In this year’s blockbuster Rise of the Planet of the Apes, a scientist reverses his father’s Alzheimer’s disease with a simple shot in the arm. The cure was temporary. But not entirely far-fetched.
Canadian scientists are working on an intravenous treatment for Alzheimer’s that could halt the progression of the disease and improve cognitive functions – without the risk of a mass ape revolt.
Vancouver researcher Neil Cashman and colleagues have discovered a biomarker on toxic molecules called amyloid-beta (a-beta) oligomers, which are catalysts in the brain degeneration of Alzheimer’s.
Their industry partner, Cangene Corp., a Winnipeg-based biopharmaceutical company, is developing antibodies designed to attack the toxic molecules without harming healthy ones.
If their work is successful, the antibodies could be used as an immune therapy for Alzheimer’s, or as a preventive vaccine, says Dr. Cashman, scientific director of PrioNet Canada, a network of centres conducting research into neurodegenerative disorders.
“We believe that we’ve found a target – perhaps the target – for treatment of Alzheimer’s disease,” he says.
Alzheimer’s is a neurodegenerative disorder, not an immune disease. Nevertheless, the immune system can be harnessed to defend against the harmful molecules involved in Alzheimer’s, says Dr. Cashman, a specialist in neurological diseases at the University of British Columbia.
He and other researchers at UBC and the University of Sherbrooke have found that selected antibodies will attack a-beta oligomers in cultured nerve cells. “It renders them non-toxic,” he says.
The next step is to test the treatment on mice engineered to develop Alzheimer’s. Mice studies will be completed at UBC and a lab in Milan, Italy, likely within three months, Dr. Cashman says.
If the work goes as planned, Cangene will begin developing an experimental treatment for clinical trials in humans, he says. “Cangene thinks it’s four years away.”
Immunotherapy for Alzheimer’s is a “very promising approach,” says Paul Aisen, a professor of neurosciences at the University of California, San Diego. But because various types of molecules may be involved in causing the disease, he says, “it’s not clear which precise targets are going to prove most useful.”
Alzheimer’s researchers have been testing different forms of immune therapy for some time. About a decade ago, Elan, a biotechnology company headquartered in Dublin, conducted human trials in the San Francisco Bay area using a vaccine against a-beta molecules. The trials were cut short in 2002 because 6 per cent of the patients developed meningoencephalitis, an inflammation of the brain that resulted in several deaths.
At the time, researchers concluded that the vaccine activated the immune system’s T cells, which attacked a-beta molecules in healthy nerve tissue.
But Dr. Cashman and his colleagues are developing a treatment that will target only a-beta oligomers, using the marker he has found. A-beta oligomers are widely accepted as a main source of neuron-harming toxicity in Alzheimer’s disease, he says.
Recent findings by other researchers suggest that immunotherapy may be a viable treatment, Dr. Cashman says. He points to human trials funded by Baxter International at institutions including the New York-Presbyterian Hospital/Weill Cornell Medical Center. In the multiphase trials, researchers are testing antibodies prepared from the blood of healthy plasma donors, known as intravenous immunoglobulin (IVIG), on patients with mild to moderate Alzheimer’s. “They’re getting remarkable results,” Dr. Cashman says.
In April, 2010, Baxter released unpublished findings of a phase II study showing that patients with Alzheimer’s who received IVIG had less brain atrophy and better cognitive functioning after 18 months compared with patients in a control group.
The Baxter trials are taking what some researchers call a “kitchen sink” approach to immunotherapy, giving patients a blood product containing all available human antibodies in hopes that some will be of benefit.
Instead, Cangene will select specific antibodies to develop an IVIG product with a “more concentrated effect,” Dr. Cashman says. Given Baxter’s success using unselected IVIG, he adds, “I think it’s actually going to work.”
But others are skeptical, and several Canadian specialists declined to comment on such early research.
Dr. Aisen cautions against jumping to conclusions based on the success of Baxter’s phase II study. Since only 14 patients received the full course of IVIG, the evidence that immunotherapy can halt Alzheimer’s is “too preliminary,” he says.
Dr. Aisen was not involved in the phase II trial, but he and colleagues at Alzheimer’s Disease Co-operative Study are conducting Baxter’s phase III trials using IVIG. The team has recruited 380 patients with mild to moderate Alzheimer’s for the third study, which is set for completion in about a year. Although the phase II results are encouraging, he says, “we really want to see the results of the larger study.”
In the meantime, Dr. Aisen suggests that lab experiments on cultured nerve cells and mice provide little evidence that a cure for Alzheimer’s is on the horizon.
“It’s a long way from a cell culture study to a human treatment,” he says.Report Typo/Error