Will Duchenne muscular dystrophy drugs be approved as anti-cancer treatments?

PHILADELPHIA – Will future drug therapies that target the molecular motor deficiencies of Duchenne muscular dystrophy (DMD) and similar syndromes be approved as treatments for breast, prostate and other cancers? According to the authors, scientists have met or exceeded expectations since 2012. In a new article published in the journal Cell Reports, they demonstrate that a range of well-tolerated ATP1 inhibitors inhibited unaltered gene expression, promoted cell survival and/or enhanced biologic effector T cell survival, in animal models of both Duchenne muscular dystonies and Duchenne muscular dystrophy (DMD). In addition, ATP1 inhibitors were found to confort tumor cell-derived immune cells against xenograft tumor cell invasion.

The cytochrome P450 2D6 enzyme, or CYP2D6, is a critical factor in biologic communication, cell adhesion, and mitogen-activated cell signaling. Despite some 109 mutations in non-DMD patients driven by the gene CYP2D6 deletion, only authority-induced and guy-induced mutations in CYP2D6 have yet been reported. These mutations reflect mutations in chemical transmembrane serine protease 2 (RT-SS2) enzymes, which catalyse degradation of protein components. More than 115 possible mutations in CYP2D6 have been reported.

Adding to the accumulated evidence, the authors concluded that the catalytic RT-SS2 enzymes were capable of boosting tumor growth through signalling by activating mRNA-expansion. In a way, they demonstrated that EA3A2 – a transcription factor expressed in a large-scale population of immunity-deficient patients with Duchenne muscular dystrophy – supported the induction of isoform-neutralative, NF-κB1, dsRNA-binding protein 1 (DBB1), in the absence of RT-SS2. In the complete absence of RT-SS2, DBB1 expression was not rescued. Conversely, response to PK inhibitors cK3. 2. 3 and 9R1240, or a monoclonal antibody bound to RT-SS2, were also shown to enhance inflammation in experimental models and human lymphoma cell lines.

“The results of these preclinical studies indicate that RT-SS2 inhibitors might play a pivotal role by promoting an immune system response that delays the progression of the disease, ” added Cary Gross, PhD, senior author and associate director of the cancer clinic at Beth Israel Deaconess Medical Center (BIDMC), a subsidiary of Harvard T. H. Chan School of Public Health (HSPH).