We will keep watch over the researchers and learn from them. First of all to have the best possible life with HD. Second of all to be in the best possible condition to benefit the most from a cure. We worry about those that are not continually developing their own Triads to fight the Triad of HD. -- Jerry

Posted to HDLighthouse: 08Aug02 HDL Update: Unusual Collaboration Yields Leap In Disease Fight

HD Researchers Work Together "Huntington's is a devastating disease, and the work is extremely hard,'' said Nancy Wexler, president of the Hereditary Disease Foundation, which provided the lion's share of funding for the collaboration. ''By working together, we've gained a huge leap. I think it's the beginning of something extremely valuable and fruitful."

Dr. Jim Olson never envisioned the scientific journey upon which he was about to embark when he boarded a plane to Boston more than three years ago to attend the wake of his academic mentor.

Olson had studied under Dr. Jack Penney and Penney's wife, Dr. Anne Young, both noted Huntington's disease researchers, in the early 1980s. But Olson's career had led him in a different direction, unraveling the mysterious assault that cancer mounts on children's brains.

When Penney died, Olson was among a coterie of scientists who gathered around Young. And out of tragedy came a collaboration involving academia, industry, and the nonprofit sector that would lead to the creation of a large public database and a series of discoveries critical to the future of Huntington's research. It was their tribute to Penney.

Detailed in six papers in this month's issue of the journal Human Molecular Genetics, the group's findings advance hope for discovering therapies to slow or reverse the steady degeneration of the brain and body caused by Huntington's disease. Researchers say the findings, and the database of genetic information, lay groundwork for better understanding the disease and preventing it.

Researchers first discovered a genetic marker for Huntington's disease in 1983. The identification of the Huntington's gene followed in 1993, paving the way for much additional research. But finding a treatment to slow or stop the disease has proved elusive. The Huntington's gene sets into motion a series of complex biological interactions, many of which remain little understood.

The goal of the collaboration was to analyze and compare the genes active in healthy mice with those active in strains of mice modeled to mimic Huntington's disease. If a distinct genetic pattern emerged among the sick mice, it could yield clues into the cascade of biological events triggered by the disease. Huntington's attacks the brain, gradually robbing a person of the ability to walk, talk, and think. Nationwide, 30,000 people have the disease; an additional 200,000 are at risk of inheriting it.

''Right now, we can do a lot to manage the physical, behavioral, and emotional symptoms, but the disease keeps going,'' said Dr. Steven Hersch, an associate professor at Massachusetts General Hospital and Harvard Medical School. ''We aren't slowing down the disease or keeping people from dying.''

The collaborative effort began shortly after Penney's death in January 1999. At the wake, Olson began talking to another researcher, Ruth Luthi-Carter, who had been working with Penney and Young. He suggested she use a new technology, known as DNA microarrays, or gene chips, that would allow her to measure the expression of thousands of genes in a single experiment to study the genetic pattern Huntington's disease created in mice.

Olson, who had worked with the chips in his research at the Fred Hutchinson Cancer Research Center in Seattle, agreed to help her. The results were thrilling. But to be meaningful, they needed to be confirmed in other lines of mice that had been altered to develop Huntington's disease. And for that, they needed the cooperation of scientists and laboratories that had developed other mouse models of Huntington's disease.

Within several months, the collaboration grew to include more than 50 researchers from 19 academic institutions, the nonprofit Hereditary Disease Foundation, Cambridge-based 3rd Millennium Inc., and California-based Affymetrix Inc. The Hereditary Disease Foundation provided millions in funding. Affymetrix supplied the gene chips. And 3rd Millennium, using a portion of a $1.8 million federal grant, developed software to allow the researchers to manage and interpret the enormous amount of data generated by the experiments. That database was made public yesterday.

Over two years, the scientists studied which genes were active and which were inactive in eight different types of mice with Huntington's disease. They compared the gene-expression patterns among the sick mice to those of the healthy mice. And the experiments were conducted with as much uniformity as possible so results could be compared across the board.

''We felt very lucky to be able to collaborate with so many different laboratories, many of which had spent a lot of effort to develop these disease models,'' said Luthi-Carter, an instructor at Massachusetts General and Harvard Medical School. ''It wasn't a given. In some areas of science, competition and ego are very much at play.''

Together, the scientists identified the group of genes first altered by the disease, a discovery that could lead to therapies that intervene at the very earliest stages of Huntington's before symptoms appear. They discovered that genetic changes in muscle mirror those in the brains of Huntington's patients, which could lead to the ability to monitor the progression of disease in patients and their response to therapy without brain scans or biopsies.

They found that many genetic changes caused by Huntington's also occur in models of other degenerative brain disorders, suggesting those biological processes may be key to the progression of Huntington's and, therefore, potentially important points at which to intervene in the disease. They learned that the protein produced by the Huntington's gene causes many more genetic changes as it breaks down, supporting research on therapies aimed at keeping the protein intact.

''We accomplished in two years what would have taken more than a decade if we had tried to sort it out independently,'' Olson said.

Olson said he and his colleagues are already pursuing additional research based on these findings, even testing potential drugs in laboratory and animal experiments in hopes of advancing therapies into human clinical testing within five years. The scientists said the genetic insights they've gained will help guide future research as they work to understand all of the biological events triggered by Huntington's and sort out which are most critical to the progression of the disease.

Just the existence of the public database promises to advance the pace of science, said Wexler. Huntington's researchers all over the world can query the database to answer important questions without repeating work that has already been done. Insights they glean from the genetic data could further focus their own research, send them in new directions, or open up whole new avenues of investigation.

''It's going to be like an ongoing explication of a text,'' Wexler said. ''This is really the first chapter. There's a lot to be followed up on.''

Source:Adapted from the story that ran on page C1 of the Boston Globe on 07Aug02 by Naomi Aoki, Globe Staff, © Copyright 2002 Globe Newspaper Company.
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