Development of dual antigen (Myostatin and Activin A) displayed Lactic acid bacteria as an oral therapeutic for muscle wasting and muscular dystrophy


Non-Gene Targeting Therapies

Poster Number: 122


Hyun-Jun Kang, PhD, Daeeun Ki, Gyeong-jun Nam, Kyeong-Soo Hahm


1. BioLeaders, 2. BioLeaders, 3. BioLeaders, 4. BioLeaders

Muscle wasting is associated with various clinical conditions, including neuropathy, genetic disorders, cachexia syndrome and muscle disorders. Declines in muscle mass and functional capacity reduces the quality of life and increases the risk of morbidity and mortality. However, despite high interest and research, the development of therapeutic agents to prevent or reverse muscle wasting is still an unmet medical need. It is known that activation of myostatin/activin signal transduction is important for inducing accelerated muscle catabolism leading to muscle loss in multiple disease states. In addition, inhibition of myostatin/activin action improves insulin sensitivity, reduces excess fat, weakens systemic inflammation, accelerates fracture healing in disease models. In previous study, oral inoculations of myostatin displayed recombinant Lactobacillus casei into mice resulted in high levels of serum IgG and mucosal IgA, as demonstrated by ELISA. Interestingly, these antibodies exhibited potent inhibiting activities against muscle wasting in mdx mice. In this study, we have constructed a novel surface dual antigen (Myostatin and Activin A) display system for lactic acid bacteria using the poly-γ-glutamic acid synthetase A protein (PgsA) of Bacillus subtilis as an anchoring matrix to develop safer and more efficient treatment using mucosal immune system. It was confirmed that two antigens were stably expressed in L. casei by Western blot and FACS analysis. It is expected to be used as a therapeutic agent for various muscle-related diseases by orally administering lactic acid bacteria expressing myostatin and activin A as antigens.