![]() ![]() Based on our data and its safety profile for use in humans, we have identified quercetin as a priority disease-targeting therapeutic lead for clinical evaluation for the treatment of DM1 and DM2. DM1 is a life-threatening chronic disease with symptoms in the neuromuscular, cardiac, and central nervous systems, and compared with most neuromuscular diseases, its clinical presentation is very variable 3, 4. Quercetin treatment selectively reduced toxic RNA levels and rescued MBNL dependent mis-splicing in DM1 and DM2 patient derived cell lines and in the HSA LR transgenic DM1 mouse model where rescue of myotonia was also observed. In this study, using our previously established HeLa DM1 repeat selective screening platform, we identified the natural product quercetin as a selective modulator of toxic RNA levels. There are currently no approved treatments that target the root cause of disease which is the production of the toxic expansion RNA molecules. Myotonia tends to be more prominent in DM1 compared to DM2. citation needed It slowly progresses to involve other muscle groups, including the heart. DM is typically inherited, following an autosomal. Mutation of CNBP gene causes type 2 (DM2). 4 One manifestation of facial weakness is drooping of the eyelid ( ptosis ). Mutation of the DMPK gene causes myotonic dystrophy type 1 (DM1). Transcription of the expanded alleles produces toxic gain-of-function RNA that sequester the MBNL family of alternative splicing regulators into ribonuclear foci, leading to pathogenic mis-splicing. DM1 usually begins in the muscles of the hands, feet, neck, or face. In the era of personalized medicine, and in view of forthcoming novel therapeutic perspectives of gene therapy supported in their efficacy by results of preclinical studies 15, CNS manifestations in DM1 should be always objectively quantified and monitored. Myotonic dystrophy is a multisystemic neuromuscular disease caused by either a CTG repeat expansion in DMPK (DM1) or a CCTG repeat expansion in CNBP (DM2). the idea that DM1 may represent a progeroid disease 14. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |