NEW YORK (Reuters Health) - Early results from a phase I clinical trial of nerve growth factor (NGF) gene therapy for Alzheimer’s disease show a reduction in cognitive decline and an increase in cortical metabolic activity after treatment, investigators report in the April 24th online issue of Nature Medicine.
“These data from the first human trial of growth factor gene delivery for Alzheimer’s disease are intriguing and provide a clear rationale for continuing with this program,” Dr. Mark H. Tuszynski from the University of California, San Diego said in a telephone interview with Reuters Health.
In the study, autologous fibroblasts genetically modified to express human NGF were implanted in the forebrain of eight patients with early mild Alzheimer’s disease. The procedure was initially performed while the subjects were awake but slightly sedated. However, two subjects moved as the cells were being injected causing subcortical hemorrhage and one died five weeks later, prompting a switch to general anesthesia.
The six subjects who completed the NGF gene delivery procedure safely and were followed for a mean of 22 months, experienced a 37% to 51% reduction in the rate of cognitive decline as measured by standard cognitive tests. “If that effect holds up in subsequent larger placebo-controlled trials, it will substantially exceed the effectiveness of current therapies for Alzheimer’s disease,” Dr. Tuszynski said.
Postoperative PET scans in four subjects showed a significant (p < 0.05) increase in cortical glucose uptake after treatment. “This is a biological marker of cortical activity and confirms what one would predict based on the biology of these growth factors in animal studies.” Dr. Tuszynski noted.
Moreover, say the investigators, brain autopsy of the patient who died suggested “robust growth responses to NGF.”
A second phase I trial is now underway and 4 of 6 patients have been treated so far, according to Dr. Tuszynski. In this trial, investigators are using an adeno-associated virus vector. Results could be available by the end of this year.
Source: Nature Med 2005. [ Google search on this article ]
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