Nucleic acid therapy for transthyretin-type amyloidosis

Yoshiki Sekijima¹⁾²⁾

¹⁾Department of Medicine（Neurology and Rheumatology）, Shinshu University School of Medicine
²⁾Institute for Biomedical Sciences, Shinshu University

Transthyretin （ATTR） amyloidosis is a life-threatening, gain-of-toxic-function disease characterised by extracellular deposition of amyloid fibrils composed of transthyretin （TTR）.　TTR protein destabilised by TTR gene mutation results in autosomal dominant hereditary ATTR （ATTRv） amyloidosis.　Analogous misfolding of wild-type TTR results in wild-type ATTR （ATTRwt） amyloidosis, characterised by acquired amyloid disease in the elderly.　Clinical efficacy of liver transplantation and TTR tetramer stabilizers were established for both ATTR amyloidosis.　Recently, the clinical effects of small interfering RNA （patisiran） and antisense oligonucleotides （inotersen） for suppression of both variant and wild-type TTR synthesis were demonstrated in randomised clinical trials.　With the development of effective disease modifying therapies, early and precise diagnosis is essential to improve patients' prognosis.

Address correspondence to Dr. Yoshiki Sekijima, Department of Medicine （Neurology and Rheumatology）, Shinshu University School of Medicine （3-1-1 Asahi, Matsumoto 390-8621, Japan）