Weizmann scientists move to defuse Huntington's time bomb

The new disease model appears to fit all the facts and to provide a good explanation for the onset and progression of all the known trinucleotide repeat diseases.

By JUDY SIEGEL-ITZKOVICH
microscope 88 (photo credit: )
microscope 88
(photo credit: )
Huntington's disease is a genetic time bomb: This horrific disorder appears at a predictable age in adulthood, causing a progressive decline in mental and neurological function, and finally death. So far, there is no cure for Huntington's or a number of similar ailments collectively known as trinucleotide repeat diseases. They are caused by an unusual genetic mutation: A three-letter piece of genetic code is repeated over and over in one gene. Scientists at the Weizmann Institute in Rehovot have now proposed a mechanism that provides an explanation for the remarkable precision of the time bomb. This explanation may point researchers in the direction of a possible prevention or cure. The number of repeats in Huntington's patients ranges between 40 to over 70. Scientists have noted that, like clockwork, one can predict - by how many times the sequence repeats in a patient's gene - both the age at which the disease will appear and how quickly it will progress. The basic assumption has been that the protein fragment containing the amino acid (glutamine) encoded in the repeating triplet slowly builds up in the cells until it reaches toxic levels. This theory, unfortunately, fails to explain some of the clinical data. For instance, it doesn't explain why patients with two copies of the Huntington's gene don't exhibit symptoms earlier than those with a single copy. Plus, glutamine is produced in only some trinucleotide diseases, whereas the correlation between sequence length and onset age follows the same general curve in all of them, implying a common mechanism not tied to glutamine. Research student Shai Kaplan in Prof. Ehud Shapiro's lab in the institute's biological chemistry department and the computer sciences and applied mathematics department realized the answer might lie in somatic mutations - changes in the number of DNA repeats that build up in our cells. The longer the sequence, the greater the chance of additional mutation, and the scientists realized that the genes carrying the disease code might be accumulating more and more DNA repeats, until some critical threshold is crossed. Based on the literature on some 20 known trinucleotide repeat diseases and their knowledge of the mechanisms governing somatic mutation, Shapiro, Kaplan (also in the molecular cell biology department), and Dr. Shalev Itzkovitz created a computer simulation that could take a given number of genetic repeats and show both the age of onset and the way in which the disease would progress. Their findings were recently presented in PLoS Computational Biology. The new disease model appears to fit all the facts and to provide a good explanation for the onset and progression of all the known trinucleotide repeat diseases. Lab experiments could test this model, say the scientists and, as it predicts that all these diseases operate by somatic expansion of a trinucleotide repeat, it also suggests that a cure for all might be found in a drug or treatment that slows the expansion process. PREPARING FOR THE 'BIG ONE' Israelis who were shaken up by two recent earthquakes can take a Magen David Adom course in preparing for such a natural disaster. MDA said the four-hour course, which trains participants to help themselves, their family members and neighbors in the event of an earthquake, costs NIS 50 per participant. Everyone by now knows that Israel is overdue for a "Big One" of 7.0 or more on the Richter Scale, when it comes, an estimated 16,000 may be killed and 90,000 injured, among them 6,000 seriously. MDA staffers will teach how to act during and after a powerful earthquake, basic fire safety rules and how to rescue the injured. A severe quake would damage road, electrical cables, telephone wires and water pipes. Rescue forces will have difficulty getting to all affected areas, and problems reaching every home. Thus MDA's first aid course can save lives and boost survival during the first few hours, says MDA director-general Eli Bin. Registration for the course around the country is by calling 1-700-500-430 or by going to www.mdais.org. IN MK'S MEMORY Ten months after the death of Yisrael Beitenu Knesset member Yuri Shtern from brain cancer, a Center for Holistic Help to cancer patients and their families has been established in his memory at Jerusalem's Shaare Zedek Medical Center. The facility was initiated by the Yuri Shtern Foundation (www.yurishtern.org.il), his wife Lena and son Marek. Complementary medical care is being offered to improve patients' physical and psychological conditions, help them cope with cancer and improve their chances of recovery. Dozens of volunteers who have studied complementary medicine are giving treatments at no cost. Shtern, whose battle against cancer included both conventional and complementary care, tried to pass laws that would regulate complementary medicine practitioners, but so far the bills have not become law. CHILD-FRIENDLY UNIFORMS Rivka Sofer, chief nurse in the pediatrics department of Safed's Ziv Hospital, saw that medical personnel in children's wards abroad wear uniforms with colorful cartoon characters to reduce fear in young patients. She was so persuaded that such tops, with animal designs, were adopted at Ziv's pediatric ward for nurses as well as patients' pyjamas. "The first contact between nurses and patients revolves around the characters on the blouses; the children are amused, less fearful and able to undergo treatment when they are more relaxed," she explains.