MTB-1, a selective gene regulator, for the treatment of Duchenne muscular dystrophy

George Mulligan, Mitobridge

1st April 2016

Mitobridge Inc. proposes the study of a new drug candidate, MTB-1, in a human clinical trial for the treatment of Duchenne muscular dystrophy (DMD). MTB-1 is a novel, potent and selective gene regulator that increases mitochondrial respiration and biogenesis. It is suggested that MTB-1 will activate multiple pathways linked to muscle health, which will lead to improved muscle endurance capacity.  
This proposal builds on various studies (Scholte and Busch, J Neurol Sci., 1980; Rybalka et al, PlosOne, 2014; Chen et al, JCB, 2000 and Baron et al, PlosOne, 2011, among others), which have demonstrated mitochondrial dysfunction in DMD patient tissues and cultured muscle cells as well as animal models, suggesting there are fundamental, intrinsic problems with mitochondria in dystrophic muscles. Thus, the mitochondria in DMD boys would be a good target for therapy with MTB-1, which aims to enhance mitochondrial function.

A range of pre-clinical data was presented, including tissue culture and in vivo studies using the dystrophic mdx mouse (which is a model of DMD).  The clinical proposal is general and at an early stage. The applicants sought advice from TACT regarding many aspects of the clinical trial that they propose would start in 2018.

The TACT panel felt that a clear advantage of the compound was its potential to have relevance for all DMD patients irrespective of ambulatory status and the underlying disease mutation. There was good pre-clinical evidence presented that the compound is highly specific and activates gene expression in model systems. In addition, TACT commended that the application’s functional studies were carried out in two separate laboratories.

TACT offered advice and recommendations including suggestions that could further support the pre-clinical hypothesis for MTB-1 and to help clarify the precise mechanism of action in DMD. In addition, the panel advised the applicant to seek regulatory guidance from the FDA and EMA early in the process and in advance of an investigational new drug (IND) application.

12 Apr 2017