In ALS Association-supported work published in the journal Neuron, researchers have announced the discovery of a new gene for ALS, which further implicates defects in the cellular transport system as a cause of the disease. A video abstract is available here.
The newly discovered gene, called TUBA4A, encodes the Tubulin Alpha 4A protein. This protein is part of the microtubule “cytoskeleton” of every cell, including motor neurons, the cells that die in ALS. Microtubules give structure to the cell and also transport many important molecules within the cell, including growth factors critical for neuron survival. Previous work has suggested that defects in microtubule transport of growth factors are a cause of neurodegeneration.
To discover the TUBA4A gene, the team looked for gene variations in more than 600 people with a familial form of ALS that was not due to known genes. They identified several variants in the TUBA4A gene in six ALS cases, and they showed in cell culture that these variants caused defects in microtubule structure and transport.
The new research was led by Vincenzo Silani, M.D., of the Istituto Auxologico Italiano in Milan, Italy; Christopher Shaw, M.D., of King’s College London; and John Landers, Ph.D., of the University of Massachusetts Medical School, Worcester, Massachusetts. Additional funding for the study was provided by the Motor Neuron Disease Association of the United Kingdom. Dr. Landers is also co-principal investigator for the United States arm of Project MinE, an international effort to sequence the genomes of at least 15,000 people with ALS, supported by The ALS Association.
“This discovery strengthens the evidence that transport defects in neurons can lead to ALS,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The Association. “Strategies to overcome those defects may provide a route to development of therapy. This new gene also presents us with an opportunity to develop a new disease model, which may reveal further targets for drug development, to mitigate the effects of this mutation.”