceuticals, Jerusalem, Israel

Summary:
Antioxidants may prevent or delay the progression of Alzheimer’s disease. However, new, more effective antioxidants are needed. Vitamins E and C penetrate the brain poorly and are metabolized in the body to compounds that are pro-oxidant. Mindset is developing a compound called OXIGON™, a naturally occurring molecule reported to be a powerful antioxidant which efficiently crosses the blood brain barrier and is not metabolized to pro-oxidants. In addition, OXIGON™ has been shown to interact with the amyloid protein and to prevent conversion to the aggregated toxic form of the molecule that causes damage in AD. Thus, OXIGON™ has a unique dual action that is expected to block two important pathogenic mechanisms in AD, the formation of toxic amyloid fibrils and damaging free radicals. These pre-clinical and clinical studies will establish the safety of OXIGON™ in animals and humans, and determine appropriate dosing in human Phase I clinical trials.