Antibodies, drug, exercise provide Alzheimer’s hope

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A “passive” vaccine against Alzheimer’s, a drug designed to filter out brain-clogging proteins and inhaled insulin may all offer ways to treat Alzheimer’s disease in the future, new research shows.

No single treatment showed dramatic effects, and certain patients with Alzheimer’s benefited more than others - which suggests the disease may need to be fought on several fronts, they told a prevention conference sponsored by the Alzheimer’s Association.

Dr. Marc Weksler and colleagues at the Weill Medical College of Cornell University in New York tested an old remedy for a range of diseases called intravenous immunoglobulin or IVIg. It is a pooled preparation of immune system proteins called antibodies taken from healthy donors.

Evidence suggests that the body produces antibodies against the abnormal proteins that destroy the brains of Alzheimer’s patients, but for some reason some people cannot make enough.

Weksler’s team gave IVIg to eight patients with mild to moderate Alzheimer’s over six months.

It was a phase I study, designed only to show the treatment was safe. “But we were really quite surprised that patients did really quite remarkably,” Weksler told a news conference.

Six patients showed an improvement in their ability to think, and none of the patients deteriorated, as might be expected.

Weksler said Baxter International was trying to develop an antibody that specifically targets the abnormal beta amyloid 42 protein that causes the worst initial brain damage in Alzheimer’s. Such a product could be patented, unlike IVIg, and might work better, too, he said.

SNIFFING INSULIN

Suzanne Craft of the University of Washington School of Medicine and colleagues tested inhaled insulin in Alzheimer’s patients, based on studies that show administering insulin directly to the brain can help improve thinking in people who are impaired.

In this study, only a specific group of patients did better on a memory test afterward - those with Alzheimer’s who do not have a genetic mutation called APOE-4 that is known to put people at higher risk of the disease.

People with normal brain function and Alzheimer’s patients with the mutation, about half the group, were not helped by the inhaled insulin. Precise dosing may be key, Craft said.

In another study, Dr. Gordon Wilcock of the University of Bristol in Britain tested a new drug being developed by Myriad Genetics Inc. called Flurizan.

The company has already reported some disappointing results from the phase II clinical trial but Wilcock says he sees hope for the drug, known generically as (R)-flurbiprofen.

Flurizan targets gamma secretase, an enzyme key to making normal beta amyloid protein into the dangerous kind that clogs the brain and kills neurons.

It did not initially seem to improve memory or cognition much in more than 200 patients. “The moderate subjects didn’t seem to benefit,” Wilcock said. But patients with mild disease did.

And when they sorted out the patients who seemed to absorb the drug the best, they found this group had 50 percent less deterioration over a year, keeping memory and day-to-day function better than patients given a placebo.

Wilcock said this helps researchers figure out who might benefit from treatment, which was the aim of the study. Other studies have suggested the need to treat Alzheimer’s early, before too many brain cells are destroyed by the disease.

Myriad has started phase III studies.

A Chinese study showed a combination of herbs helped patients with mild cognitive impairment, which can develop in Alzheimer’s, while a study done in Japan showed benefits from a very mild exercise-and-singing program.

As many as 25 million people globally may have dementia, and those numbers will rise as the population ages. 

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