Saturday, January 31, 2009

i got this email from my buddy eddie

The path to a cure; ALS specialist Dr. Robert H. Brown Jr. joins elite team at UMass.
Byline: Elizabeth Cooney When Dr. Robert H. Brown Jr. says it, it sounds so simple. "These diseases will yield," he said. "We just can't take no for an answer." The new head of neurology at University of Massachusetts Medical School UMMS is ranked fourth in primary care education among the nation’s 125 medical schools in the 2006 U.S.News & World Report annual guide, “America’s Best Graduate Schools”. UMMS is also a major center for research. and UMass Memorial Medical Center is single-minded in his determination to find better treatments for such devastatingdev·as·tate tr.v. dev·as·tat·ed, dev·as·tat·ing, dev·as·tates1. To lay waste; destroy.2. To overwhelm; confound; stun: was devastated by the rude remark. ..... Click the link for more information. neuromuscular diseases as amyotrophic lateral sclerosis amyotrophic lateral sclerosis (ALS) (ā'mīətrōf`ik, sklĭrō`sĭs) or motor neuron disease, , better known as Lou Gehrig's disease Lou Geh·rig's diseasen.See amyotrophic lateral sclerosis. . In October he left Massachusetts General HospitalMassachusetts General Hospital Health care The major teaching hospital for Harvard Medical School, widely regarded as one of the best health care centers in the world ..... Click the link for more information. and Harvard Medical SchoolHarvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. ..... Click the link for more information. to find a faster pathway to treatments at the state's medical school The lure was RNA interferenceRNA interferencen.A process in which the introduction of double-stranded RNA into a cell inhibits the expression of genes. ..... Click the link for more information., or RNAi for short, the mechanism that can silence genes. UMass professor and Nobel laureate Craig C. Mello was one of two scientists to discover the biological process in 1998. Since then, the medical school has added to its cadre of RNAi researchers by recruiting distinguished scientists such as Dr. Brown, who was already collaborating with UMass experts. The school's proposed Advanced Therapeutics Cluster will include a center devoted to RNAi, part of the state's $1 billion life sciences initiative. RNAi holds promise for treating diseases by shutting off defective genes that make harmful proteins. In ALSAls (äls), Ger. Alsen, island, 121 sq mi (313 sq km), Sønderjylland co., S Denmark, in the Lille Bælt, separated from the mainland by the narrow Alensund. ..... Click the link for more information., mutant genes produce proteins that kill nerve cells needed to move muscles. Most people die within three to four years after first developing muscle weakness and then paralysis. "I spent 30 years at the Mass. General Hospital, which is a wonderful institution," Dr. Brown, 61, said last month in his UMass Medical School office, already adorned by images of Lou Gehrig and photos of Red Sox players at ALS fundraisers. "But it seemed to me that I would probably make more progress here by joining forces with the people who made the basic discoveries in this (RNAi) technology. I just thought the route would be more direct here." Dr. Brown, both a research scientists and a neurologist who sees patients, began studying ALS in 1979. It was through his clinical work that he began to investigate the genetic underpinnings of ALS. One of his patients, Oscar Horvitz, was the father of H. Robert Horvitz H. Robert Horvitz (born May 8, 1947) is an American biologist best known for his research on the nematode worm Caenorhabditis elegans. He is currently at the Massachusetts Institute of Technology where he is Professor of Biology and a member of the McGovern Institute for , a scientist at MIT MIT - Massachusetts Institute of Technology who later won a Nobel Prize Nobel Prize, award given for outstanding achievement in physics, chemistry, physiology or medicine, peace, or literature. The awards were established by the will of Alfred Nobel, who left a fund to provide annual prizes in the five areas listed above. for his work on the genetic regulation of organ development and programmed cell death pro·grammed cell deathn.See apoptosis.
programmed cell deathproposed system of cell death, often including poly(ADP)-ribosylation, ensures that a cell will not survive if it is so badly damaged that its recovery would harm the . After Dr. Brown had the sad task of confirming a diagnosis of ALS in his patient, he began discussing research with his patient's son. At the time, the technology to find genes and map them was just entering laboratories, where scientists were trying to divine what they did. "Bob and I started talking about this horrific disease, and what we might do about it," Dr. Horvitz said in an e-mail interview about Dr. Brown. "At that point we embarked upon collaborative studies.... We agreed that the emerging technologies of human genetics Human geneticsA discipline concerned with genetically determined resemblances and differences among human beings. Technological advances in the visualization of human chromosomes have shown that abnormalities of chromosome number or structure are surprisingly offered new approaches, and it was this work that led to the identification of the first ALS gene, known as SOD1. Since then Bob has continued to pioneer the application of ever-more sophisticated genetic methods to ALS research." SOD1 was identified in 1993, breaking open the world of ALS research. The gene produces superoxide dismutase, an enzyme that protects cells from damage wrought by toxic free-radical molecules. Defective forms of the gene were found in families who had ALS. Most cases of ALS are sporadic, meaning they strike people who have no family history of the disorder, but finding the gene implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.2. in the inherited forms offers a keyhole through which to learn about all forms of the disease. The scientific paper reporting the breakthrough was dedicated to Oscar Horvitz. Once the gene was identified, the next step was to study it in specially bred laboratory mice and then devise ways to fix it. "It's been a long slog. It became painfully clear that the treatments would be very difficult to find. This was a very hard nut to crack, and there were no easy fixes," Dr. Brown said. "Because of the frustration of working for 10 years with conventional therapies without success, it seemed to me we needed to look for something new and to go as far upstream as one could to shut off the disease process right at the start." That's when Dr. Brown and his colleagues began to get very interested in gene silencing through RNAi. "There are several lines of study suggesting that the technology actually works in mice," he said. "The question is how best to get it in people." One way would be to inject active RNAi molecules into the spinal fluid of patients that would then thwart the mutant gene, but there are doubts about how effective that would be, he said. Another approach is more complicated: using gene therapy to deliver into the spinal cord a gene that uses the machinery of the cell to continuously make gene-silencing RNA RNA: see nucleic acid.
RNA in full ribonucleic acidOne of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic . Both methods pose challenges. Of the two, Dr. Brown thinks the gene therapy-RNAi combination holds the most promise for achieving a sustained effect. It's no coincidence that the planned UMass therapeutics cluster includes a gene therapy center as well as an RNAi center. (The third is devoted to stem cell science.) "The new dean is a gene therapist, so suddenly it's like a perfect storm," Dr. Brown said. "This isn't just a laboratory exercise. He's extremely serious about seeing this happen and implementing programs. That feeds in perfectly to the idea of a more effective way to deliver RNAi therapy." Dr. Brown's sense of urgency comes from the patients he hopes to help. They don't have a lot of time. "Bob is somebody who is a very caring and compassionate physician," said Dr. Terence R. Flotte, dean of the medical school since April 2007. "His motivation is heavily centered around coming up with solutions for the patients who are so tragically affected. People say stuff like that a lot, but you can see in his eyes - that's what really matters to him." Dr. Brown's optimism about finding a cure was clear last month, two days after the presidential election. "What did someone say the night before last?" he asked. "`Yes, we can.'" CUTLINE

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