Florida - November 2012 Archives

JACKSONVILLE, Fla. — A novel test that measures proteins from nerve damage that are deposited in blood and spinal fluid reveals the rate of progression of amyotrophic lateral sclerosis (ALS) in patients, according to researchers from Mayo Clinic's campus in Florida, Emory University and the University of Florida. Their study, which appears online in the Journal of Neurology, Neurosurgery & Psychiatry, suggests this test, if perfected, could help physicians and researchers identify those patients at most risk for rapid progression. These patients could then be offered new therapies now being developed or tested. ALS — also known as Lou Gehrig's disease — is a progressive neurodegenerative disease caused by deterioration of motor neurons (nerve cells) that control voluntary muscle movement. The rate of progression varies widely among patients, and survival from the date of diagnosis can be months to 10 years or more, says Kevin Boylan, M.D., medical director of the ALS Clinic at Mayo Clinic in Florida. "In the care of our ALS patients there is a need for more reliable ways to determine how fast the disease is progressing," says Dr. Boylan, who is the study's lead investigator. "Many ALS researchers have been trying to develop a molecular biomarker test for nerve damage like this, and we are encouraged that this test shows such promise. Because blood samples are more readily collected than spinal fluid, we are especially interested in further evaluating this test in peripheral blood in comparison to spinal fluid." There are no curative or even significantly beneficial therapies in clinics now for ALS treatment, but many are in development, Dr. Boylan says. A test like this could help identify those patients who are at risk for faster progression of weakness. With experimental treatments that primarily slow progression of ALS, detecting a treatment response in patients with faster progression may be easier to detect, says Dr. Boylan. Now, patients with varying rates of progression participate together in clinical studies, which can make analysis of a drug's benefit difficult, he says. "If there were a way to identify people who are likely to have relatively faster progression, it should be possible to conduct therapeutic trials with smaller numbers of patients in less time than is required presently," Dr. Boylan says. A longer-range goal is to develop tests of this kind to gauge how well a patient is responding to experimental therapies, he adds. The test measures neurofilament heavy form in blood and spinal fluid. These are proteins that provide structure to motor neurons, and when these nerves are damaged by the disease, the proteins break down and float free in blood serum and in the spinal fluid. Earlier research in this area was conducted by Gerry Shaw, Ph.D., a neuroscientist at the University of Florida, who is the study's senior investigator and the developer of the neurofilament assay used in the study.

JACKSONVILLE, Fla. — A gene so powerful it nearly triples the risk of Alzheimer's disease has been discovered by an international team including researchers from Mayo Clinic. It is the most potent genetic risk factor for Alzheimer's identified in the past 20 years. The findings were reported Wednesday in the online edition of the New England Journal of Medicine. The team included researchers from 44 institutions around the world, including 10 from Mayo Clinic's campuses in Florida and Minnesota. The study was led by John Hardy, Ph.D., a researcher at the Institute of Neurology at University College London and a former professor at Mayo Clinic in Florida. The researchers used new sequencing techniques to home in on the TREM2 gene. Additional TREM2 sequencing was then performed, in part, by scientist Aleksandra Wojtas in the Mayo Clinic in Florida laboratory of Rosa Rademakers, Ph.D. These studies led to identification of a set of rare variants in TREM2 that occurred more often in 1,092 Alzheimer's disease patients than in a control group of 1,107 healthy people. The most common variant, R47H, was then evaluated in follow-up studies of a large number of Alzheimer's disease patients and controls. Minerva Carrasquillo, Ph.D., a scientist in the Mayo Clinic in Florida laboratory of Steven Younkin, M.D., Ph.D., spearheaded the direct genotyping and analysis of R47H in DNA samples from 1,994 Alzheimer's disease patients and 4,062 "control" participants — individuals verified not to have Alzheimer's. The patients and control participants were evaluated by Mayo Clinic physicians, led by co-authors Dennis Dickson, M.D., Neill Graff-Radford, M.D., and Ronald Petersen, M.D., Ph.D. These follow-up studies showed unequivocally that the R47H variant of TREM2 substantially increases the risk of Alzheimer's disease. "The TREM2 variant may be rare, but it is potent," Dr. Carrasquillo says. "In our series, it was present in 1.9 percent of the Alzheimer's patients and in only 0.37 percent of the controls. This strong effect rivals that of the well-established genetic variant known as APOE 4, and it was observed both in our study and in the independent study led by deCODE that was published with ours. R47H isn't fully penetrant — meaning that not all people who have the variant will develop Alzheimer's and in those who do, other genes and environmental factors will also play a role — but like APOE 4 it does substantially increase risk." Dr. Younkin comments: "R47H is the first goldilocks variant to show strong association with Alzheimer's disease." Now being identified using the new sequencing technologies, goldilocks variants are an important type of rare variant so named because they are just right, not too rare and strong enough to show highly significant association in well-powered follow-up genotypic studies like the one performed at Mayo. "There is a broad consensus that prevention will be the best way to manage Alzheimer's disease," Dr. Younkin says. "In my view, common variants like APOE 4 and goldilocks variants like TREM2 R47H are important because they could be used, in principal, to identify many healthy people at high risk of Alzheimer's disease who would be suitable for prevention trials. Patients whose Alzheimer's disease is driven by high risk genetic variants will frequently transmit these variants to their children. We now know that it takes a long time for the pathology of Alzheimer's disease to produce symptoms, so prevention in children who receive these variants would ideally begin when their elderly parents are diagnosed."