Groundbreaking Alzheimer's Gene Therapy Trial Moves Ahead
A therapy that could halt -- and possibly reverse -- the dementia caused by Alzheimer's disease is entering the second phase of scientific trials on human subjects. Participants will receive injections of a genetically engineered virus through tiny holes drilled in their skulls. The hope is that the virus will encourage lifelong production of nerve growth factor.
Tests of a promising new gene therapy to treat Alzheimer's disease are moving to the phase II level, bringing the reversal of dementia damage one step closer to becoming a real medical possibility.
Developed by scientists in The Memory Disorders Program at Georgetown University, CERE-110 is a virus engineered with the gene encoding nerve growth factor (NGF). The virus is injected directly into the affected parts of the brain through holes surgically drilled into the patient's skull. The virus is then used by the nerve cells to manufacture the NGF protein from the NGF gene.
"The goal is to boost NGF production in the brain, thus restoring health and function to diseased nerve cells and preventing them from dying," R. Scott Turner, MD, PhD, director of Georgetown's Memory Disorders Program, told TechNewsWorld.
The benefits from a single application could conceivably last a lifetime.
"We suspect that NGF production will be increased for the rest of the patient's life, but this will be confirmed at eventual autopsy," explained Turner.
The success of CERE-110 could help millions of people worldwide and dramatically reduce healthcare costs for aging populations. The worldwide societal cost estimate for dementia is US$315.4 billion, based on a worldwide prevalence estimate of 29.4 million people with dementia, reported scientists at the 4th Conference of Alzheimer's Disease International.
For at least the last 15 years, the majority of people with dementia worldwide have been living in developing regions of the world. They already account for more than 60 percent of all healthcare cases, according to the ADI, and by 2040, this proportion will have risen to 71 percent.
Dementia affects 1 in 20 people over the age of 65 and 1 in 5 over the age of 80. Worldwide, there are an estimated 30 million people with dementia. By 2050, the ADI estimates the number will rise to more than 100 million.
First Trial of Its Kind
The results from CERE-110 animal studies and a Phase I human trial look "very promising," said Turner. Those results are grounds for testing in human subjects with Alzheimer's disease in the new Phase II study.
"This is our first study of a gene therapy injected into [the] brain, and thus the trial requires close collaboration with our neurosurgery colleagues at GUMC -- in particular Dr. Chris Kalhorn," said Turner.
Kalhorn, an associate professor of the department of neurosurgery at Georgetown University Hospital, routinely performs neurosurgical procedures similar to the one being utilized in this study, noted Turner.
About 50 people with Alzheimer's disease will participate in this study at fewer than 10 hospitals nationwide. Only persons with early stage Alzheimer's disease, who are evaluated and deemed competent to consent for themselves, will be permitted to participate in the study. All patients in the study will undergo surgery to drill two small holes in the skull. Only those patients randomly assigned to receive CERE-110 will have genes injected into the brain. Those subjects randomized to the placebo group will not have the genes injected.
"Neither the treating physicians nor the patients will know until the end of the study who actually received the treatment," explained Turner. This is standard testing procedure, called a 'double-blind study' designed to prevent accidental biased or false results.
The study is sponsored by the Alzheimer's Disease Cooperative Study (ADCS) through a grant from the National Institute on Aging, in association with Ceregene, which will provide the active agent used in this study. Georgetown University Medical Center will be reimbursed for the costs of performing the study by the ADCS. Turner, the study's lead investigator at Georgetown, has no financial interests to disclose, he said.