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: Berish Y Rubin, Sylvia L Anderson, Levente Kapás
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 10 Issue 4 Pg. 837-41 (Apr 2008) ISSN: 1523-0864 [Print] United States
• PMID: 18177231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Carrier Proteins
• Elp1 protein, human
• Tocotrienols
• Transcriptional Elongation Factors
• Monoamine Oxidase

Topics

• Carrier Proteins (metabolism)
• Dysautonomia, Familial (drug therapy, metabolism, physiopathology)
• Heart Rate (drug effects)
• Humans
• Monoamine Oxidase (metabolism)
• Tocotrienols (pharmacology, therapeutic use)
• Transcriptional Elongation Factors
• Treatment Outcome