November 4, 2005


By ROBIN LORD
STAFF WRITER

WOODS HOLE - Two Woods Hole researchers, using a naturally occurring drug and a common sea slug, have shown promising results with memory that may have implications in the treatment of Alzheimer's.

Marine Biological Laboratory researcher Alan Kuzirian works with sea slugs in his Woods Hole laboratory.

Alan Kuzirian and Herman Epstein, researchers at the Marine Biological Laboratory, conducted a yearlong study using the compound bryostatin to improve memory in Hermissenda sea slugs. They collaborated with Dr. Daniel Alkon of the Blanchette Rockefeller Neurosciences Institute in Rockville, Md., who used white mice with the same results.

The research results, recently published in the Proceedings of the National Academy of Sciences, suggest bryostatin may stimulate the production of proteins in cells essential for long-term memory.

''Bryostatin has the potential to reduce the onset of Alzheimer's disease,'' Kuzirian said in an interview at his MBL office.

The drug has not yet been tested on humans.


A progressive disease

Alzheimer's disease is a progressive brain disorder that gradually destroys a person's memory and ability to learn, according to the national Alzheimer's Association. It primarily strikes late in life, with the risk doubling every five years after age 65.

Alzheimer's stats Research on the enzyme bryostatin, which was given to sea slugs at the MBL, shows potential for use in treating Alzheimer's. 8,500 Alzheimer's cases on Cape Cod and the islands during the 2000 Census After age 65 The risk of being diagnosed with Alzheimer's doubles every five years

Cape Cod and the islands, where more than 20 percent of the population is over 65, have the highest incidence of the disease in the state, said Cathy Pastva, executive director of Alzheimer Services of Cape Cod and the Islands, an educational and support organization. The 2000 Census figures showed that about 8,500 people on Cape Cod, Martha's Vineyard and Nantucket suffer from the disease.

The results of Kuzirian's, Epstein's and Alkon's work is exciting, Pastva said, because it shows bryostatin may enhance the brain's ability to put down new memory, which is something no other drug can now do.

But Christopher Novak, a member of the Alzheimer Services board and a pharmacist, said it is too soon to pin too many hopes on the drug, since it has not been through clinical trials on humans. But if bryostatin can be shown to actually target the underlying disease process involved in Alzheimer's, he said, it would be a huge breakthrough, since all current drugs treat only the symptoms of the disease.

Early Alzheimer's patients typically cannot store new long-term memories. The researchers' work with the small brown sea slugs demonstrated that bryostatin biochemically enhances this ability. They found noticeable differences in the ability of the slugs to retain the memory of a training exercise after bryostatin was introduced.

Kuzirian has used Hermissenda for many of his experiments during his 26 years at MBL. He refers to them as ''white mice of the sea.''

In this latest study, which began in the spring of 2004 and ended this summer, Kuzirian and Epstein used a technique using light and agitation of the water surrounding the slugs. Sea slugs withstand wave action by contracting their ''foot'' to cling to something, like the bottom of a boat. They also are sensitive to light.


Memory tests

The two scientists conducted the experiment by putting the sea slugs in separate sections of a small Lucite tray. Then they would turn on a light and shake the tray, forcing the slugs to respond. When the animals developed a conditioned response by automatically contracting their foot when the light turned on, the researchers looked to see how long the memory would last.

Kuzirian and Epstein found that by injecting carefully controlled doses of bryostatin into the water, the slugs would retain the memory of the conditioned response longer.

Bryostatin also has the ability to activate protein kinase C, or PKC, a group of enzymes that plays a pivotal role in cell signalling systems. Bryostatin is already used in cancer therapy because in high doses it inhibits PKC and triggers cancer cells to die, Kuzirian said.

But when bryostatin is used in small, regulated doses, it activates PKC, promoting cell growth in the portion of the brain where memory is stored, Kuzirian said.

How does a small sea creature's learning ability have application for the human brain? Neural networks used for light and balance are basically the same in all animals, Kuzirian said. Researchers use the Hermissenda slug because of its ability to learn associations between stimuli has ''striking parallels to human learning,'' he said.

The positive effects of bryostatin on memory were also shown on mammals through Alkon's work at the Blanchette Rockefeller Neurosciences Institute. He demonstrated that bryostatin helps mice learn a maze more quickly.

Scientists believe there may be several abnormalities at work in the brain of an Alzheimer's patient. One is the accumulation of amyloid plaques, clumps of protein that attach to the brain's nerve cells. Alkon's study with mice also showed that bryostatin has the potential to reduce the onset of Alzheimer's by inhibiting the aspect of PKC that causes the harmful type of amyloid plaques to form in the brain, Kuzirian said.

Robin Lord can be reached at rlord@capecodonline.com.

(Published: November 4, 2005)