Clinical and molecular events in patients with Machado-Joseph disease under lamotrigine therapy.

OBJECTIVE: Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 is an autosomal dominant spinocerebellar degeneration, for which there is no effective treatment. PATIENTS AND METHODS: This study involved the clinical response of lamotrigine (LTG) on six MJD patients with early truncal ataxia and the effect of LTG on the alteration of ataxin-3 expression in the transformed MJD lymphoblastoid cells. RESULT: LTG medication was found, on the basis of single leg standing test tandem gait index, to effectively improve gait balance, but did not prove to be effective in the withdrawal period. In Western blot analysis of ataxin-3 in MJD lymphoblastoid cells, extracellular application of LTG, while leaving the normal level of ataxin-3 intact, decreased the expression of mutant ataxin-3 in a dose-related manner.
CONCLUSION: Our results indicated that LTG may have significant benefits in relief of gait disturbance in MJD patients with early ataxia, and may be related to the decreased expression of mutant ataxin-3.