Newhouse News Service

A drug originally developed for cancer patients is being touted as a possible breakthrough in treatment for Alzheimer’s because it shows effectiveness in attacking both the short- and long-term memory loss that are hallmarks of the disease, according to a new study.

Called bryostatin, the drug was found to stimulate production of specific proteins within the brain required to construct new, long-term memories. This is especially significant because Alzheimer’s patients typically experience problems of memory storage.

“This could be a real breakthrough for Alzheimer’s patients. It’s like putting memory proteins in the brain’s bank for later use,” said lead author Daniel Alkon, scientific director of the Blanchette Rockefeller Neuroscience Institute, which is affiliated with both Johns Hopkins and West Virginia University and dedicated to the study of human memory.

The research by Alkon and his colleagues, who worked with scientists from the Marine Biological Laboratory in Woods Hole, Mass., is being published this week in the online early edition of the journal Proceedings of the National Academy of Sciences.

Alkon said the next step is to convince the Food and Drug Administration to allow human trials to proceed.

Bryostatin, manufactured by Aphios, a biopharmaceutical company in Woburn, Mass., has been studied in trials as a potential treatment for metastatic melanoma, small intestine cancer and kidney cancer. In the Alzheimer’s research, the drug was shown to improve long-term memory in a marine snail, Hermissenda. Alkon said the mollusk was used because the Pavlovian conditioning response is very close to that found in mammals.

The drug was introduced to the mollusk in the days leading up to a learning activity which paired light and orbital shaking resembling ocean turbulence. Giving the drug to the mollusk a day in advance of the conditioning training, as well as on the day of training, resulted in an enhanced memory retention of the response, which was to “briskly cling to a surface” as if trying to hold on.

“If you give this drug in advance, they will remember (the response) for weeks,” he said.

Alkon said from the animal studies, bryostatin may prove to be “the first demonstration of any drug that can give Alzheimer’s patients a head start in being able to retain what they learn.”

“The proteins they need are already there. This drug just turns them on,” he said.

In an earlier study of bryostatin designed to show the neurodegeneration found in Alzheimer’s patients, Alkon and his colleagues used mice that had been genetically engineered to show signs of Alzheimer’s. The drug succeeded in activating enzymes that directly reduced the production of toxic proteins that are abnormally elevated in Alzheimer’s, a disease that affects nearly 5 million Americans.

Alkon said that study, published in the same journal in 2003, proved that bryostatin could not only provide symptomatic relief from memory loss, but also protect against the degeneration of the neurons that are causing it.

But there have been many potential Alzheimer’s drugs over the years that seemed to work in animals and the success did not translate to humans.

“We’ve had a lot of very promising things crop up, but when the rubber met the road, the effects were damaging in humans or it interacted unfavorably with other things,” cautioned R.E. Markin, director of research for the Alzheimer’s Disease Research Foundation.

Markin advised a “wait and see” attitude.

Martin Gizzi, chairman of the New Jersey Neuroscience Institute at JFK Medical Center in Edison, believes the drug may hold promise, however. According to Gizzi, it is the ability to create new connections between brain cells that is important in memory. He said in people with Alzheimer’s, so many neurons have died that there is no opportunity for forming these connections because “the cells simply aren’t there anymore.”

Gizzi said if it turns out bryostatin could actually prevent cell death, it would be getting at the root cause of Alzheimer’s disease, rather than simply enhancing the chemical connections between nerve cells, which he said current medications are already able to do.

“This preventive aspect sounds like something one could take advantage of in early stage Alzheimer’s. Someone with a strong family history may even want it as preventative therapy,” he said.

Angela Stewart writes about health care for The Star-Ledger of Newark, N.J. She can be contacted at astewart@starledger.com.