April 4, 2009 from Gene's blog at www.curehd.blogspotcom

Times are bad, but my wife and I have decided to borrow $75,000 to build a pool and fix up the house. It may sound crazy, but when you're faced with a devastating disease like Huntington's, it's important to enjoy life in the now. This is the topic of "In a time of crisis, the best investment of all," my latest entry in my blog. I'm now at the age when my HD-stricken mother started to show symptoms.

The HART clinical trial testing ACR16 in Huntington's began in October 2008 with its first participant. And as is usual, it has taken additional time to open all of the centers needed for this 220 person trial. But now with 17 centers actively recruiting, many participants are still needed to complete enrollment for this important trial. Overall, the HD community response to recruitment has been less than overwhelming. Why aren't we signing up in larger numbers? Why should we bother?

There is a straightforward answer: There will never be new treatments if we don't join clinical trials.

How safe are antipsychotic medications -- that most often include Risperdal, Zyprexa, Seroquel and Haldol -- in Huntington's? This is an especially important question to address following the publication of two separate studies in highly respected medical journals earlier this month addressing risks of these drugs.

Though these are different types of studies and neither specifically addresses antipsychotic drug use in Huntington's, the stark results: that antipsychotic usage increases the risk of death -- nearly twice as much in one of the studies -- prompted strong expert recommendations for limiting the use of these drugs to severe neuropsychiatric symptoms.

This article was posted last year, and I'm doing it again at New Years Resolution time. Let's all get off the couch. Physical exercise is important for everyone's general health -- but in Huntington's which is known to cause muscle abnormalities and weakness -- it is especially important for maintaining muscle strength and function.

There are studies in Huntington's people showing that physical activity programs give functional benefit, raise motor scores, and prevent falls. And recently a new study gives evidence that a more active lifestyle may slow progression of disease before symptom onset. For those with premanifest Huntington's, higher levels of physical activity correlated with delay in predicted onset of symptoms for as much as 4 years .

The Huntington Study Group (HSG) held its annual meeting in St. Petersburg, Florida November 12-14 2008 for clinical investigators and invited guests. These meetings culminated in the 2nd annual HUNTINGTON DISEASE CLINICAL RESEARCH SYMPOSIUM. The HSG meetings and the Symposium are unique research events because the single focus is clinical research, or that which is limited to human study.

The HSG Symposium is not only unique; it is -- by design -- a remarkably inclusive event. HSG leader Ira Shoulson purposely planned the symposium to be a place where researchers and patient families can sit side-by-side to learn from presentations and each other. As in the previous year, Huntington family representatives were included all the way from the beginning planning stages, to participation of more than 100 families in this year's final event.

After almost a 3-year FDA regulatory process, Xenazine (tetrabenazine) is finally here. The FDA approved this first drug for Huntington's because of broad agreement from the experts that it gives meaningful benefit to many whose lives are impaired by chorea. And in a careful move required by the FDA, Xenazine will be available only through a complicated prescribing process that is unique to this drug, which is intended to improve physician education and patient oversight that will address associated risks.

Xenazine will be made available through Ovation Pharmaceuticals. This review is based on information provided by David Knocke from Ovation, and Dr. Russell Katz from the FDA during the November, 2008 Huntington Study Group Meetings.

In the previous article (Neuroinflamation Part 1) we reviewed evidence reported by Bjorquist and colleagues for neuroinflammation in Huntington's, where the authors found elevated cytokine levels which increased with disease stage. We also reported on other studies and observations showing that inflammation --and correlating cytokine levels -- form a major component of progression in neurodegenerative diseases.

Building on this work, scientists in academia, CHDI, and other pharmaceutical companies are hard at work on drugs that target inflammation, and several candidate molecules have progressed to testing in mouse models. However, most of these candidate drugs -- whose safety is unknown -- target downstream mechanisms in the inflammatory process, or those that occur after cytokine release. Trehalose -- whose safety is well known -- works in a very early part of the process by inhibiting cytokine release. Might it be time to reconsider this agent for therapeutic development?

In the July, 2008 Journal of Experimental Medicine Dr M. Bjorquist, S. Tabrizi and collaborators reported on their findings of immune activation and inflammation in Huntington's. They showed that several inflammatory markers called cytokines are found very early in the disease process and strongly correlate with disease progression. These findings are valuable to Huntington families because cytokines may become important biomarkers; and even more importantly this work adds to the growing evidence that inflammation is a highly important disease mechanism, which in turn makes it a key pathway for drug targeting.

The full article detailing results of Repligen Corporation's HDAC 4 inhibitor drug candidate was published in the jounal Proceedings of the National Academy of Sciences (PNAS). Scientists from Repligen and the Scripps Institute in California detail exciting results from study of their drug candidate in the R6-2 mouse model. So far, it is looking good . .

In the recent HDDW article "Lighting the Candle" of clinical trials for Huntington's, we placed emphasis on the work of HSG, CHDI and other sponsors. Of course they are all important, but in the end the most vital part of clinical trials belongs to the Huntington family community: It will be us who keep the flames alive.

Because no matter who lights the candle, even the best drug candidates, or the most improved clinical trial designs, or the perfect biomarkers -- all of these things will make no difference -- if we don't support and join clinical trials. Here's how to begin . .