(CHICAGO) - A team of international researchers led by Northwestern Medicine scientists has identified how a defective protein plays a central role in a rare, lethal childhood disease known as Giant Axonal Neuropathy, or GAN. The finding is reported in the May 2013 Journal of Clinical Investigation.
GAN is an extremely rare and untreatable genetic disorder that strikes the central and peripheral nervous systems of young children. Those affected show no symptoms at birth; typically around age three the first signs of muscle weakness appear and progress slowly but steadily. Children with GAN experience increasing difficulty walking and are often wheelchair-bound by age 10. Over time, they become dependent on feeding and breathing tubes. Only a few will survive into young adulthood.
In GAN patients, nerve cells are swollen with massive build-ups of structures called intermediate filaments, cytoskeletal components that give cells their shape and mechanical properties. Goldman's team found that gigaxonin, a protein encoded by the gene involved in GAN, regulates normal turnover of the protein building blocks that form a cell's intermediate filaments. Mutations in this gene result in the malfunctioning of gigaxonin, which leads to the abnormal build-up of intermediate filaments and eventually disrupts the normal functioning of nerve cells.
"This important new research pinpoints the mechanism that allows intermediate filaments to rapidly build up in GAN patients," says Robert Goldman, chair of the department of cell and molecular biology at Northwestern University Feinberg School of Medicine. Goldman has studied the structural proteins of cells for more than 30 years.
"This is a huge step forward for GAN research," said Lori Sames, co-founder and CEO of Hannah's Hope Fund, the leading GAN disease organization. "GAN is juvenile ALS, but even worse. Not only do motor neurons die out, so do the sensory neurons. To find a
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