Linked Life Data

21474353

Source:http://linkedlifedata.com/resource/pubmed/id/21474353

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-6-7
pubmed:databankReference
pubmed:abstractText
Canavan disease (CD MIM#271900) is a rare autosomal recessive neurodegenerative disorder presenting in early infancy. The course of the disease is variable, but it is always fatal. CD is caused by mutations in the ASPA gene, which codes for the enzyme aspartoacylase (ASPA), which breaks down N-acetylaspartate (NAA) to acetate and aspartic acid. The lack of NAA-degrading enzyme activity leads to excess accumulation of NAA in the brain and deficiency of acetate, which is necessary for myelin lipid synthesis. Glyceryltriacetate (GTA) is a short-chain triglyceride with three acetate moieties on a glycerol backbone and has proven an effective acetate precursor. Intragastric administration of GTA to tremor mice results in greatly increased brain acetate levels, and improved motor functions. GTA given to infants with CD at a low dose (up to 0.25 g/kg/d) resulted in no improvement in their clinical status, but also no detectable toxicity. We present for the first time the safety profile of high dose GTA (4.5 g/kg/d) in 2 patients with CD. We treated 2 infants with CD at ages 8 months and 1 year with high dose GTA, for 4.5 and 6 months respectively. No significant side effects and no toxicity were observed. Although the treatment resulted in no motor improvement, it was well tolerated. The lack of clinical improvement might be explained mainly by the late onset of treatment, when significant brain damage was already present. Further larger studies of CD patients below age 3 months are required in order to test the long-term efficacy of this drug.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1096-7206
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
203-6
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A safety trial of high dose glyceryl triacetate for Canavan disease.
pubmed:affiliation
Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel. Reevals@szmc.org.il
pubmed:publicationType
Journal Article, Clinical Trial