The ups and downs of waiting for a cure

Waiting for news of an effective treatment or a cure is one of the most nerve-wracking aspects of living at risk for Huntington’s disease.

When I first learned of my mother’s illness in late 1995, optimism flowed in the HD community. Just two years before, scientists had discovered the HD gene. That monumental achievement made a simple and definitive test for HD possible. It also opened the door to new avenues of research. Within a few years, for instance, researchers identified the protein produced by the gene known as huntingtin.

I remember reading an article stating that it would take only a couple more years to begin human testing for a drug designed to stop the protein from plying its harmful effects on brain cells. My wife and I felt confident that a cure would come before my symptoms ever started.

In the ensuing years new discoveries came not on an annual basis, but almost on a monthly one. But as time went on, the predictions of a quick solution to HD disappeared. The disease and its causes were proving to be far more complex than anybody had imagined. Initial hypotheses were overturned. For example, scientists long believed that clumps found in the brain cells of HD patients were the main culprit in cell death. Most recently, however, researchers have demonstrated that those clumps actually protect the cells.

One of the most disheartening comments came in 2003, when an article in a Huntington’s Disease Society of America (www.hdsa.org) publication stated that a successful treatment was still a decade off. That statement angered me and others in my local HD community. Maybe something might arrive around the year 2012, but what about the many at-risk individuals (like me) who had been waiting so many years for the key breakthrough? I was now convinced that I would become ill before a treatment arrived.

It was about that time that I and others began paying attention to Huntington’s Disease Drug Works, an alternative organization (http://hddrugworks.org). HDDW does not deny the value of long-term research but also emphasizes a “treatment now” approach using existing medications and dietary supplements demonstrated to be safe in humans and effective in slowing HD in animals. But this is not the cure we have all been waiting for.

Scientists have now identified numerous substances that can arrest HD in test tubes or animal models. Several firms and researchers have done so by focusing on a way to stop the huntingtin protein. This approach was the “magic bullet,” the way to stop the disease before it could harm brain cells. But research is still a long way from getting those substances safely into the human brain.

Then in 2002 came a stunning discovery called RNA interference (RNAi), a naturally occurring process. Simply put, this technique can regulate and turn off harmful genes. Late last year scientists already began testing RNAi in human patients suffering from an eye condition called macular degeneration, a potential cause of blindness.

Just this month researchers at the University of Iowa used RNAi to reduce the levels of huntingtin in transgenic mice ill with HD (click here to read more). The levels of the toxic protein fell by about 40 percent, and the mice demonstrated nearly normal movement and less neurological damage.

Given these developments, it appears that a cure must come! But over the years, as I have swung between optimism and pessimism, I have come to appreciate the many nuances of the HD disease process and the intricacies involved in trying to stop it. I am encouraged, even electrified, when I read about such breathtaking developments as RNAi. But I am also sober after so much waiting.

And, at the end of the day, after doing all that I can to help raise awareness about HD, waiting is all I can do. Being at risk for HD, I am humbled, patient, and aware that my fate lies in the hands of those dedicated scientists putting in long hours in the lab.

And when I awake the next morning, I start thinking again about how to help raise funds to accelerate their progress.