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Novartis in Deal With Institute

Huntington...s Disease to be Studied with Mass. General Hospital

By Carey Goldberg
THE BOSTON GLOBE

When Todd Bliss was 19 and found out that he almost surely faced the degenerative death sentence of Huntington’s disease, there was no treatment, no cure — nothing even close. Scientists complained that seeking one was like looking for a needle in a haystack.

Then, in 1993, researchers identified the gene for Huntington’s. Bliss was “so overjoyed, you have no idea — it was like landing on the moon.” The discovery was hailed as a scientific landmark, and talk swelled of an imminent cure.

Now, Bliss, of Plainville, Mass., is 45, his Huntington’s has begun to hamper his finer movements, and there is still no cure for the disease, which affects at least 30,000 people in the United States.

He stays resolutely positive and carefully salts away pleasant memories for the dark future when he will be too disabled to do anything but lie in bed and recall them.

But he also takes part in clinical trials of promising treatments, follows the torrent of reports on new research, and dares to believe that, though it may not come soon enough for him, a cure will come in time for his children, if they inherit the disease.

If anything, scientists say, the problem now is not seeking a needle but choosing which of a plethora of needles is most worth pursuing.

So many clinical trials are underway that researchers sometimes have trouble finding enough Huntington’s patients to study. More potential treatments are coming from machines that rapidly test thousands of chemical compounds, looking for the best drugs. And more are stemming from experimental treatments that have dramatically helped mice with the disease.

Now a major drug company is getting into the act: Novartis just signed a deal to collaborate with MIT and Massachusetts General Hospital, home to more Huntington’s researchers than anywhere else.

“We’ve gone from nothing to now kind of having, in a way, too many things,” said Dr. Steven Hersch, a Mass. General Huntington’s disease researcher, who said potential treatments already number in the hundreds. “Right now the emphasis is probably on weeding things out and figuring out which thing within a given category is most potent or has the fewest side effects.”

The hard lesson learned by those with Huntington’s disease and those who research it is: A gene is a great thing to identify, but it’s a long way from a cure. That’s a lesson that many others seeking to crack genetic diseases are learning, too.

“It was complete illusion on everyone’s part that sequencing the genome would give us the answers” to cure many genetic diseases, said Dr. Mark C. Fishman, president of the Novartis Institutes for Biomedical Research, the company’s research arm, which is headquartered in Cambridge. “The genome gives us the words. We still do not have the grammar for drug discovery until the fundamental biology is understood.”

Even now, Fishman said, “We do clearly believe that we have a shot at making the medicines, but it’s very early, and I think that to pretend that we see a linear track here would be overstating the case.”

In recent years, researchers have begun to unravel much about the mechanism of Huntington’s: It appears that in patients with the disease, cells produce an abnormal protein that breaks into smaller, toxic pieces, which then clog up the cells.

“If, every time you took out the garbage you left a Kleenex behind, soon your room would be filled with Kleenex,” said Dr. Anne Young, who is chief of neurology at Mass. General and the driving force behind much of the hospital’s concentration on Huntington’s.

The toxic fragments seem to impair the mitochondria, the energy factories of cells, and also go into the nucleus of the cell and cause the wrong genes to be put into action.

But major mysteries remain; scientists still do not even know the normal function of Huntingtin, the mutant protein.

As they sort out possible remedies, the researchers face a major problem: Huntington’s causes degeneration at a glacial speed, which is good for patients but bad for researchers in a hurry to find a cure.

“If you have a rust inhibitor that stops rust right away, and you put it on your rusty car, and say, ‘Did the rust stop?’ You won’t know” for some time, because rusting is such a slow process, said Mass. General researcher Dr. Jang-Ho Cha.

Unwilling to wait years to see if potential treatments work, researchers are urgently trying to develop “biomarkers” of Huntington’s disease — telltale biological signs that the disease has progressed, or been stopped in its tracks. Some are signals of disease activity that show up in the blood of Huntington’s patients; others are brain imaging techniques that promise to pick up deterioration quickly.

For now, the treatments farthest along in humans are anything but high-tech: They are powders called Creatine and Co-enzyme Q-10 that are available in any health food store and seem able to help patients feel better, longer.

But almost every month brings more reports in top scientific journals of significant new findings on the root causes of the disease.

“For the first time, we’re no longer in the dark — it’s filled with light, we know what we have to do,” said Michael Hayden of the University of British Columbia, a leading Huntington’s researcher.

But for all the enthusiasm of researchers like Hayden, Bliss is reserving judgment on his own fate. Bliss, whose constructive attitude won him an award last year from the New England branch of the Huntington’s Disease Society of America puts his faith in his own ability to cope, whatever the future brings.

If a cure is found, “I’ll be the happiest one in the world and the first one in line, but I’m not going to wait for something like that to happen,” Bliss said. “A lot of people just wait for things to make them happy.”