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.


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.


RESULTS
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.


CONCLUSIONS
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.
Liu
C-S
CS
Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua, Taiwan.
Hsu
H-M
HM
Cheng
W-L
WL
Hsieh
M
M
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D000067699:Ataxin-3; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D020234:Gait Ataxia / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D000077213:Lamotrigine; D008214:Lymphocytes / Q000378:metabolism; D017827:Machado-Joseph Disease / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D010865:Pilot Projects; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D012097:Repressor Proteins; D013234:Stem Cells / Q000378:metabolism; D016896:Treatment Outcome; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014227:Triazines; C092341:ATXN3 protein, human; D000067699:Ataxin-3; D000077213:Lamotrigine