Ursodiol is a FDA approved drug available by prescription only. It is used for dissolving cholesterol stones in the gall bladder, and in the treatment of certain liver diseases such as primary biliary cirrhosis. It is a naturally occurring bile acid found in small quantities in normal human bile. It has not been studied in people with Huntington’s disease, and its use by your doctor would be “off label”.

Ursodiol is the oral form of a drug, part of which is converted to TUDCA by the human liver. TUDCA is the compound that has been shown to be beneficial in animal models of Huntington’s disease.

TUDCA interacts with mitochondrial membranes. It reduces cell damage by decreasing oxidative stress, glutamate injury, and decreasing activation of cell damage (apoptosis) factors.

Research studies have shown that TUDCA has been shown useful in the mouse model of Huntington’s disease, preventing brain atrophy, and improving neurological function even when given late in the disease (Keene, et al., PNAS, 2002). It has also been beneficial in protecting neurons from damage in acute neurologic injury of hemorrhagic stroke in the rat model (Rodriques et al., Journal of Cerebral Blood Flow & Metabolism 2001). There is a planned study in humans with ALS to start soon at the University of Minnesota.

The initial dosage will be 8-10mg/Kg/day given in 3 separate doses. This dosage will be increased every 2 weeks not to exceed 50mg/Kg/day.

Ursodiol is a very safe drug even at very high doses. It is so safe that there has never been a lethal level established.

Side effects include diarrhea, and abdominal distress and dyspepsia. It more rarely can cause rash, metallic taste, constipation, and gas. The dosage required for use in Huntington’s will likely cause more GI distress and diarrhea than smaller dosages. This adverse effect can be lessoned by gradual increase in dosage till GI tolerance is reached. We will encourage the use of anti diarrhea agents when this drug is used.

Keene, et al., Proceedings of the National Academy of Science; August 6, 2002 99 (16) 10671-10676.
Rodriques, et al., Journal of Cerebral Blood Flow & Metabolism; 22 (4) 463-471.