CYTE-I-HD: phase I dose finding and tolerability study of cysteamine (Cystagon) in Huntington's disease.
Cystamine, an inhibitor of transglutaminases, slows progression of Huntington's disease in the murine model by approximately 20%. Cysteamine, the dimer of cystamine, is an orphan drug approved for the treatment of nephropathic cystinosis and has a similar benefit in the murine model but with a narrower therapeutic window. In a single-center open-label study, we determined the maximum tolerable dose (MTD) and side effects of cysteamine in people with Huntington's disease. Cysteamine was started at a dose of 10 mg/kg per day, divided into four doses, and increased by 10 mg/kg per day weekly until the development of intolerable side effects or a maximum dose of 70 mg/kg per day. Of the 9 subjects, 1 had an MTD of 10 mg/kg per day, 1 had an MTD of 20 mg/kg per day, the maximum dose was 30 mg/kg per day for 2, 40 mg/kg per day for 2, and 50 mg/kg per day for 3. Dose-limiting side effects were motoric impairment in 5 and nausea in 4. The dose found tolerable by 8 of the subjects was 20 mg/kg per day. All had a noticeable hydrogen sulfide odor at doses of 40 mg/kg per day or higher. We conclude that, at a dose of 20 mg/kg per day, cysteamine was tolerable in people with Huntington's disease. Nausea and motoric impairment were the dose-limiting side effects.
Dubinsky
Richard
R
Department of Neurology, University of Kansas Medical Center, Kansas City, 66160, USA. rdubinsky@safetyresearch.com
Gray
Carolyn
C
D000328:Adult; D003543:Cysteamine / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D012720:Severity of Illness Index
D011837:Radiation-Protective Agents; D003543:Cysteamine