Development of gene therapy for hypophosphatasia

Abstract

Hypophosphatasia (HPP) is a disease caused by an inborn defect in the production of alkaline phosphatase that affects bones and teeth. The six types are perinatal lethal form, perinatal benign form, infantile form, childhood form, adulthood form and odontohypophosphatasia. Treatments have historically been limited but, in 2015, an enzyme replacement therapy known as Asfotase Alfa was approved. This has improved life expectancy and quality of life but drawbacks such as requires 3-6 injections per week for life, injection pain and swelling at injection sites remain. Professor Koichi Miyake and his team at the Department of Gene Therapy at Nippon Medical School (NMS), Japan, are working to improve treatments for HPP. The researchers are developing novel therapeutic agents to potentially treat HPP by only single injection, one of which is ARU-2801. The hope is that this will not only prolong the life of HPP patients and improve their symptoms, but also improve their quality of life and will also improve the symptoms of patients with disease types that currently cannot be treated with enzyme replacement therapy. Miyake and the team have evaluated the efficacy and safety of ARU-2801 using non-human primates (NHPs). In their studies, ARU-2801 was able to maintain tissue nonspecific alkaline phosphatase (TNALP) expression in NHPs and mice for a long period, with no side effects. In future clinical trials the effectiveness of ARU-2801 will need to be confirmed in patients.