Dr. Robert Friedlander Labpage

06/27/00- Updated 04:45 PM ET

Antibiotic may help fight Huntington's

WASHINGTON (AP) - An antibiotic used to treat a variety of infections may one day offer hope to people suffering from the inherited and deadly Huntington's Disease, if experiments in mice also work in humans.

An estimated quarter-million Americans suffer from the currently untreatable disorder in which the brain degenerates, gradually reducing the person's ability to walk, talk and reason.

But researchers at Brigham and Women's Hospital in Boston and Harvard Medical School report that they were able to slow the progress of the disease in mice by using the antibiotic minocycline. Their findings appear in the July issue of the journal Nature Medicine.

''We're very excited about this,'' said Dr. Robert M. Friedlander, lead researcher. He said he expects minocycline will eventually become part of a cocktail of several drugs in treating Huntington's Disease.

''I think this is an important study,'' added Dr. Christopher Ross of Johns Hopkins University in Baltimore, who was not part of the research team. ''They have a new drug which can be given orally ... which can slow the progression of the disease in this mouse model. I think that's very much a reason for hope.''

But minocycline must first be tested for toxicity in humans, Friedlander cautioned, noting that the drug appeared slightly more toxic in mice with their form of Huntington's Disease than it did in normal mice.

Minocycline is a form of tetracycline currently used in humans to treat acne, rheumatoid arthritis and other diseases. Unlike the better known tetracycline, minocycline can cross the blood-brain barrier that blocks most chemicals from entering the brain.

In the brain, minocycline blocks the production of some of the enzymes called caspases that cause brain cells to commit suicide. Production of caspases in adult brains has been associated with Huntington's Disease, Lou Gehrig's Disease, Parkinson's Disease and strokes, Friedlander said.

Caspases help eliminate unneeded cells in the developing fetus. But victims of Huntington's Disease inherit a gene that causes changes in the brain, usually beginning in middle age, that include the activation of caspases.

Friedlander previously succeeded in delaying the onset of Lou Gehrig's Disease in mice using a different chemical to inhibit the action of caspases.

After a 1998 study found that minocycline reduced the size of the injury following a stroke by limiting caspases, Friedlander decided to see if it had affect in Huntington's.

''Since we found evidence that caspase-1 plays a role in the progress of HD we decided to test the drug and it worked,'' Friedlander said. ''It prolonged the life of the mice, which was the most important thing.''

But, he said, the mice eventually went on to die, indicating that the disease is complex and this was treating only one part of it.

But, he said he believes that minocycline will become part of a set of drugs useful in battling the disease, just as several drugs are now used in combination against AIDS.

In the new paper, Friedlander's team reports that minocycline blocks the production three of the enzymes that appear to be involved in the progression of the of Huntington's Disease, caspase-1, caspase-3 and inducible nitric oxide synthase (iNOS).

Blocking iNOS uncovered a new part of the mechanism causing the disease, said Ross, who heads the medical and science advisory council of the Huntington's Disease Society of America.

The enzyme iNOS helps produce nitric oxide, a source of free radicals than can damage cells, providing ''the first really direct evidence'' that oxidants and stress have a significant role in Huntington's, Ross said.