Date: 2014-08-07
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of preclinical data in Science
Company: PTC Therapeutics (USA - NJ)
Product: RNA splicing modifiers of the SMN2 gene
Action mechanism:
Disease: spinal muscular atrophy (SMA)
Therapeutic area: Neuromuscular diseases - Rare diseases - Genetic diseases
Country:
Trial details:
Latest
news: * On August 7, 2014, PTC Therapeutics announced that the journal Science published results of a preclinical study demonstrating that treatment with orally available RNA splicing modifiers of the SMN2 gene starting early after birth is preventing deficits in mouse models of Spinal Muscular Atrophy (SMA). Scientists from Roche Pharma Research and Early Development (pRED), PTC Therapeutics, the SMA Foundation, the University of Southern California and Harvard University collaborated to demonstrate that continuous treatment of SMA mice with these compounds increased life span, normalized body weight and prevented both disease-related motor dysfunction and neuromuscular deficits in a mouse model of SMA. The study used chemical screening and optimization to identify orally available small molecules that selectively alter the splicing of the SMN2 pre-mRNA to produce stable full-length SMN protein. The SMN2 splicing modifiers described in the Science article penetrated into all mouse tissues tested including brain, spinal cord and muscle, and thus improved SMN2 RNA splicing to increase SMN protein production in these disease-relevant tissues. As a result of the SMN protein increase, the compounds prevented the progression of SMA in a severe mouse model. These compounds also corrected SMN2 RNA splicing and increased SMN protein levels in cell cultures obtained from SMA patients, including stem cell-derived motor neurons. A Phase I clinical program to assess safety and tolerability with investigational compounds was initiated in early 2014. \"SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy\". Nikolai A. et al. Science. Vol 345, n°6197 pp. 688-693.
