Lithium Treatment for Patients With Spinocerebellar Ataxia Type I

Summary

This study will evaluate the side effects and tolerability of the drug lithium in patients with spinocerebellar ataxia type I (SCA1) an inherited disorder caused by loss of nerve cells in parts of the brain. Symptoms include ataxia (difficulty walking) and loss of muscle coordination and strength. Recent studies suggest that lithium may be helpful in treating some SCA1 symptoms. People between 18 and 65 years of age with SCA1 who have only difficulty walking or who have difficulty walking as well as tremor, hand incoordination or speech problems, may be eligible for this study. Participation requires three hospital admissions at the NIH Clinical Center and one outpatient visit. Participants undergo the following tests and procedures: Admission 1 (2-6 weeks) * Medical history, physical examination, blood and urine tests, electrocardiogram. * Evaluation of SCA1 symptoms (balance, walking, dexterity, tremor, memory, mood and concentration). * Monitoring of liquid intake and output (urine) and weight changes. * Lithium treatment Start treatment and remain in hospital until the blood level of the drug is stabilized; continue treatment at home after hospital discharge. Admission 2 (2-4 days, 4 weeks after hospital discharge). * Repeat of some or all of the procedures done at the first admission. * Continue lithium in hospital and at home after discharge, with local physician checking laboratory values as needed. Admission 3 (2-4 days, 8 weeks after Admission 2). * Repeat of some or all of the procedures done at other admissions. * Stop lithium. Outpatient Visit (4 weeks after Admission 3) * Evaluation of SCA1 symptoms. * Blood and urine tests.

Timeline

Start

2008-05-18

Primary completion

2010-02-25

Completion

2010-02-25

Publications

• Background Allagui MS, Vincent C, El feki A, Gaubin Y, Croute F. Lithium toxicity and expression of stress-related genes or proteins in A549 cells. Biochim Biophys Acta. 2007 Jul;1773(7):1107-15. doi: 10.1016/j.bbamcr.2007.04.007. Epub 2007 Apr 21.
• Background Cummings CJ, Sun Y, Opal P, Antalffy B, Mestril R, Orr HT, Dillmann WH, Zoghbi HY. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum Mol Genet. 2001 Jul 1;10(14):1511-8. doi: 10.1093/hmg/10.14.1511.
• Background de Chiara C, Menon RP, Dal Piaz F, Calder L, Pastore A. Polyglutamine is not all: the functional role of the AXH domain in the ataxin-1 protein. J Mol Biol. 2005 Dec 9;354(4):883-93. doi: 10.1016/j.jmb.2005.09.083. Epub 2005 Oct 18.

Drugs

Indications