U. finds clues on 'Lincoln's disease'

A discovery by University of Utah researchers offers new thoughts on what causes a neurodegenerative condition Abe Lincoln might have suffered, had he lived longer.

The researchers used a gene that has been linked with Lincoln's descendants, many of whom have suffered a degenerative condition called spinocerebellar ataxia type 5 (SCA5), which slowly leads to paralysis. Their findings were published Monday in The Journal of Cell Biology.

SCA5 has been identified in 11 generations of the Lincoln family, starting with his paternal grandparents.

It has long been believed that many neurodegenerative conditions, including Huntington's disease and Parkinson's disease, are caused by cytotoxicity — a buildup of defective proteins in cells. The U. discovery suggests that in at least some conditions, the structural integrity of the neuron itself leads to degeneration, even to paralysis.

"In some ways, it's not too surprising," says professor Michael Bastiani, the study's senior author and staff member of the U. Brain Institute. He says boxers and other athletes who experience rapid physical acceleration and deceleration of their brains from blows might have neuro-degeneration. "We argue that it's actual physical trauma itself. Whether that can directly lead to therapies, though, is a long way away."

When someone moves, nerves stretch but don't break. The U. study suggests that a gene produces a "springy protein" that maintains the nerves' flexibility. When they disabled that gene in nematode worms, they found that nerve cells shatter. They looked at a worm gene that makes a protein called beta spectrin. Humans have four such genes, and a mutation in one of them was previously shown to be the cause of SCA5, which can develop in someone as young as 10 or as old as 68. It destroys the nerve cells in the section of the brain responsible for movement control; those with SCA5 may lose coordination and ability to walk, speak, write and swallow.

Earlier research elsewhere suggested the mutation prevents beta spectrin from holding other proteins where they belong in the cells, preventing normal cell communication. The U. research suggests that defective beta spectrin actually breaks the nerve cell, severing communication.

In a news release announcing the study, co-author and biology professor Erik Jorgensen said more research will be needed to settle that debate, since the mutant worms don't have the protein and patients with SCA5 have a mutated form.

The tiny nematode worms are often used for research on human disease because they are similar genetically.