updated 11-Jan-02
Dr. Pamela L. Larsen and Dr. Catherine F. Clarke of the University of California, Los Angeles, have made an amazing discovery. Judged by the potential of their discovery to relieve human suffering they may be our next Nobel Laureates. Their work may have immediate application for the treatment of Huntington's Disease.
In the light of this day, this new discovery develops a fascinating story of the resolution of wrong turns and missed opportunities for HD research. HD is tough condition to understand. The mechanisms of the HD defining gene are still being debated. The structure of the gene is known in detail. The terrible devastation of untreated HD is known in all aspects. It is not known how gene ravages patients. There is no step by step recorded animation of the events caused by the gene. One by one, theories about HD have fallen. In a striking manner HD has no regard for ideas of how things should work. Today the glory of HD researchers is that they can do large expensive clinical trials that fail to ease suffering.
Eventually the puzzle will be solved. But for now more effective and universal treatment of HD patients are the immediate problems to be solved by research. New promising treatments need attention. Treatments like creatine, EPA and exercise need to reach all HD patients.
It has been known for many years that restricting calories in normal, so called wild, mice extended their lives. The popular theory is that restricting calories reduces oxidative cellular stress and prolongs vitality and life. Trials, still in progress, for primates on restricted calorie diets indicate that restricted calorie diets will extend human lives.
It has been known and ignored that restricting calories for HD mice greatly improves their condition. Normally rats fed a toxin to decrease cell energy develop defects that mimic HD. These rats are an accepted model for the expanded gene defects. Treatments for these rats have similar results for the HD genetic mice.
Early in 1999 researchers at the University of Kentucky restricted the diet of toxin mice models and concluded. " The toxin caused severe motor problems in the normally fed rats, but had essentially no effect on the rats that had been on the reduced calorie diet."(ref) . This was fertile ground for HD research. There was no follow up on this solid irrefutable discovery. For three years no HD researcher thought the following question was relevant: What substance, if any, that was restricted by diet provided this amazing protection? The only answer was, "That is not where the money is."
The award winning researchers Larsen and Clarke asked a different but related question. What decreased substance, if any, in diet was causing worms on a restricted diet to live longer?
They developed theories about what substances in food could be singularly restricted in an otherwise normal diet for benefit. The lab animal was a small worm with the pretty name of c. elegans. They found that coenzyme Q restricted diets greatly prolonged the life of c. elegans.
It was a stroke of incredible insight that the researchers even suspected coenzyme Q. The most popular member of the coenzyme Q group is coenzyme Q10. Q10 is a darling of manufacture supported research. Q10 is touted as beneficial for almost all diseases. In contrast the researchers found, "These data indicate that a dietary source of coenzyme Q has a profound life shortening effect on the wild-type animals." (ref) The comparison is made between animals on a normal diet and a Q-less diet.
Two curious events were taking place last year. CARE-HD researchers were hoping to prove that very large amounts of dietary coenzyme Q, (Q10), would treat HD. Meanwhile researchers at UCLA were discovering that restricting dietary Q would protect cells and extend animal life. The rationale for the CARE-HD trials was shown to be completely wrong by the UCLA researchers. The HD researchers had not done their homework before launching an expensive and fruitless trial.
Fortunately for the patients in the CARE-HD trials, Q10 is tightly regulated and brain levels of Q10 do not rise, even with massive supplementation. There is some evidence that restricting Q10 by a Q-less diet will decrease brain levels of Q10. The Q-less diet has a compelling probability for the successful treatment of HD. This is because at some point in the aging process coenzyme Q probably becomes an effective pro-oxidant.
At the conclusion of the failed CARE-HD trials contacted researchers thought that statins would not treat HD because they lower coenzyme Q. There were only two patients on statins, too small a sample for any conclusions. Besides the patients on statins may of been taking Q10 and the statins were not randomly assigned.
Today, in the light of Larsen and Clarke we know the HD researchers were wrong. It is clear that statins and Q-less diets present a great opportunity for HD research that will really help patients. --Jerry 05-Jan-02
Thought you might find these Woody quotes relevant.
"Life has got a habit of not standing hitched. You got to ride it like you find it. You got change with it. If a day goes by that don't change some of your notions for new ones, that is just about like trying to milk a dead cow." (1)
"I see a better world a-comin', yes, I know and I know
I see a better world a-comin', yes, I know.
Out of storms and winds and rains,
Out of sorrow, out of pain,
I see a better world a-comin', that I know."
Both quotes are included in "Woody Guthrie and Me" by Ed Robbin. (1) is taken from "Woody Sez." (2) is from "Woody Guthrie Folk Songs."
Keep on keepin' on,
New York, NY, December 21, 2001 – Over the past few years, Huntington’s Disease (HD) has gone from being a virtually unknown disorder to one that is now recognized by the federal government as a “model” for other neurodegenerative diseases. In May, the Huntington’s Disease Society of America (HDSA) formed a groundbreaking partnership in the neurodegenerative field through a joint sponsorship between government and a voluntary health agency. The incredible growth and accomplishments in the field of HD research have been recognized by Discover magazine (January 2002 issue) as one of the top 100 scientific advances in 2001.
Over the past year alone, several investigators from the Huntington’s Disease Society of America’s Coalition for the Cure, an elite group of HDSA-funded scientists, have made significant advancements in HD research. In March, Christopher Ross, M.D., Ph.D. and his team at John’s Hopkins University discovered how the HD gene attacks and kills cells. The details of this significant achievement were published in the March 23rd edition of the journal, Science. Also published in Science this year was research by Elena Cattaneo, Ph.D. Her research discovered the role that normal huntingtin protein plays in the brain. Most recently, Leslie Thompson, Ph.D. and her team at the University of California, Irvine made significant headway in halting and preventing the neurodegeneration that is characteristic in Huntington’s Disease. This research discovery was published in the October 18th edition of Nature.
Since 1996, HDSA’s commitment to research funding has grown from $183,000 to $4 million in the coming year, with a goal to raise $25 million for new research initiatives over the next five years. “The momentum in HD research continues to accelerate and we are very hopeful that effective therapies, and ultimately a cure, for Huntington’s Disease are well within our reach,” says Barbara Boyle, National Executive Director/CEO, HDSA. The answers we find for HD today may lead to therapies, and ultimately a cure, for Parkinson’s, ALS (Lou Gehrig’s disease), Alzheimer’s and other related diseases.
Huntington’s Disease is an inherited, degenerative brain disorder that results in the progressive loss of control of both the mind and the body. Each child of an affected parent has a 50% chance of inheriting the disease. Presently, there is no effective treatment or cure for this deadly illness that affects 30,000 Americans and places another 200,000 at-risk.
The Huntington’s Disease Society of America is a national non-profit voluntary health agency that is dedicated to finding a cure for HD, by funding both basic and clinical research, while providing vital services to those affected by this life-altering disease. For more information about HD and HDSA please visit the national web site at www.hdsa.org or call (800) 345-HDSA. To read the Discover magazine article about HD, please visit www.discover.com.