MDA awarded a research grant totaling $420,000 over three years to professor Garth Nicholson at the ANZAC Research Institute, University of Sydney in New South Wales, Australia.

The funds will help support Nicholson's research into the biological and cellular effects caused by mutations in the copper transport gene ATP7A in Charcot-Marie-Tooth disease (CMT).

Nicholson and colleagues have discovered that mutations in the copper transport gene ATP7A cause slow but progressive degeneration of the long ends (axons) of the nerve cells called motor neurons that send signals to the limb muscles.

The ATP7A protein is essential for human copper metabolism; it is involved with the delivery of copper for physiological processes, and also in maintaining copper balance in humans.

Nicholson's team has shown that mutant ATP7A protein does not traffic copper properly in the presence of elevated copper levels. Now it plans to determine whether ATP7A mutations cause disease symptoms by a mild reduction in intracellular copper movement from motor neurons, or whether the mutations work by some other mechanism such as poor delivery of copper to the distal axon, due to the trafficking defect.

Using human cellular and research mouse models, the investigators plan to determine the biological and cellular effects of the impaired ATP7A trafficking. They will investigate the role of interacting proteins in ATP7A trafficking relevant to axonal copper delivery as a means of exploring the possible mechanistic links between motor neuron disorders and copper; and they will establish a transgenic mouse model that carries mutations in the ATP7A gene.

Funding for this MDA grant began February 1, 2012.