From: Dr. Vicki Wheelock, Prof. of Clinical Neurology, Director of HD Clinic, UC Davis

I have just retrieved the e-mails re: EPA after returning from the American Neurological Association meeting last week in Boston. I had the opportunity to discuss with several other HSG members the dilemma that you pose. On the one hand, we have a disease for which there is currently no accepted treatment. On the other, we have preliminary evidence in a very small pilot trial that EPA may be helpful in HD; we also have reason to think that minocycline might be helpful. As you know, we are going to find out in a year or so whether CoQ10 and ramecemide are worthwhile or not when CARE-HD wraps up after 3 years. Should we go ahead and prescribe these medications in an open-label, uncontrolled fashion? We have no idea how safe they are, but on the other hand we already know how relentless HD is.

For a number of reasons, it takes years for drug trials to be completed. The reasons are complex, but most have to do with ethical and scientific oversite put in place both nationally through FDA and the NIH, and locally through institutional review boards. This oversite is put in place to protect patients from harm caused by unanticipated side effects or unscrupulous investigators. Please remember also that people with neurological disorders may have a diminished capacity to understand the balance between risks and benefits, and the oversite agencies must insure that these potential research subjects are not in some way exploited. Furthermore, well-designed trials require enormous funding, and competition for funding is intense.

Having said that, I personally cannot recommend EPA at this time as a treatment for HD. The formulation is not FDA-approved or regulated, and there have been serious problems over the years with purity of dietary/herbal supplements leading at times to serious illness or death (comfrey teas causing acute liver failure, contaminated amino acid supplement causing eosinophilic myositis are 2 examples). Furthermore, rapid-throughput screens of various substances in HD transgenic mice showed some benefit at one dose and accelerated the disease at another dose (presented at HSG meeting by Dr. Flynt Beal in Nov. 1999).

Minocycline is different in that it already has an FDA-approved formulation in the US, so purity is not an issue. However, how much should humans take? Are people with HD more or less susceptible to its side effects? Are there any different side effects in HD than in patients with other indications? Any toxicities from prolonged use? Can it be potentially neurotoxic at some doses? Finally, if everyone with HD is taking it, how will we find enough subjects to enter controlled clinical trials in the future?

There are a number of trials now going on or starting soon that will investigate the safety and tolerability of potential therapies in HD including creatine and EPA. HSG is moving ahead as quickly as possible with these studies, and if safety is established, then large-scale trials will undoubtedly follow. Other investigators outside of HSG will probably also continue to advance the science. Terry and I will be attending the 8th annual HSG meeting this week and will have more information to report to you afterwards.
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