Animal experiment:

Mice: Compounds (RG7800) are administered orally once daily (qd) for 10 days at three different doses (1, 3, and 10 mg/kg). One hour after the final dose, tissues are collected from the mice, and the level of the SMN protein is determined in the brain and quadriceps muscle[1].

RG7800 a small molecule SMN2 splicing modifier to enter human clinical trials to treat spinal muscular atrophy.

RG7800 increases the SMN protein level via induction of alternative splicing of the SMN2 mRNA. RG7800 is shown to promote the inclusion of exon 7 in SMN2 mRNA, generating full-length mRNA in vitro using fibroblasts from an SMA type I patient[1].

RG7800 shows favorable drug metabolism and pharmacokinetic profile in the rat and in cynomolgus monkey with good oral bioavailability. In SMA mouse model, treatment of RG7800 shows a clear dose dependent increase in SMN protein levels. Mice treated with RG7800 demonstrate a dose dependent increase in survival beginning at the low dose (0.3/1 mg/kg). In the middle and high dose groups (1/3 and 3/10 mg/kg, respectively), approximately 80-90% survive beyond PND50/PND60 with profound body weight gain when the study is terminated. RG7800 dose-dependently corrects SMN2 splicing by including exon 7 to create FL mRNA, suggesting that RG7800 corrects alternative splicing of the human SMN2 gene in the brain of transgenic SMA model mice, leading to an increase of the SMN protein in the brain[1].

References:
[1]. Ratni H, et al. Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy. J Med Chem. 2016 Jul 14;59(13):6086-100.