PharmaFox has invented a series of new proteins (biologicals) for the treatment of neuro-muscular diseases. The lead compound contains two pharmaceutically active moieties. When these components are engineered together into one compound they employ a new and unique mode of action. The PharmaFox lead compound has been extensively tested and compared with the frontrunner compound of the competition, a myostatin inhibitor. In these experiments, mice treated with the PharmaFox compound showed significantly better muscle endurance and strength. Based on these results a patent has been filed.
Muscles are the contractile tissue responsible for all movement in living organisms. Key elements of muscle function are strength, power and endurance. Any loss of muscle function is invariably harmful to a greater or lesser extent, however for daily activities muscle endurance plays an important role. Handling housework, shopping and preparing meals are instrumental activities of daily living and require a considerable amount of muscle endurance.
Thus, successful treatment of muscle impairment should address besides muscle strength also muscle endurance.
Muscle strength is the amount of force a muscle, or group of muscles, can exert upon maximal contraction, generally against an external load. It is expressed as the greatest
measurable force that can be exerted by a muscle or muscle group to overcome resistance during a single, maximum effort.
Muscle power is force developed quickly and combines strength and speed. It is the rate of performing work.
Muscle endurance is the ability of a muscle or group of muscles to sustain activity in a prolonged fashion or exert repeatedly
Improving functional activity is an important prerequisite for the successful treatment of muscle degenerative disorders, independently of their cause. To measure functional activity, Regulatory Agencies such as the Food and Drug Agency (FDA) and European Medicines Agency (EMA) often use the 6 -minute walking test as a basis for approval of a drug intended to treat diseases of the muscle. The 6-minute walk test is an easy to perform and practical test for the assessment of aerobic exercise capacity. For these patients, 6 minute walking is significant effort requiring a substantial amount of muscle endurance. The treadmill is an alternative model system mimicking the 6-minute walking test.
Loss of muscle function is an area of great interest for the pharma industry for which currently no satisfying treatment is available. Steroids have been suggested for the treatment of
sarcopenia, but side effects limit their use. Research has identified myostatin as a protein that inhibits muscle growth. Inhibition of myostatin causes muscle hypertrophy, making the
muscle much thicker. A well-known example of muscle growth in the absence myostatin is the Piedmont bull (see picture to the left).
These data have triggered the interest of Pharma Companies to target myostatin inhibition. Currently six myostatin inhibitors are being or have been tested in clinical trials: Ramatercept (Acceleron), Stamulumab (Wyeth), Bimagrumab (Novartis), Domagrozumab (Pfizer), BMS-986089 (Bristol-Myers-Squibb), Trevogrumab (Regeneron) and Landogrozumab (Eli Lilly). To date, results in clinical trials have been disappointing for these myostatin inhibitors. Wyeth discontinued the development of Stamulumab due to unsatisfactory clinical results. Acceleron`s clinical Phase 2 trial for Duchenne muscular dystrophy in Canada was discontinued and Novartis failed to meet the primary clinical end points in a Phase 2b/3-studie for the treatment of sporadic inclusion body myositis. The unsatisfactory results show that an alternative approach is needed for the treatment of neuromuscular disorders.