DR Cysteamine for Huntington's Disease

Huntington's Disease (HD) is a rare hereditary condition caused by a defective gene. This gene makes an abnormal protein which leads to the degeneration of certain nerve cells in the brain. Adult-onset HD, the most common form of this disorder, usually appears in patients who are in their early 30s or 40s.

There are few treatment options for HD. Drugs are available to help minimize some of the symptoms such as the uncontrollable movements and mood swings associated with HD. In preclinical studies, cysteamine has shown potential to slow the progression of HD.1, 2, 3, 4

Human and Preclinical Studies

The use of cysteamine in HD was first published in 1986.1 In 2005, Dr. Pinto and colleagues reported that cysteamine was beneficial to HD transgenic mice.2 In early 2006, Drs. Dubinsky and Gray found that cysteamine at 20 mg/kg per day was tolerable in patients with HD.3

Dr. Borrell-Pages and colleagues reported their findings in 2006 regarding the mechanism of action of cysteamine, suggesting that cysteamine has a neuroprotective effect in HD mice because it increases the levels of BDNF4, a neuroprotective factor, in the brain. They also suggest that BDNF levels can be used as a biomarker of efficacy for cysteamine in HD.5 Biomarkers can be an important development issue when a therapy is used to prevent or slow clinical manifestation of a disorder.

Development Activities for DR Cysteamine for Huntington's Disease

Raptor has recently announced a collaboration with Centre Hospitalier Universitaire (CHU) d’Angers in France, to support a clinical study of DR Cysteamine in HD patients. Clinical researchers at CHU d’Angers, in collaboration with the Curie Institute, have designed a protocol to investigate this potential mechanism in HD patients, using BDNF as a biomarker of potential efficacy.

The planned Phase 2 study will be a two-year, multi-center clinical trial. Investigators will use the Unified Huntington's Disease Rating Scale or UHDRS as the primary endpoint, and will also measure BDNF levels as a secondary endpoint. Their study will be funded through a grant from the French government.

In 2008, Raptor received FDA orphan drug designation for cysteamine formulations, including DR Cysteamine, for the potential treatment of HD.


Learn more about Raptor’s other clinical programs::

References:

  1. 1. Shults C, Steardo L, Barone P, Mohr E, Juncos J, Serrati C, Fedio P, Tamminga CA, Chase TN. Huntington's Disease: effect of cysteamine, a somatostatin-depleting agent. Neurology. 1986 Aug;36(8):1099-102.
  2. Pinto JT, Van Raamsdonk JM, Leavitt BR, Hayden MR, Jeitner TM, Thaler HT, Krasnikov BF, Cooper AJ. Treatment of YAC128 mice and their wild-type littermates with cysteamine does not lead to its accumulation in plasma or brain: implications in the treatment of Huntington disease. Neurochem. 2005 Aug;94(4):1087-101.
  3. Dubinsky R, Gray C. CTYE-I-HD: phase I dose finding and tolerability study of cysteamine (Cystagon®) in Huntington’s disease. Mov Disord. 2006 April;21(4):530-3.
  4. Ferrer, I., E. Goutan, C. Marin, M.J. Rey, and T. Ribalta Brain-derived neurotrophic factor in Huntington disease Brain Research 2000 866:257-261
  5. Borrell-Pages M, Canals JM, Cordelieres FP, Parker JA, Pineda JR, Grange G, Bryson EA, Guillermier M, Hirsch E, Hantraye P, Cheetham ME, Neri C, Alberch J, Brouillet E, Saudou F, Humbert S. Cysteamine and cysteamine increase in brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase. J Clin Invest. 2006 May;116(5):1410-24.