THE HUNTINGTON TRAIN TO GLORY Connecting HD people to HD research

T he path from research to effective treatment for Huntington's disease is like a train on a track. Scientists built this train, with support from hard-working Huntington's organizations along with the sweat and tears of many HD families. Borrowing from Woody Guthrie's eloquent lyrics, this Huntington's train is truly bound for glory. The research engine has been fired up with explosive energy as more is learned about the biology of this disease in several model systems. This train has gathered speed as first one, then several drugs and agents have been found which partially treat the disease in mouse models. Scientists believe that drugs which are therapeutic in the mouse have the highest chance of success in people.

But therapeutic response is much easier to study in HD mice than in HD people. So despite growing momentum and strong effort, the Huntington's glory train has not yet been able to get over the hill from research to people with even a single recommended treatment. So this is the time and place for Huntington's Disease Drug Works (HDDW) to start its work. We'll bring the tools we already have (available drugs and agents) and put them together with the motivated workforce of HD people. We can traverse the hill between research and therapy for HD. We can do it for this generation.

HUNTINGTON'S DISEASE DRUG WORKS (HDDW) STATEMENT OF PURPOSE
HDDW INDIVIDUAL THERAPEUTIC TRIALS (ITT)

The primary objective of the "HDDW Individual Therapeutic Trials" (ITT) is to facilitate a medically supervised and personal best treatment plan for the person with Huntington's disease. It is known that many people with symptomatic Huntington's disease as well as many asymptomatic individuals "at risk" are taking drugs and over-the-counter agents that have been shown beneficial in genetic models of this disease. HDDW's primary objective in the ITT endeavor is to bring both of these HD groups, asymptomatic and symptomatic, to observed and supervised care while taking these drugs.

HDDW will partner with each participant's primary care physician. Each therapeutic trial will occur at this primary medical site, where, if estimates by Huntington's organizations are correct, more than 90% of HD individuals and families already receive medical care. As such a beneficial component of these trials is the updating of HD education to medical providers at this important site of care. For its part, HDDW will promote drug availability. We will use only FDA approved drugs and available over-the-counter agents, as well as edible natural products in these therapeutic trials.

A secondary HDDW objective for the individual participant is to measure and compare potential disease-modifying activities of drugs or agents used over time. HDDW will be responsible for monitoring and coordinating disease progression measurements, which will in turn, be supplied to the primary care physician for medical decision making. It is HDDW's hope that sequential information obtained in this manner will provide the participant and primary physician ability for improved decision making and will promote the best personalized medical care for the individual.

To limit interference with Huntington Study Group (HSG), HDDW will make every attempt not just to inform, but to encourage participation for those HD individuals who fit inclusion criteria for HSG studies. Likewise we will utilize great care in selection of drugs within geographic areas where similar drug studies are planned or ongoing. Of course, this HDDR goal can only be met if HSG and other organizations keep us informed of planned studies.

HDDW Disease Measurement Tools

The research measure of disease progression utilized in Huntington's patients is the Unified Huntington's Disease Rating Scale (UHDRS). Because frequent UHDRS testing is not possible in the usual office setting, another secondary objective of HDDW therapy trials is to define an appropriate set of measures that can be used in the primary care setting and correlate as best as possible with UHDRS. For this purpose, HDDW will provide each trial participant (who must also have a dedicated helper) with web-based and centrally organized tests for motor, cognitive, behavioral and functional capacity components. Serial results will then be supplied (in readable form) to each participating physician, who may in turn supply this information to the individual. It is the HDDW goal that these measures can reproducibly be used in the medical office setting to assess individual patient response. It will be the individual participant's rate of disease progression, and specifically not the average of the group population that is to be the measured and reported to the treating physician.

A tertiary HDDW objective is to design the individual's treatment care plan so that if sufficient numbers of individuals participate in such care plans, we may be able to generalize treatment results to the larger population of Huntington's in a statistically sound manner. Therefore, the study will be designed from the onset to best capture such results. When HDDW statisticians determine that group results are significant, this result will be made immediately available to all trial participants and their physicians. These results, whether positive or negative, will also be immediately posted on the HDDW website in a manner that will protect confidentiality of participants.

Guarding participant confidentiality and ensuring participant safety is paramount to HDDW. Institutional Review Board (IRB), and Health Information Privacy and Protection Act (HIPAA) guidelines will be adhered to and enforced during all individual trials.

Lastly, HDDW is hopeful, but of course can not guarantee that these trials will be successful for an individual or that the data obtained will be useful to the larger population of Huntington's people. No drug proposed for these trials has been proved to be beneficial in people. But at the very least the HDDW trial design will accomplish the primary goal of bringing individuals to supervised medical care. It will also create and sustain a ready and willing reservoir of Huntington's people with known disease progression measurements with known and documented drug history.

We at HDDW believe hope is a good thing. And further, we at HDDW believe this hope has a sound scientific base. We believe there is reasonable chance that a one or more of these drugs, either alone, or in combination will be beneficial either for an individual, a small group, or the larger population of Huntington's people. Further, even if successful, we believe that none of these agents alone or in combination are likely to result in a cure. So even if successful agents are defined, the treatment of Huntington's will be similar to other chronic diseases; with the need for long term therapy. In this case, HDDW participants would be well positioned to enter trials of experimental drugs coming down the research pipe-line.