Cristina Quarta

C. Cristina Quarta, M.D ., Joel N. Buxbaum, M.D., Amil M. Shah, M.D., M.P.H., Rodney H. Falk, M.D., Brian Claggett, Ph.D., Dalane W. Kitzman, M.D., Thomas H. Mosley, Ph.D., Kenneth R. Butler, Ph.D., Eric Boerwinkle, Ph.D., and Scott D. Solomon, M.D.: The Amyloidogenic V122I Transthyretin Variant in Elderly Dark Americans Amyloid heart disease leads to a rise in ventricular wall stiffness and thickness of the heart.1 Abnormalities of transthyretin, a transport protein synthesized mainly by the liver, can lead to hereditary transthyretin-related amyloidosis.2 This disorder can be caused by any one of more than 100 stage mutations in the transthyretin gene ; the V122I variant, in which isoleucine is substituted for valine at placement 122, is the most typical mutation and happens in 3 to 4 percent of black Americans.3-5 V122I reduces the stability of transthyretin tetramers, causing cardiac deposition of misfolded transthyretin monomers and resulting in an autosomal dominant cardiomyopathy that typically occurs during or following the sixth decade of life, with a penetrance believed to be as high as 80 percent among men.6-9 The variant has been connected with increased risks of heart death and failure.

Importantly, the pattern of anticonvulsant efficacy of 2DG in screening models is distinctive as compared to currently available drugs. 2DG includes a well-established preclinical toxicity and efficacy profile, with decades useful as an imaging tracer, and also safety established during earlier Phase I/II individual clinical trials for cancers. Demonstration of efficacy in this preliminary clinical proof-of-principle trial would be a considerable milestone in the advancement of 2DG as a therapy for seizure disorders with the addition of evidence of efficacy and basic safety to current preclinical evidence in epilepsy animal versions.