To improve motor endurance in old mice

Sarcopenia is the primary cause of impaired motor performance in the elderly, also responsible for increased morbidity and mortality. The prevailing approach to improve such condition has been manipulation of the myostatin system resulting in increased muscle mass, moderate improved strength, but not increased endurance. 

A novel protein (FOX-115) has been created combining myostatin inhibition with LRP4/MusKativation (essential for NMJ formation/mantainance). Ten mg/kg of FOX115 were subcutaneously injected three times/wk  to 22 mo old mice.  The same treatment schedule was applied to other groups receiving  ramatercept or vehicle (controls). After 3wks training with treadmill all groups initiated treatment and underwent treadmill exercise. Mild prodding shocks were delivered in case of inactivity. Exhaustion was set as inactivity despite 10 shocks in one min. Grip strenght was similarly assessed. After 5wks treatment mice were sacrificed and muscles histologically examined.

At treatment end FOX-115 mice increased their muscle mass by 17% versus controls whereas ramatercept increased by 43%, a highly significant difference. After 3wks administration FOX-115 mice necessitated significantly (Wilcoxon paired test) less prodding stimuli compared to controls and ramatercept.  As of the end of the third wk control and ramatercept groups started decreasing the distance run which at study end was significantly shorter  (18.2%and 14.4% less, respectively) than at the beginning whereas FOX-115 groups showed an increase of 2.8% from baseline.  Grip strength was similarly enhanced by  FOX-115 and rematercept. Histology demonstrated a significantly lower number of central nuclei per muscle fiber in FOX-115.

The novel biological FOX-115 increased muscle strength and endurance in old mice in the treadmill. Histology showed no major effects on muscle fibers, but changes in the neuromuscular junction. The antimyostatin induced hypertrophy seen with rematercept was quenched by FOX-115. This protein may offer a treatment option for sarcopenia patients.