From Cloning the Gene to Finding a Cure
Dr. Susan Andrew's presentation at the 2003 Annual Conference
By Julie Stauffer

In the last issue of Horizon we reported on two of the presentations from 2003's Science and Research Panel. The final panelist was Dr. Susan Andrew, an assistant professor of medical genetics at the University of Alberta.

The Huntington Society of Canada began funding Dr. Andrew when she was a Ph.D. student in Dr. Michael Hayden's lab. Today HSC continues to fund the important work she's doing on DNA repair proteins and CAG repeats. Rather than talk about her own research, however, Dr. Andrew focused her presentation on the impressive advances in HD research that have occurred recently.

The first breakthrough she described was the development of a rat model of HD. Animal models are essential for studying the function of the HD protein and for testing potential treatments before we try them in humans. For example, we've tested the antibiotic minocycline in mice. The results were promising - minocycline delayed cell death and the onset of disease in these animals without any harmful effects - so now we've launched human drug trials, which are currently ongoing. Although we have many mouse models of HD, a rat model will be even more helpful in screening drugs to delay onset of Huntington's because we know much more about the rat brain and rat behaviour than we do about mice.

In 2003, we learned a lot more about how the HD protein affects brain cells. One of the keys to normal brain cell function are organelles called synaptic vesicles, which contain neurotransmitters that relay messages from one brain cell to another. New research revealed that HD brain cells have fewer synaptic vesicles than normal cells, and mutant HD protein prevents them from properly releasing their neurotransmitters.

We also learned more about the factors that influence the age of onset of HD. We knew that the more CAG repeats someone has, the earlier HD is likely to strike. However, this is only half the story. Studies have now identified three new chromosomal regions that play a role. The next step is to identify the culprit genes in those regions, which will hopefully provide clues to delaying or preventing the onset of disease. With data from the Human Genome Project, says Dr. Andrew, it will not be long before these key genes are identified.

A promising treatment for Huntington's was discovered accidentally when researchers realized that a scientific dye called "Congo Red" could prevent the HD protein from binding to itself and triggering cell death. More experiments showed that Congo Red helped HD mice to live longer with fewer symptoms. Researchers are now trying to alter the dye so it can cross the blood-brain barrier for studies in humans.

Finally, Dr. Andrew talked about RNA interference: an exciting new way to stop the expression of a specific gene. RNA is an intermediate between DNA and protein. Special RNA can be designed to bind to the HD RNA, preventing it from translating DNA into protein. This can shut down the mutant HD gene without silencing the normal HD gene, which we know is essential to brain cell survival.

Stopping HD is an uphill battle, she concluded, but we've come a long way in understanding the disease. When Dr. Andrew was born in 1965, 10 papers were published on HD.

Today there are more than 5,000 peer-reviewed papers on Huntington disease. Today researchers are focussing on the functions of the normal HD protein and which of these functions the mutant HD protein has lost. Another important question is why cell death only occurs in certain parts of the brain. Above all, scientists in laboratories around the world are working to discover what can be done to prevent or delay brain cell death in Huntington's.

"2003 was a year of successful landmark discoveries into HD, with further inroads on therapies actually shown to delay onset and/or reduce cell death," said Dr. Andrew. "I hope 2004 will bring even more momentous discoveries and a cure for this disorder."