Science and Research Panel
By Julie Stauffer

Once again, we lined up an impressive team of researchers at the Huntington Society's Annual Conference to update us on the latest scientific discoveries and clinical advances. Each year it's inspiring to learn how much progress is being made in the fight against HD, and 2003 was no exception.

In this issue of Horizon, we'll focus on presentations from two members of this year's Science and Research Panel: Chris Gregg and Dr. Oksana Suchowersky. Look for highlights from Dr. Susan Andrew's presentation in our Spring issue.

Chris Gregg: Growing New Brain Cells

For many years, scientists believed that the brain couldn't make new cells - any cells that were destroyed, they thought, were gone forever. Today we're seeing lots of exciting research that shows it is possible to make new brain cells, and that's clearly good news for the Huntington's community.

Chris Gregg is a graduate trainee in Dr. Sam Weiss's neuroscience lab at the University of Calgary, where they are working with something called neural stem cells - cells that can grow and divide to create new brain cells.

A graduate student named Brent Reynolds first discovered these neural stem cells in 1992. He found that if he put cells from a certain part of the brain in a Petri dish and added a hormone called epidermal growth factor, he could grow a whole cluster of cells. After the cell cluster formed, removing the epidermal growth factor made the cells mature into adult brain cells. This was quite a breakthrough.

Next came the big question: could they find a way to use these stem cells to generate new cells that would replace damaged or diseased brain tissue?

Working with rats, Gregg's lab has shown that a cocktail of two substances - epidermal growth factor (EGF) and erythropoietin (EPO) - can do the job. EGF encourages stem cells to grow and divide and move to the damaged part of the brain. EPO also encourages the new brain cells to move to the damaged area, and it makes them specialize into the right kind of tissue.

In these experiments, the researchers surgically damaged part of the rats' brains to mimic the effect of a stroke. A healthy rat uses both paws equally, but after the surgery, the "stroke-damaged" rats lost the ability to use their left paws.

Now comes the exciting part: if these rats were treated with the cocktail of EGF and EPO, they were able to use both paws equally once again. When the researchers examined the rats' brains, they found that new tissue had formed to replace the damaged part. And if they removed that new tissue, the rats lost their ability to use their left paws.

Currently Gregg's lab is just beginning to test their cocktail on a Huntington's model - a mouse with damage to the striatum, which is one of the areas of the brain that is destroyed by HD.

We won't know the results for two to five years. "It's slow," he acknowledges, "but these things take a long time." With any luck, though, the results will be good, and the EGF/EPO cocktail will be just as effective in healing the Huntington's mouse as it is in healing rats with stroke damage.

Dr. Oksana Suchowersky: A Cornucopia of Clinical Trials

Dr. Suchowersky is a neurologist at Calgary's Movement Disorders Clinic and a professor of Clinical Neuroscience and Medical Genetics at the University of Calgary. Her talk focussed on the clinical trials organized through the Huntington Study Group (HSG), which is an international collaboration with study sites around the world.

"We have a lot of things on the go," says Dr. Suchowersky, and it's clear she's not exaggerating - in her talk she highlighted seven HSG trials that are happening, just wrapped up or will be beginning shortly. Here's the scoop:

CARE-HD
The CARE-HD trial recently ended. Its purpose was to examine whether coenzyme Q10 and remacemide could slow down the progression of HD, and unfortunately the results weren't as good as everyone has hoped for. After 18 months, patients taking remacemide had a little less chorea, and the patients on coenzyme Q10 seemed to show a little less progression. However, the results were not statistically significant, and more studies will be needed to make sure it was a real effect. As remacemide did not help significantly, the HSG will not be working with it anymore.

A much larger study of coenzyme Q10 is now in the works to find out whether it really is helpful in slowing down the progression of HD. It will probably begin next year, says Dr. Suchowersky.

MINO-HD
A small MINO-HD trial is currently underway to test the effects of minocycline, which may slow down the progression of Huntington's symptoms. It is one of the antibiotics that dermatologists use to treat acne, and because it's been used on teenagers for a number of years, we know that it is reasonably safe.

However, minocycline can cause problems with dizziness and imbalance, so HSG is testing it on a small number of patients to see whether it has any side effects or any benefits before moving to a larger study. Stay tuned for the results.

UHDRS Database
One of HSG's major undertakings is to develop a database to track the progression of HD in a large number of patients. It uses the UHDRS - Unified Huntington Disease Rating Scale - a series of tests to evaluate HD symptoms. If your neurologist has ever asked you to look this way, do this, and stick out your tongue, you'll know all about the UHDRS.

The database will be important, says Dr. Suchowersky, because by knowing how HD symptoms normally progress in lots of patients, researchers will be able to judge how well new medications work.

PHAROS
PHAROS (Prospective Huntington At Risk Observational Study) is a big trial currently underway which looks at people who are at risk for HD and do not know or want to know whether they carry the HD gene. The purpose is to find out what the first symptoms are and to improve doctors' ability to detect these symptoms. Dr. Suchowersky reported that enrollment in PHAROS has just closed, and she thanked everyone who is participating in it.

PREDICT-HD
HSG is currently looking for volunteers who have the HD gene for PREDICT-HD, a large study that involves a lot of detailed clinical observations, MRI tests and neuropsychological testing. The purpose is to find out what the first symptoms of HD are, which will be very important when drugs are found to slow down the progression of the disease. Dr. Suchowersky encouraged anyone who is interested to participate in this trial.

TETRA-HD
In the United States, HSG has just launched clinical trials of tetrabenazine, a drug that decreases chorea. It has been used in Canada for 20 years, but not the US.

On the Horizon
There's a lot of very exciting research being done in labs around the world, and HSG is working closely with these basic scientists. As soon as something looks promising in mice or fruit flies, HSG will develop a human trial to see whether that substance works and whether it's safe in humans. That's when people with HD and people at risk can play an important role, by volunteering for clinical trials to see whether new therapies are effective or not.

Dr. Suchowersky finished by emphasizing the importance of the support we provide. "HSG could not do what it's doing without the support of the Huntington Society of Canada," she explained, "and I'd really like to thank you for that."