Chris M. Jay¹, Nick Levonyak², Gregory Nemunaitis^2,3, Phillip B. Maples¹ and John Nemunaitis^1,2,4,5

¹Gradalis, inc., ²Mary Crowley Cancer Research Centers, Dallas, TX, USA. ³MetroHealth Medical Center, Cleveland, OH, USA. ⁴Texas Oncology, PA, USA. ⁵Baylor Sammons Cancer Center, Dallas, TX, USA.

Abstract

Hereditary inclusion body myopathy type 2 (HIBM2) is a myopathy characterized by progressive muscle weakness with early adult onset. The disease is the result of a recessive mutation in the Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase gene (GNE), which results in reduced enzyme function and sialic acid levels. A majority of individuals with HIBM2 are from Iranian-Jewish or Japanese decent, but isolated cases have been identified world wide. This article reviews the diagnostic criteria for HIBM2. Current research with a highlight on the biology of the disease and the role of GNE in the sialic acid pathway are assessed. Finally, therapeutic investigations and animal models are discussed with a focus on future studies to better understand the pathology of Hereditary Inclusion Body Myopathy and move therapeutic agents towards clinical trials.