The Huntington Society's Annual Conference in Niagara Falls was fortunate to have presentations from three Huntington disease researchers: Dr. Eileen Denovan-Wright, Dr. Ray Truant, and Dr. Marcy MacDonald. Included below are summaries of their speeches.

Dr. Denovan-Wright provided an excellent overview of the Society's research program, including the key factors in its ongoing success. She highlighted the membership of the Society's Research Council, which is strategically composed of not only leading researchers in Canada, but also from abroad (such as Dr. Gillian Bates at Guy's Hospital, London, England) and from the private sector (Dr. Sophie Roy, Merck Frosst Centre for Therapeutic Research).

Of particular interest to the audience were Dr. Denovan-Wright's comments about how the Society grants money to research. There were two strengths to the NAVIGATOR program that she highlighted. The first was how the Society funds both basic and clinical research, the all-important balance between "lab bench and bedside".

The second point she made related to how the Society's research dollars are split amongst multiple researchers and labs. "In the long run, it makes more sense to spend smaller amounts of money on a number of research brains than to spend lots of money on just one or two research brains." She pointed out that there are numerous examples of how the Society has been able to support and sustain the research efforts of scientists with small amounts of money. One of the best things that the Society is able to do is provide money that allows researchers, who are trying to keep their labs active in between the arrival of larger grants from funders like the Canadian Institutes for Health Research (CIHR), to continue ongoing research without having to shut down until larger grants actually arrive.

According to Dr. Denovan-Wright, solving the puzzle of Huntington disease is an international problem, and one in which the Huntington Society of Canada is currently playing a key role.

Using a LCD projector connected to his laptop computer, Dr. Truant "wowed" the audience with timelapsed video images of toxic protein aggregates actually forming in a brain cell, and then killing it.

Dr. Truant is trying to understand how and why the toxic protein huntingtin (created by the mutant gene that causes Huntington disease) enters the nucleus of brain cells, and to find out what effect, if any, preventing huntingtin from entering the nucleus of a brain cell has on the process of cell death in Huntington disease. Using two very sophisticated microscopes (one worth roughly $400,000; the other $250,000), Dr. Truant has been able to observe the mutant huntingtin at work in live neurons (brain cells). His work is tremendously important in understanding how the mutant huntingtin functions and interacts with other proteins in brain cells.

Dr. Truant also took the time to acknowledge the importance of funding support such as the NAVIGATOR Coalition grant he received from the Huntington Society of Canada. "Labs like mine can't function without the support of organizations like the Huntington Society."

The keynote speaker for the research forum was Dr. Marcy MacDonald, who started her presentation by recalling her first meeting with the Society's founder, Ralph Walker. "Ralph Walker actually recruited me. I met Ralph at a meeting, and he said, 'You don't sound like an American,' and I said, 'Well that's because I am not an American, I'm from Northern Ontario … I was born in Larder Lake.' And so he said, 'I'll tell you what, you can stay in the U.S. but you have to work with us.' And I said, 'Ralph, whatever you want!'"

Dr. MacDonald talked about the search for a cure for Huntington disease being a cycle that can be broken down into four parts:

• the first part of the cycle is developing a good description of the disease that can guide research
• the second part of the cycle is identifying the genetic cause of the disease so that researchers can know what the real problem is
• the third step in the cycle is to describe and understand how the mutant huntingtin protein actually leads to the death of brain cells in patients with HD
• and the last phase of the cycle is actually developing something that makes a difference in the lives of people who have HD.

Today, research is on the third cycle, leading into the fourth. As she talked about each part of the cycle, Dr. MacDonald talked about what we already know about Huntington disease, and highlighted what researchers don't know but are working hard to figure out. But there were a couple of key points that she made that the Huntington's community in Canada should make note of.

CAG expansion and age of onset

"For any given individual, it's very difficult to accurately predict exactly when onset will happen. And this is for a very important, very hopeful reason." If one CAG repeat length can result in a twenty-year range for onset of symptoms to occur, there must be other factors that have a bearing on when symptoms will start. In Dr. MacDonald's opinion, "That means that there are genes and there are drugs and there are environmental things that are going to be able to go into the equation and have a say in when the disease will start. That's very helpful … good genes versus bad genes, healthy lifestyle versus unhealthy lifestyle, or just plain good luck versus bad luck…this tells us we are going to be able to modify age of onset."

What does this mean?

Dr. MacDonald is saying that there are a lot more factors than just CAG repeat length that determine when onset of symptoms will occur. Some of these factors are environmental - eating well, exercising, minimizing stress, trying to stay involved in things around you. Each of these could be a way of delaying onset of symptoms.

We don't need to do big things to produce big results

Dr. MacDonald pointed out that the difference in a mutant gene that produces toxic huntingtin and the normal gene is incredibly small. She added, "That's a pretty subtle difference, and the fact that it's very subtle means if we could figure out how exactly the new mutant protein is working we'd have a pretty good shot at shifting what it's doing. Because what it's doing is not dramatic."

In Dr. MacDonald's favoured scenario, the key is to discover the first thing that mutant huntingtin does in the cell that sets off the chain reaction of all the other bad things that lead to the death of the brain cell. "It means that if we can interfere with the mutant huntingtin protein and the first thing that it triggers in the cell, we have a chance at stopping things before there are a lot of downstream consequences to have to deal with."

People with HD can be helping themselves now

"Environmental enrichment is when you take an HD mouse model - and these are very, very sick animals - and you give them stuff to play with in their cages. You give them toilet paper rolls, pieces of plastic and little wheels and stuff to kick around - things to make their lives more interesting - and it increases their survival the same as mice on minocycline, the same as creatine, the same as other drug treatments. I think that is a powerful message…it means that having a good day might make the difference."

What does this mean?

Research has shown that mice with HD who are encouraged to live well - eat well, sleep well, exercise, etc. - live longer than mice with HD who don't do these things. In fact, according to Dr. MacDonald, the positive impact of these activities is at least as effective in slowing progression as mice with HD who are given creatine or minocycline.

Treatment will be a reality

"I want to leave you with a thought that Eileen and Ray also left with you, which is that things have moved lots faster than any of us can possibly believe, and we have generated things that say it's absolutely possible to defeat this disease."