Ultra-Orphan drug development for GNE Myopathy: A synthetic literature review and meta-analysis.

GNE myopathy is an autosomal recessive hereditary muscle disorder that has the following clinical characteristics: develops in early adulthood, gradually progresses from the distal muscles, and is relatively sparing of quadriceps until the advanced stages of the disease. With further progression, patients become non-ambulatory and need a wheelchair. There is growing concern about extra-muscular presentations such as thrombocytopenia, respiratory dysfunction, and sleep apnea syndrome. Pathologically, rimmed vacuoles and tubulofilamentous inclusions are observed in affected muscles. The cause of the disease is thought to be a sialic acid deficiency due to mutations of the gene required for in vivo sialic acid biosynthesis. Sialic acid supplementation to a presymptomatic GNE myopathy mouse model was effective in preventing the development of the disease. Several clinical studies have been conducted to evaluate the safety and efficacy of sialic acid supplementation in humans. Based on the favorable results of these studies, an extended-release aceneuramic acid formulation was approved for treatment of GNE myopathy in Japan in March 2024. It is anticipated that it will be a significant step in the development of an effective treatment for GNE myopathy and other ultra-orphan diseases.