Reduced Akt activity alleviates inhibition of FoxO, a transcription factor that upregulates the expression of the muscular atrophy factor (atrogin-1/MAFbx), and the upregulation of muscle atrophy factor accelerates muscle atrophy (68)
Apitegromab: Phase 3 SAPPHIRE in SMA# The Phase 3 SAPPHIRE trial represents the most advanced clinical success for any myostatin-targeted therapy: 188 patients aged 2-21 with Type 2 or 3 SMA, all receiving background SMN-targeted treatment Primary endpoint met : Clinically meaningful improvement on HFMSE (Hammersmith Functional Motor Scale Expanded) versus placebo (p=0.0192), with a mean difference of 1.8 points Functional responders : 30.4% of apitegromab patients achieved 3 or more point HFMSE improvement versus 12.5% placebo Upper limb function : Consistent improvement measured by RULM (Revised Upper Limb Module) Published in The Lancet Neurology This is notable because it overcomes the historical "mass-function disconnect" that plagued earlier myostatin inhibitors -- apitegromab improved actual motor function, not just muscle mass
It also lowers the risk of major cardiovascular events such as stroke, heart attack, or death in adults with type 2 diabetes who also have heart disease, and lowers the risk of worsening kidney disease, kidney failure (end-stage kidney disease), and death due to cardiovascular disease in adults with type 2 diabetes who also have chronic kidney disease
Consequently, activation of these neurons reliably reduces intake while also inducing sickness behavior 53,58
.png.jpg)
