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Cancer researchers add spice to research against rare neuromuscular disease

e than 70 co-factors are known, offering many new targets to potentially stop conditions like Kennedy's disease that involve the receptor itself.

Chang's work has led to an understanding of the genetic basis of Kennedy's disease, which affects the motor neurons that go from the spine to certain muscles, causing muscle weakness and wasting throughout body. Symptoms typically include difficulty speaking and swallowing, and weakness in the arms and legs. Patients are often diagnosed in their 30s and 40s, and while most live a normal life span, many patients end up using a wheelchair and have serious health difficulties. Currently there is no way to slow the progression or prevent the disease, which is estimated to affect a few thousand Americans, perhaps 4,000 or so.

In the experiments reported in Nature Medicine, mice carrying the human gene that were treated with ASC-J9 experienced a remarkable improvement. They were more mobile than their untreated counterparts, walking more normally and dragging their legs less often. Their muscles appeared to work normally, and they lived 40 percent longer than the untreated mice. In addition, the mice treated with ASC-J9 were able to mate and produce offspring, while their counterparts could not.

ASC-J9 appears to work by breaking up a sort of molecular clog in neurons affected by Kennedy disease. The biology of the disease is bit like Huntington's disease, a more common neurodegenerative disease that is inherited, fatal, and unyielding in its progression. Both are caused by an abnormal repeat of three nucleotides, CAG, though not in the same gene ?a kind of molecular stutter that results in extra copies of the amino acid glutamine.

In such diseases, the extra amino acids become part of abnormal proteins that clump up inside neurons, creating a clog that can bring normal molecular activity to a standstill. The clumps of material eventually become toxic to neurons.

In Kennedy's di
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Source:University of Rochester Medical Center


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