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Gene Therapy for Alzheimer's Disease Clinical Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00017940
Recruitment Status : Completed
First Posted : June 22, 2001
Last Update Posted : December 11, 2009
Institute for the Study of Aging (ISOA)
University of California, San Diego
Information provided by:
National Institute on Aging (NIA)

Brief Summary:
This Phase I clinical trial is the first step in testing gene therapy. This study is called a "Safety/Toxicity" study by the Food and Drug Administration, and primarily aims to determine whether the experimental protocol is safe for humans. It will determine whether the study procedure causes side effects in humans, and may also give us a preliminary sense of whether this will be effective in combating Alzheimer's disease in humans.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Genetic: Human Nerve Growth Factor Phase 1

Detailed Description:

Although the precise pathogenesis of AD is unknown, certain pathological features accompany the disease. These pathological features include the abnormal accumulation of extracellular amyloid, the formation of intraneuronal neurofibrillary tangles, synapse loss, and cellular degeneration. Cellular degeneration occurs in several neuronal populations in the central nervous system. Among the neuronal populations that degenerate in AD, loss of basal forebrain cholinergic neurons is particularly severe. Loss of cholinergic neurons in AD correlates best with severity of dementia, the density of amyloid plaques in the brain, and the amount of synapse. To date, the only FDA-approved therapies for Alzheimer's Disease focus on augmenting the function of degenerating cholinergic neurons.

The present trial will move beyond compensating for cholinergic neuronal degeneration by attempting to 1) protect cholinergic neurons from degeneration, and 2) augment the function of remaining cholinergic neurons by directly elevating choline acetyltransferase (ChAT) function in neurons. These two therapeutic interventions will be brought about by the delivery of human NGF to the brain.

NGF has been shown to prevent both lesion-induced and spontaneous, age-related degeneration of basal forebrain cholinergic neurons. Further, NGF infusions reversed both lesion-induced memory loss and spontaneous, age-related memory loss in rodents. Based on these findings, NGF administration offers significant potential as a neuroprotective strategy in Alzheimer's disease.

Grafts of primary fibroblasts transduced to express human nerve growth factor have been shown to sustain NGF in vivo gene expression for at least eighteen months in the rodent central nervous system. In addition, these grafts sustain NGF messenger RNA production for at least 14 months in vivo. In primate systems, ex vivo NGF gene therapy has been demonstrated to sustain NGF protein production in the brain in the rhesus money for at least one year.

Thus, the available data suggests that ex vivo NGF gene therapy is an effective means of preventing loss of basal forebrain cholinergic neurons and of augmenting cholinergic function in the primate brain. In animals, this procedure is safe and well tolerated. Based on these data, clinical trials of ex vivo NGF gene therapy in Alzheimer's disease has begun.

This is an 18 month, open label, prospective Phase I clinical trial of Ex Vivo Gene Therapy for Alzheimer's disease in 8 patients with a mild degree of cognitive impairment. Patients will be screened for the diagnosis of Probable Alzheimer's disease of mild severity. After obtaining informed consent, three skin biopsies will be obtained to generate cultures of primary, autologous fibroblasts. These cells will be cultured, then genetically modified to produce and secrete the human nerve growth factor (NGF) molecule. If fibroblasts are deemed acceptable based on NGF production rates and standard cell culture sterility tests, then patients will receive intracerebral injections of their own primary fibroblasts into the region of basal forebrain cholinergic neurons in the brain, where neurons are undergoing atrophy as a result of Alzheimer's disease.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 8 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Ex Vivo Nerve Growth Factor Gene Therapy for Alzheimer's Disease
Actual Primary Completion Date : November 2003
Actual Study Completion Date : November 2003

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Neurologist certified diagnosis of probable Alzheimer's disease
  • Early stage of Alzheimer's disease (generally within three years of onset)
  • Normal speaking ability and normal ability to understand
  • Ability to understand the potential risks of participation in this study
  • Willing to visit the San Diego area and be available for many visits in the first year
  • Willing to discontinue use of drugs Cognex, Aricept, Exelon, or Reminyl for the first 18 months of the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00017940

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United States, California
University of California, San Diego, ADRC
La Jolla, California, United States, 92037
Sponsors and Collaborators
The Shiley Family Trust
Institute for the Study of Aging (ISOA)
University of California, San Diego
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Principal Investigator: Mark Tuszynski, MD, PhD University of California, San Diego
Publications of Results:
Other Publications:
Layout table for additonal information Identifier: NCT00017940    
Other Study ID Numbers: IA0029
First Posted: June 22, 2001    Key Record Dates
Last Update Posted: December 11, 2009
Last Verified: July 2005
Keywords provided by National Institute on Aging (NIA):
Gene Therapy
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action