Drug’s Effect Questioned by Alzheimer Researchers

Teams of researchers in this country and abroad have failed so far to confirm a California psychiatrist’s controversial finding that patients with Alzheimer’s disease who received the experimental drug THA experienced “dramatic” improvement.

Researchers from Canada and Sweden reported at a symposium this weekend preliminary findings of what one called “small but measurable improvement.” And a group from the Sepulveda Veterans Administration Medical Center reported no measurable change and potentially serious side-effects.

“We found no dramatic response,” said Dr. L. Jaime Fitten of UCLA and the veterans medical center. “We had to work pretty hard to fish out some subtle changes.”

Widespread public interest in THA was aroused in November, 1986, when the New England Journal of Medicine published an article by Dr. William K. Summers of Arcadia stating that THA had dramatically improved the memory and living skills of a small number of patients.

Conclusions Questioned

Summers’ study came under immediate fire from other researchers who questioned his techniques and conclusions. The U.S. Food and Drug Administration reported in January that it, too, had found numerous shortcomings in the work.

Summers, however, maintains that his basic findings are valid. He has accused the agency of nit-picking. He and his supporters suggest that Summers is being persecuted because he is an independent researcher bucking the academic establishment.

During the weekend, researchers from as far away as China took part in what was said to be the first symposium devoted exclusively to drug therapy for Alzheimer’s, the degenerative brain disorder that is now the fourth leading cause of death among the elderly, afflicting about 2.5 million Americans.

That number is expected to increase dramatically in coming decades as the proportion of elderly in the population increases. Yet researchers know little about the disease and there are no known cures, treatments or methods of prevention.

“Before, people were very skeptical,” Dr. Ezio Giacobini, an organizer of the symposium at the Southern Illinois University School of Medicine, said of the idea of discussing drug therapy for Alzheimer’s. “I think THA has changed the attitude. It has made people more optimistic, even if we don’t have the answer.”

The symposium focused on a class of drugs that inhibit a particular enzyme in the brain that breaks down an important chemical, acetylcholine. That chemical, which plays a crucial role in memory, is believed to be deficient in Alzheimer’s patients.

Much of the discussion centered on THA, or tetrahydroaminoacridine, and a related drug, physostigmine. But other experimental therapies were also considered, including the use of certain nerve gases as well as substances isolated from a Chinese herb and from Caucasian snowdrops.

Among the numerous researchers working with THA in hopes of verifying Summers’ findings, Dr. Serge Gauthier of Quebec, Canada, said preliminary findings of small improvement in some of his 51 patients left him “cautiously optimistic.” He also reported serious side-effects but said they appeared to be reversible.

But Fitten reported “no dramatic improvement in cognition or functional capacity” in the 10 patients he studied late last year. Furthermore, he said, the drug elevated liver enzymes in three patients to 10 times their normal levels.

Study Resumed

That particular side-effect put a brief halt to a nationwide trial of THA sponsored in part by the U.S. government. That study, the largest so far, resumed in January using lower doses and is expected to yield preliminary findings within a year.

Asked how he thought THA had emerged from the two-day conference, Summers said, “slightly smudged.” He said he was encouraged by the Canadian and Swedish findings and not worried about Fitten’s.

One of the difficulties in studying Alzheimer’s and possible treatments is the variability of the disease among patients, researchers said. They also acknowledged that traditional psychometric tests may fail to pick up small improvements in behavior.

Conflicting Results

Some researchers stressed the importance of observations by relatives living with the patients. Others, however, cautioned that family members’ perceptions may be muddied by wishful thinking.

Dr. Rodger Elble, a neurologist at Southern Illinois University, noted in an interview that many drugs have produced conflicting results in early trials. He said the drug L-dopa, once pronounced useless by some scientists during early trials, is now used widely to treat Parkinson’s disease.

“I think this is a valid approach,” Elble said of the drugs being tested for Alzheimer’s. “The effects have been very small and very variable. I think we should look at this realistically.”