June 30, 2000 -- There is currently no treatment to slow disease progression in patients with Huntington's disease, the devastating hereditary brain disorder that killed folk-singer Woody Guthrie and afflicts some 30,000 Americans.
Victims' mental and physical abilities degenerate, leading to dementia, and they lose control of their movements and eventually die. But animal studies from Harvard University's Brigham and Women's Hospital offer hope that sufferers will soon have a weapon to help them fight the disease -- one that has been around for the last 30 years.
Mice bred as models for Huntington's lived 14% longer when treated with the common antibiotic minocycline, the July issue of the journal Nature Medicine reports. Harvard researchers say they will soon begin human trials of the antibiotic in patients with Huntington's disease.
"If the human safety trials go well, we should be able to recommend this for Huntington's patients within the year," study author Robert M. Friedlander, MD, tells WebMD. "Our studies showed that there were more minocycline side effects in the Huntington's mice compared to normal mice. This could pose a problem, but I don't think it will translate to humans."
If the antibiotic appears safe and effective in patients with Huntington's, Friedlander suggests it might be taken daily by those who know they will develop the disease, beginning perhaps five to 10 years before symptoms appear. Children who have a parent with Huntington's have a 50% chance of also developing the disease, and symptoms generally first develop between the ages of 35 and 45. A genetic test has been available since 1993.
"This is all hypothesis, because we have no human data at this point," Friedlander says. "What is real is that today there is no drug treatment for Huntington's. This is a very good candidate for a treatment, not a cure."
Friedlander and other experts say the antibiotic could be the first in a series of advances bringing the management of Huntington's out of the Dark Ages. They envision a drug cocktail approach similar to that now being used to treat AIDS patients, in which different agents target different mechanisms of this complex disease.
"I think the importance of this study is not necessarily that this drug will be useful in humans, although it may turn out to be, but it shows that drug compounds can potentially be helpful," says Christopher Ross, MD, PhD, who was not involved with the study.
"This drug by itself may not have a huge impact, but if you can get two or three drugs acting in different ways, the cocktail might be quite effective," says Ross, professor of psychiatry and neuroscience at Johns Hopkins University and chair of the Medical and Scientific Advisory Committee of the Huntington's Disease Society of America (HDSA).
HDSA spokeswoman Joyce Hammel agrees. "This is very exciting, because it is the first time we have seen anything delay the onset of disease and increase life expectancy in an animal model," she tells WebMD. "We are hoping that several discoveries like this will result in a synergistic approach to the cure of HD." The cocktail approach appears the most likely, she says, even though there is only one gene that causes the disease, because there is a very complex progression from the gene to actual cell death and symptoms.
Huntington's disease is caused by a genetic disorder that prompts nerve cell death in the region of the brain that controls movement. A little over a year ago, Friedlander and colleagues reported that an enzyme called caspase-1 is activated in the brains of humans and mice with the disease, and that blocking caspase function delays disease onset and mortality in mice. The Harvard researchers used minocycline in their most recent studies because it is known to inhibit caspase-1 and caspase-3.
The antibiotic was found to significantly slow Huntington's disease progression in the mouse model, but Friedlander says it is not yet clear why. "We don't exactly know why minocycline works, but it is not the antibiotic effect," he says. "We believe there are other properties involved, but we don't know what they do."
While he agrees the findings are exciting, Ross would not speculate on when an effective therapy might be available for the treatment of Huntington's disease. "I am very hopeful that we will soon see some sort of therapy, but I wouldn't want to say when," he says. "We still have a lot to learn."
- Huntington's disease is a genetic disorder that causes progressive mental and physical degeneration, eventually resulting in death.
- Researchers have found that the antibiotic minocycline slows the progression of Huntington's disease in mice, but they are unsure how it works.
- Trials in humans are expected to begin soon, and researchers hope treatments will become available that may be used before the onset of symptoms in those who know they will develop the disease.