Gene silencing therapy for human neurodegenerative disease

• Autorzy: Cleveland D.W.
• Języki publikacji: EN

Abstrakty

EN

The genes whose mutation causes human neurodegenerative disease are widely expressed within neurons and non-neurons of the nervous system, producing damage not only within the most vulnerable neurons but also within their partner neurons, glia, and endothelia. Sustained gene silencing or altered pre-mRNA splicing broadly within neurons and non-neurons throughout the nervous system has been achieved using injection into the nervous system of clinically feasible “designer DNA drugs” known as antisense oligonucleotides (ASOs). Beginning with the founding example for inherited ALS caused by mutation in superoxide dismutase, single doses of this “designer DNA-based” drug approach have been shown to produce sustained, catalytic (RNase H-dependent) RNA degradation of a target gene, thereby producing slowing of disease progression of ALS in rodents or sustained partial disease reversal for Huntington’s-like disease from single dose injection. Therapy with ASO injection is now in trial for ALS, Huntington’s disease, and myotonic dystrophy. An additional trial using an ASO that corrects the splicing of the SMN2 gene has demonstrated efficacy in spinal muscular atrophy (SMA). A trial is anticipated to initiate in 2017 for the most frequent cause of both ALS and frontal temporal dementia. An extension of this approach is development of synthetic CRISPR RNAs to induce transient activation of Cas9 nuclease to cleave and permanently inactivate a selected target gene.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.18

Twórcy

autor

Cleveland D.W.

• Ludwig Institute, University of California at San Diego, La Jolla, USA