Gentilmente potreste commentare questo articolo? (da: <http://www.cureangelman.org/news/LongShot.html> http://www.cureangelman.org/news/LongShot.html) Grazie mille Saluti AM A "Long Shot" Pays Off Grandmother's Alzheimer's leads scientist to a major breakthrough in Angelman Syndrome By Elizabeth McBreen As a research scientist, Edwin Weeber, Ph.D. <http://www.cureangelman.org/sab.html#ew> , never thought he would be in a position to receive fan mail. Weeber, who is currently an Associate Professor at the University of Southern Florida (USF), has spent his graduate and post-graduate career conducting research on Angelman syndrome (AS). After 10 years of research and testing, he has discovered how to reverse the deficits of the disorder in mice. Angelman syndrome, first discovered in 1965 by an English doctor, Harry Angelman, is a disorder that causes severe developmental delays, impedes speech and motor coordination. Other symptoms such as seizures and microcephaly affect about 80 percent of patients, according to the Angelman Syndrome Foundation Web site (www.angelman.org). Not evident at birth, AS is generally diagnosed after the age of 3 years. Relatively rare, AS affects between 1 in 15,000 and 1 in 30,000 people, and it is common for patients to exhibit some of the same earmarks as autism. These can include hand flapping and a short attention span. Although the two disorders can present similar symptoms, Weeber says that AS is considered more severe in nature. Weeber started out as a graduate student studying microbiology at Baylor College of Medicine in Texas. Because his grandmother was suffering from Alzheimer's at the time, he was drawn to research of the brain, specifically learning and cognitive ability. Weeber began working with David Sweatt, Ph.D., who was conducting cognitive studies in his lab. While working in Sweatt's lab, Weeber became particularly interested in the hippocampus, a part of the brain that plays a role in memory. Down the hall from Sweatt's lab, another researcher was studying AS in mice models. "Angelman syndrome is a maternal imprinted disorder and there are no expressions of it in some parts of the brain - one of these is the hippocampus. So instead of studying random things in the hippocampus, I decided to study Angelman syndrome," says Weeber. Prior to Weeber's studies, most of the research that had been conducted on AS had been genetic. The gene that carries the disorder was identified in 1997. Abnormal function in this gene, UBE3A, had been targeted as a possible cause for the disorder. UBE3A is a gene that is imprinted on the brain, meaning that the body knows what part of the gene is maternal and what part is paternal. "We get half of all of our genes from our mother and half from our father. The deletion or mutation of the mother's gene causes AS," says Weeber. Interested in the biomedical aspects of the disorder, he began studying enzymes and proteins in the brain that work with this gene. Weeber would make his groundbreaking discovery while working in his own lab at Vanderbilt University. As he worked with his mice models from Baylor, Weeber discovered that he could reverse the effects of AS by regulating a particular enzyme, CaMKII. CaMKII is "an enzyme that is essential for learning and memory, as well as normal motor learning. We found that one of the biological abnormalities in AS mice was reduced CaMKII activity. It was known that reduced CaMKII activity results in neurological deficits. Thus, we concluded that regulating CaMKII in the mice may reverse their neurological deficits," says Weeber. When Weeber tested his theory by crossing mice with AS and mice with a mutation that caused them to retain their CaMKII activity, the resulting offspring had no AS symptoms. The seizure activity, mental retardation and problems with motor coordination all disappeared in the mice models. These results caused Weeber to conclude that the deletion or mutation of the maternal part of the UBE3A gene caused reduced CaMKII activity, resulting in AS. Weeber says that when the activity of CaMKII enzyme is regulated, the deletion of the maternal part of the UBE3A gene is corrected. He adds that this enzyme is not produced until after the mice are born. This may also be the case in humans. Weeber says that this conclusion is an important when it comes to the treatment of AS. "This suggests that AS is not developmental in nature, but rather biochemcial. In other words, the brain appears to be wired correctly, but the change in CaMKII activity prevents the proper communication between the neurons in the areas of the brain where maternal UBE3A imprinting occurs." Six months ago, Weeber, his wife and their son moved to Florida. The couple has since welcomed a new daughter to the family, and Weeber has taken the position as Associate Professor at USF. Weeber and his wife, who has a Ph.D. in neuroscience, feel that a move to USF is a natural progression because the school is known for its work in cognitive studies. At USF, Weeber will pursue therapeutic approaches for AS patients. The results found in Weeber's mice models were obtained through genetic engineering, and so this method is not applicable to humans. He says that one of the approaches for treating AS in humans could be a pharmacological one that would modulate CaMKII. Another possibility is adeno-associated virus (AAV). Weeber explains that this is a method for introducing foreign genes in neurons of the central nervous system. AAV can be used to either introduce CaMKII with the same mutation that was used to rescue the AS mice, or introduce a UBE3A gene that would take the place of the deleted or mutated maternal UBE3A gene. Weeber plans to begin researching the use of AAV to treat AS in the next six months. While Weeber's discovery has many positive implications for AS patients, it could also be good news for people with autism. He says that while AS patients and autistic people look very different, there are genetic similarities. "Future research may in fact find a relationship between changes in UBE3A and autism," says Weeber. Other disorders having to do with cognitive function may also benefit from his research. For now, parents of AS children are celebrating Weeber's work. Terry Jo Bichell is a Visiting Scholar at Vanderbilt Kennedy Center for Research on Human Development and the mother of a nine-year-old boy with AS. Bichell took a position at Vanderbilt not long after Weeber's article was published. "I suddenly realized that concentrating on a cure for AS was not a pie-in-the sky day dream, but a real possibility," says Bichell. "Now it feels like the answer lies just beyond a flimsy curtain. It is almost in sight." For more of this article please subscribe to Spectrum <http://spectrumpublications.com/> today. --- Questa e-mail è priva di virus e malware perché è attiva la protezione avast! Antivirus. http://www.avast.com