Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease.
Our group has previously reported the first clinical application of lithium in a child affected by Canavan disease. In this study, we aimed to assess the effects of lithium on N-acetyl aspartate (NAA) as well as other end points in a larger cohort. Six patients with clinical, laboratory and genetic confirmation of Canavan disease were recruited and underwent treatment with lithium. The battery of safety and efficacy testing performed before and after sixty days of treatment included Gross Motor Function Testing (GMFM), Magnetic Resonance Imaging (MRI) Proton Magnetic Spectroscopy (H-MRS) as well as blood work. The medication was safe without any clinical or laboratory evidence for toxicity. Parental reports indicated improvement in alertness and social interactions. GMFM did not show statistically significant improvement in motor development. H-MRS documented an overall drop in NAA which was statistically significant in the basal ganglia. T1 measurements recorded on MRI studies suggested a mild improvement in myelination in the frontal white matter after treatment. Diffusion Tensor Imaging was available in two patients and suggested micro-structural improvement in the corpus callosum. The results suggest that lithium administration may be beneficial in patients with Canavan disease.
Assadi
Mitra
M
Robert Wood Johnson Medical School, Neurology, 3 Cooper Plaza, Suite 320, Camden, NJ 08103, USA. assadi-mitra@cooperhealth.edu
Janson
Christopher
C
Wang
Dah-Jyuu
DJ
Goldfarb
Olga
O
Suri
Neeti
N
Bilaniuk
Larissa
L
Leone
Paola
P
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D017825:Canavan Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D002951:Citrates / Q000494:pharmacology* / Q000627:therapeutic use; D003401:Creatine / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D012720:Severity of Illness Index
D002951:Citrates; D001224:Aspartic Acid; D007294:Inositol; C070669:lithium citrate; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline