October 17, 2007

New Studies Support ALS-Angiogenin Connection

A study conducted by investigators at several institutions in Boston has added additional support to an existing hypothesis based on earlier studies that mutations in the gene for angiogenin can cause amyotrophic lateral sclerosis (ALS) or at least increase susceptibility to the disease. Angiogenin is a protein that participates in the formation of new blood vessels (angiogenesis).

David Wu at Brigham and Women’s Hospital, with colleagues at Harvard Medical School and Massachusetts General Hospital, identified mutations in the angiogenin gene in four out of 298 North American ALS patients whose DNA had previously been screened and found not to contain ALS-causing abnormalities in a gene called SOD1.

Wu and colleagues, reporting online Sept. 20 in Annals of Neurology, said the four variants they identified all cause a complete loss of function of the angiogenin protein.

A deficiency of the protein known as vascular (blood-vessel) endothelial growth factor (VEGF) has also been implicated as a possible ALS susceptibility factor, and angiogenin works in the same biological pathway as VEGF.

In their paper, the researchers speculated that the role of angiogenin in protecting neurons may extend beyond its effect on blood vessels that support these cells.

On Oct. 4, Vasanta Subramanian and colleagues at the University of Bath, United Kingdom, announced online in Human Molecular Genetics their findings that angiogenin is involved in maintenance of motor neurons and in the growth of nerve fibers, and that three ALS-associated angiogenin variants were toxic to lab-grown motor neurons.