Drs. Kim and Guy Caldwell have a patent pending that has implications on the treatment of neurological disorders.

TUSCALOOSA, Ala. - Laboratory tests at The University of Alabama indicate a protein typically coded within human DNA can suppress the potentially harmful clumping of other proteins, a discovery that has implications in dystonia, Parkinson's disease, and other neurological disorders.

The discovery, the culmination of an effort led by Dr. Guy Caldwell, assistant professor of biological sciences in UA's College of Arts and Sciences, is featured as the cover story in the Feb. 1 issue of "Human Molecular Genetics," a top-ranked human disease research journal. The Dystonia Medical Research Foundation funded the efforts leading to the report. Caldwell also is supported, in part, by a grant from the Howard Hughes Medical Institute.

Caldwell, his wife, Dr. Kim Caldwell, an adjunct assistant professor of biological sciences at UA, and The University of Alabama have a patent pending on the finding, as well. "We're actually patenting something that you and I have in our DNA, but we're patenting it for a therapeutic purpose," Guy Caldwell said. "Many diseases of the nervous system involve aggregates, or clumps, of protein forming in our cells. If you were to look into the brain of a Parkinson's patient after they died, you would see they have clumps of proteins called Lewy Bodies," he said.

Proteins must fold properly within cells to function correctly, Caldwell said. One misfolding can lead to others and, subsequently, to aggregation. Aggregation can lead to neuron malfunction or cell death.

A specific gene, known as TOR1A (or DYT1), has been linked to the most severe form of dystonia. This gene contains the information to make a protein called torsinA. Caldwell's lab has solved the mystery of torsinA's cellular function, which was previously unknown.

"Torsins appear to be involved in a cellular mechanism responsible for the management of proper protein folding," Caldwell said. "When that mechanism goes awry, it results in protein aggregation. Thus, functional torsin proteins seem to serve in a protective capacity within cells."

Caldwell uses a transparent, microscopic worm, known as C. elegans, in his research. This tiny animal has garnered international attention recently as the subject of the 2002 Nobel Prize in Medicine. Caldwell's lab exploited this organism to generate a system by which a protein from jellyfish -- the protein that causes them to glow -- could be transplanted into C. elegans and artificially induced to aggregate or clump.

In the laboratory, adding torsinA significantly reduced the fluorescent protein clumps in the worm. "This is a protein that can suppress intra-cellular aggregation of proteins," Caldwell said.

To expand upon these results, the Caldwell Lab genetically engineered a fusion between this jellyfish protein and a human protein, alpha-synuclein, that is directly implicated in Parkinson's disease. "Preliminary data indicate that torsins are equally effective in suppressing alpha-synuclein aggregation in worms."

The ability to transfer this knowledge into therapeutic measures for humans would come from the biotechnology and pharmaceutical industries, Caldwell said.

"We're providing the lead -- we've identified the function of this protein."

Approximately 50 percent of all human hereditary diseases, including dystonia and Parkinson's disease, have been linked to genetic components also found in C. elegans, Caldwell said.

"The worm's nervous system has been completely mapped and contains only 302 neurons, in contrast to the 100 billion neurons located in the human brain, alone," Caldwell said. "This makes it easier to trace the pathways of the worm's neurons and trace its protein functions within the neurons and related cells.

"All the typical hallmarks of the human nervous system, such as neurotransmitters like dopamine and serotonin, are present in this worm," Caldwell said. "It also has rapid responses which, since it's transparent, can be easily examined, and it allows you to identify additional genes that may be involved in a similar process."

Recently, the Michael J. Fox Foundation announced it had named Caldwell's group one of only 11 labs in the world selected for its Protein Degradation Grant Program. Through it, he will receive $145,000 in funding over a two-year period allowing him to advance his research into the central nervous system disorder estimated to affect 1 million Americans.

Caldwell's research efforts have also drawn support from the March of Dimes, the National Science Foundation, the National Parkinson Foundation and the Parkinson's Disease Foundation.

The Dystonia Foundation was founded in 1976 by Samuel and Frances Belzberg, of Vancouver, Canada, after their daughter was diagnosed with dystonia. Dedicated to serving the needs of all persons affected with dystonia and their families, the Dystonia Foundation has grown from a small family-based foundation to a membership-driven organization of close to 32,000 persons. Its mission is to advance research for more treatments and ultimately a cure; to promote awareness and education; and to support the needs and well being of affected individuals and families.

The College of Arts and Sciences is UA's largest division and the largest public liberal arts college in the state, with approximately 5,000 undergraduate and 1,000 graduate students. The College has received national recognition for academic excellence, and A&S students have been selected for many of the nation's top academic honors, including 15 Rhodes Scholarships, 13 Goldwater Scholarships, seven Truman Scholarships and 11 memberships on USA Today's Academic All-American teams.