title: Can the therapeutic efficacy of tocotrienols in neurodegenerative familial dysautonomia patients be measured clinically?
abstract: Familial dysautonomia (FD) is an inherited, fatal, neurodegenerative disorder manifested by autonomic/hypertensive crises and cardiac instability. Patients produce little IKAP, the gene product of the affected mutated gene, and have low levels of monoamine oxidase A (MAO A), whose reduced presence appears to result in an increased accumulation of biogenic amines, which is a trigger for hypertensive crises. As ingestion of tocotrienols elevates IKAP and MAO A in FD patients, we examined their impact on the frequency of hypertensive crises and cardiac function. After 3 to 4 months of tocotrienol ingestion, approximately 80% of patients reported a significant (> or = 50%) decrease in the number of crises. In a smaller group of patients, a postexercise increase in heart rate and a decrease in the QT interval were observed in the majority of participants. Based on these findings, we hypothesize that tocotrienol therapy will improve the long-term clinical outlook and survival of individuals with FD.
authors.affiliation: Laboratory for Familial Dysautonomia Research, Fordham University, Bronx, NY 10458, USA. rubin@fordham.edu
authors.forename: Berish Y
authors.initials: BY
authors.lastname: Rubin
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Anderson
authors.forename: Levente
authors.initials: L
authors.lastname: Kapás
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D004402:Dysautonomia, Familial / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism; D024508:Tocotrienols / Q000494:pharmacology / Q000627:therapeutic use*; D035602:Transcriptional Elongation Factors; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; C114720:Elp1 protein, human; D024508:Tocotrienols; D035602:Transcriptional Elongation Factors; D008995:Monoamine Oxidase