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New Alzheimer’s Drug Shows Success In Halting Disease Progression

Posted on: Wednesday, 30 July 2008, 16:34 CDT

An experimental Alzheimer’s drug shows promise in halting progression of the disease through a new approach of dissolving the protein tangles that form in victims’ brain.

The results were announced Tuesday at a Chicago medical conference, and came as welcome news to an industry besieged with recent setbacks.

The drug, called Rember, was developed by Singapore-based TauRx Therapeutics.

But even if larger, more comprehensive tests prove Rember works, it would still be several years before the drug is available as a treatment for Alzheimer’s patients. 

Nevertheless, conference goers were excited about the initial results.  

"These are the first very positive results I've seen" for stopping mental decline, Marcelle Morrison-Bogorad, director of Alzheimer's research at the National Institute on Aging, told the Associated Press.   

The National Institute on Aging had funded early-stage research into the tangles, which consist of a protein called tau that builds up in the brain’s neurofibers and leads to dementia.

"It's just fantastic," Morrison-Bogorad added.

Alzheimer’s disease afflicts more than 26 million people worldwide, a number only expected to grow as the population ages.

For years, researchers had focused, without success, on a different protein called beta-amyloid, which forms sticky clumps outside of the cells.

Rember is currently in the second of a three-stage development process, and scientists are particularly interested in potential treatments due to the enormity of the illness.  The four Alzheimer's treatments currently on the market merely ease symptoms of the disease.

Claude Wischik, TauRx's CEO and also a biologist at the University of Aberdeen in Scotland, has long performed critical research on tau tangles as well as studies that show Rember can dissolve them.

An "esteemed biologist", Wischik’s research "comes with his credibility attached to it", according to Dr. Sam Gandy of Mount Sinai School of Medicine in New York, who leads the Alzheimer’s Association’s scientific advisory panel.

In the latest study, 321 patients received one of three doses of Rember or a placebo capsule three times daily.   The capsules containing the highest dose had a flaw in formulation that prevented them from working, while the lowest dose was too weak to prevent worsening of the disease, Wischik told the AP.

But interestingly, the middle dose was effective as measured by a broadly used score of mental performance.

"The people on placebo lost an average of 7 percent of their brain function over six months whereas those on treatment didn't decline at all," Wischik said.

The researchers found that after about a year, the placebo group had continued to decline, whereas those on the mid-level Rember dose had not.  At 19 months, the treated group had still not declined.

Wischik said two types of brain scans were available on about 30 percent of the study participants, and they revealed the drug was active in brain areas most impacted by tau tangles.

"This is suggestive data," not proof, Wischik cautioned.

The company is working to raise additional funding for another test next year.

Rember’s main chemical is currently used in a different formulation in the prescription drug methylene blue, sometimes used for chronic bladder infections.  However, since it became available in the 1930’s, the medication predates the U.S. Food and Drug Administration and was never fully tested for safety and effectiveness.  Furthermore, it was not reviewed in the form used in the Alzheimer's study, Wischik warned.

At the International Conference on Alzheimer's Disease on Monday, other researchers announced promising results of tests of a different experimental drug that also targets tau tangles. That drug, made by British Columbia-based Allon Therapeutics Inc., was studied in those with mild cognitive impairment, a precursor to Alzheimer's.

The tau-drug test results stand in sharp contrast to the disappointing results of Flurizan, a drug aimed at blocking the enzymes that form beta-amyloid clumps.   Myriad Genetics announced in June that it would discontinue development of Flurizan as a result of the failure.  The full results of that study were presented at Tuesday’s conference.

Comprehensive results from a separate closely watched test of bapineuzumab were also reported.   Bapineuzumab is an experimental drug that uses the body’s immune system to dissolve the sticky brain clumps.  The drug’s developers, Wyeth and Elan Corp. PLC, had previously reported that a 240-patient study failed in its goal of enhancing patients' mental performance at 18 months.

But despite the disappointing results, bapineuzumab seemed to help the roughly 60 percent of study participants without a gene that researchers believe worsens the severity of Alzheimer's disease.  Those results underscore the company's claims of potential effectiveness in some patients. 

However, concerns about possible side effects surfaced after twelve cases of a type of brain swelling occurred in those on bapineuzumab, while none occurred in the placebo group.  While the swelling caused few if any symptoms, outside experts said it may have played a role in other side effects, which were two or four times more prevalent in patients on bapineuzumab than in those receiving a placebo.  

For instance, anxiety was reported in 11 percent of those taking bapineuzumab, compared with only 4 percent taking the dummy drug.  Paranoia occurred in 7 percent of bapineuzumab users, versus only 1 percent of those on the placebo.  High blood pressure, vomiting, weight loss, and back pain were also reported in the study.

Among the 124 patients taking bapineuzumab, three deaths occurred, but were not related to the drug, according to Dr. Sid Gilman of the University of Michigan, who led the study's data safety monitoring board.   Two deaths were attributed to worsening Alzheimer’s disease, and one was due to pneumonia.

Elan and Wyeth have previously said they will conduct late-stage testing of bapineuzumab in more than 4,000 patients.

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On the Net:

• National Institute on Aging
• Alzheimer's Association

Source: redOrbit Staff & Wire Reports

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