HD Lighthouse Editors Comment: This is an update on the "Bile Acid Treats HD" and "TUDCA Dose, Safety" articles. Dirk Keene has kindly responded to some question we have about this new treatment for HD.

It is extremely encouraging that the treated animals were indistinguishable from control animals without the expanded HD gene.--Jerry

Posted to HDLighthouse: 11-Oct-01 [an error occurred while processing this directive] HDL Update: Tauroursodeoxycholic Acid (TUDCA) in HD: TUDCA Research Progress

"We are very interested in translating this research to the clinic, and will continue to pursue this as our ultimate goal." C. Dirk Keene, From Dr. Walter Low's laboratory at the University of Minnesota Medical School

Hi Mr. Lampson,

My name is Dirk Keene, and am an MD/PhD student in Dr. Walter Low's laboratory at the University of MN. I wanted to respond to your email to Walt regarding our paper describing the effects of the bile acid TUDCA in the 3-NP rat model of HD. First, we really appreciate your interest, as our goal is, as is yours, to ultimately develop therapies that will be useful for HD patients. As you may know, the paper is now published in Experimental Neurology, but I can directly address the questions you raised.

First, TUDCA was delivered to the rats intra-peritoneally on a daily basis, although UDCA (which is also effective in HD tissue culture studies) is commonly administered orally for cholestatic disease. While we haven't done any oral dosing studies, we are interested in this investigation. Furthermore, the BBB is quite permeable to TUDCA, and we found levels up to sevenfold higher than controls in chronically treated rats.

Patients typically receive 8 to 10 mg/kg of UDCA per day orally. As you can see, the TUDCA dosage we used (50 mg/kg/day, i.p.) is significantly higher. However, TUDCA (as well as UDCA) exhibits extremely low toxicity, and our dosage was primarily determined by the solubility of the drug (we chose TUDCA over UDCA due to it's increased solubility). In addition, we noticed no side effects. Behavioral and physiological parameters were monitored in a pilot dosing study and in the reported study, and, aside from a slight peritoneal discomfort lasting less than a few minutes, treated animals were indistinguishable from controls.

As for clinical trials, as an MD/PhD student I would love to see my work translated from the bench to the clinic. However, we feel there are certain experiments that need to be conducted prior to human studies. First, we must determine the efficacy of TUDCA in preventing genetically mediated neurodegeneration (i.e. transgenic mouse HD models). These studies are ongoing and are yielding promising results. In addition, we must determine the optimal TUDCA dose and delivery in the animal models prior to clinical applications. We are very interested in translating this research to the clinic, and will continue to pursue this as our ultimate goal.

Hope this is helpful. Take care and thanks again for your interest.

Sincerely,

C. Dirk Keene

Source: From Dr. Walter Low's laboratory at the University of Minnesota Medical School

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