Pre-clinical results on naproxcinod in models of muscular dystrophy

The data were presented by Nicox and the Center for Genetic Medicine Research,(1) a centre within the Children’s Research Institute, Children’s National Medical Center, in a poster session on April 22nd at the Muscular Dystrophy Association (MDA) Scientific Conference in Washington, DC.

The research study data were presented in a poster entitledLong-term treatment with naproxcinod significantly improves skeletal and cardiac disease phenotype in mdx mouse model of dystrophy (poster #175). In this study, the effects of naproxcinod were investigated on skeletal and cardiac muscle function in mdx mice. Three doses of naproxcinod (10, 21 and 41mg/kg) were given orally to four-week-old mdx mice (a reference model for Duchenne Muscular Dystrophy, DMD) for nine months and compared to 0.9mg/kg of prednisolone.

The results of the study suggest that naproxcinod may have potential as a safe therapeutic option for the treatment of muscular dystrophies. Naproxcinod treatment at 10 and 21mg/kg resulted in significant improvements in hind limb grip strength as well as an approximately 25-30% decrease in inflammation in fore and hind limbs measured by in vivo optical imaging.

Furthermore, there were significant improvements in heart function as evidenced by improved fraction shortening and ejection fraction, measured using echocardiography, along with improvements in systolic blood pressure. In addition, the long term detrimental effects of prednisolone typically seen in skeletal and heart function were not observed at the effective doses of naproxcinod.

Naproxcinod is a CINOD (Cyclooxygenase-Inhibiting Nitric Oxide-Donating) anti-inflammatory candidate originally developed by Nicox for the relief of the signs and symptoms of osteoarthritis. The results presented on April 22nd 2013 were from an exploratory research study sponsored by Nicox and conducted at the Center for Genetic Medicine Research.(1) The objective was to investigate the potential for the use of naproxcinod in Duchenne Muscular Dystrophy (DMD) as there is evidence that nitric oxide can play a critical role in the functioning of skeletal muscle.

The Nicox’s current strategy is to evaluate the opportunity to out-licence naproxcinod for the treatment of the signs and symptoms of osteoarthritis of the knee. Separately, the Company is also seeking specialised partners in the field of rare diseases who would be able to undertake and fund the potential development of naproxcinod in muscular dystrophy. This approach is aimed at maximising the opportunities to progress the development of naproxcinod in one of these indications.

Muscular dystrophies are a group of inherited diseases that cause muscle weakness and muscle loss. These diseases are due to defects in muscle proteins, leading to structure alteration and continuous damage of fibres during contraction. DMD is the most common and serious form of muscular dystrophy, with the onset of symptoms occurring in early childhood (usually between three and five years of age) and primarily affects boys.

This progressive condition worsens throughout childhood, with patients becoming wheelchair-bound between the ages of seven and thirteen. Most DMD patients die by the age of 20, most frequently as a direct result of respiratory/cardiac failure.

1. The Center for Genetic Medicine Research (GenMed) is a center within the Children’s Research Institute, at Children’s National Medical Center, in Washington DC. The Center is dedicated to translational research in muscular dystrophy.  Founded in 1999, GenMed serves as the Department of Integrative Systems Biology (ISB) at the George Washington University School of Medicine and Health Sciences.  The muscle disease research group is among the largest worldwide, and includes drug development, pre-clinical, and clinical research groups. GenMed has 50 faculty members and about 170 staff.