Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00017940
Status:
COMPLETED
Last Update Posted:
2009-12-11
First Post:
2001-06-20
Brief Title:
Gene Therapy for Alzheimers Disease Clinical Trial
Sponsor:
The Shiley Family Trust
Organization:
National Institute on Aging NIA
Study Overview
Official Title:
A Phase I Study of Ex Vivo Nerve Growth Factor Gene Therapy for Alzheimers Disease
Status:
COMPLETED
Status Verified Date:
2005-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This Phase I clinical trial is the first step in testing gene therapy This study is called a SafetyToxicity 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 Alzheimers disease in humans
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 Alzheimers 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 Alzheimers 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 Alzheimers disease has begun
This is an 18 month open label prospective Phase I clinical trial of Ex Vivo Gene Therapy for Alzheimers disease in 8 patients with a mild degree of cognitive impairment Patients will be screened for the diagnosis of Probable Alzheimers 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 Alzheimers disease
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 Alzheimers 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 Alzheimers disease has begun
This is an 18 month open label prospective Phase I clinical trial of Ex Vivo Gene Therapy for Alzheimers disease in 8 patients with a mild degree of cognitive impairment Patients will be screened for the diagnosis of Probable Alzheimers 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 Alzheimers disease
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None