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Sanfilippo Syndrome Might Be Treatable with Alzheimer Drugs

Scientists at UCLA have obtained evidence that a form of the rare genetic disease known as Sanfilippo syndrome may be treatable with new Alzheimer’s disease drugs directed against the P-tau protein. Four different enzyme deficiencies cause Sanfilippo syndrome, leading to the disorder's classification as type A, B, C, or D. The UCLA team studied type B, the second most common form, which causes severe mental retardation, dementia, and death as early as age 14. "We knew that Sanfilippo syndrome type B results from a mutation of the gene that produces the enzyme needed to break down sugar molecule chains [mucopolysaccharides] in the body," said Dr. Elizabeth Neufeld, of the David Geffen School of Medicine at UCLA, and senior author of the study. "We studied the disease in mice bred to possess the same gene defect seen in human patients." Neufeld's team found that mice with the defective gene produce higher amounts of two proteins called lysozyme and P-tau. They tracked the proteins to neurons in the medial entorhinal cortex, an important memory center in the brain. This is one of the first areas to be affected by Alzheimer's disease, and the region also has been implicated in abnormalities in Sanfilippo syndrome. Earlier research had linked high levels of lysozyme to the production of P-tau, a misshapen protein that helps form the strands that clump into tangles in the brain. These tangles impair neuron function and are a hallmark of Alzheimer's and other degenerative brain diseases. "This is really exciting," said Dr. Stanislav Karsten, also an author of the study. "If we can replicate our discovery of P-tau in the brains of human patients, it may be possible to treat Sanfilippo syndrome with new drugs created for Alzheimer's disease. We believe our finding will accelerate the development of an effective therapy for this heartbreaking disorder." This work was reported in the May 5 early online edition of PNAS. [UCLA release] [PNAS article]