Journal Article

Safety and Efficacy of RNAi Therapy for Transthyretin Amyloidosis

Coelho, Teresa, Meyers, Rachel E, Hawkins, Philip N, Chiesa, Joseph, Fitzgerald, Kevin, Lozeron, Pierre, Butler, James S, Clausen, Valerie A, Alvarez, Rene, Adams, David, Gamba-Vitalo, Christina, Mant, Timothy, Tranter, Elizabeth, Perez, Javier, Geissler, Mary, Borland, Todd, Cehelsky, Jeffrey, Vaishnaw, Akshay K, Suhr, Ole B, Falzone, Rick, Chen, Qingmin, Nochur, Saraswathy V, Harrop, Jamie, Hutabarat, Renta M, Munisamy, Malathy, Gollob, Jared A, Bettencourt, Brian R, Warrington, Steve, Silva, Ana, Sehgal, Alfica, Sah, Dinah W.Y

2013

Overview

Transthyretin amyloidosis is largely caused by synthesis of mutant transthyretin in the liver and deposition of transthyretin in other organs. A therapeutic approach mediated by RNA interference resulted in reduced transthyretin levels in affected patients and in controls. Transthyretin amyloidosis is a life-threatening disorder caused by the deposition of hepatocyte-derived transthyretin amyloid in various tissues and organs. 1 , 2 Circulating transthyretin is derived from the liver 3 and can form amyloid deposits in peripheral nerves and in the gastrointestinal tract, heart, and kidneys. Transthyretin is also synthesized by the retina and choroid plexus, 4 , 5 which can lead to vitreal and leptomeningeal deposits. More than 100 genetic variants of the gene encoding transthyretin ( TTR ) are associated with autosomal dominant forms of the disease, known as familial amyloidotic polyneuropathy 6 – 8 and familial amyloidotic cardiomyopathy. 9 – 11 The most common mutation associated . . .

• Publisher: Massachusetts Medical Society
• Subject: Adolescent / Adult / Amyloid / Amyloid Neuropathies, Familial - genetics / Amyloid Neuropathies, Familial - therapy / Amyloidosis / Animals / Biological and medical sciences / Body weight / Cardiomyopathy / Clinical trials / Dose-Response Relationship, Drug / Family medical history / Female / Gene expression / General aspects / Humans / Lipids / Liposomes / Liver / Macaca fascicularis / Male / Medical sciences / Metabolic diseases / mRNA / Mutation / Nanocapsules / Nanoparticles / Nervous system / Other metabolic disorders / Peripheral nerves / Prealbumin - genetics / Prealbumin - metabolism / Proteins / RNA, Small Interfering - administration & dosage / RNA, Small Interfering - therapeutic use / RNA-mediated interference / siRNA / Thyroid gland / Transplants & implants / Transthyretin / Vitamin A / Young Adult