Dataset Information

Next-Generation SINE Compound KPT-8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD.

ABSTRACT: Duchenne muscular dystrophy (DMD) is a progressive, X-linked childhood neuromuscular disorder that results from loss-of-function mutations in the DYSTROPHIN gene. DMD patients exhibit muscle necrosis, cardiomyopathy, respiratory failure, and loss of ambulation. One of the major driving forces of DMD disease pathology is chronic inflammation. The current DMD standard of care is corticosteroids; however, there are serious side effects with long-term use, thus identifying novel anti-inflammatory and anti-fibrotic treatments for DMD is of high priority. We investigated the next-generation SINE compound, KPT-8602 (eltanexor) as an oral therapeutic to alleviate dystrophic symptoms. We performed pre-clinical evaluation of the effects of KPT-8602 in DMD zebrafish (sapje) and mouse (D2-mdx) models. KPT-8602 improved dystrophic skeletal muscle pathologies, muscle architecture and integrity, and overall outcomes in both animal models. KPT-8602 treatment ameliorated DMD pathology in D2-mdx mice, with increased locomotor behavior and improved muscle histology. KPT-8602 altered the immunological profile of the dystrophic mice, and reduced circulating osteopontin serum levels. These findings demonstrate KPT-8602 as an effective therapeutic in DMD through by promotion of an anti-inflammatory environment and overall improvement of DMD pathological outcomes.

SUBMITTER: English KG

PROVIDER: S-EPMC9598711 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Next-Generation SINE Compound KPT-8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD.

English Katherine G KG Reid Andrea L AL Samani Adrienne A Coulis Gerald J F GJF Villalta S Armando SA Walker Christopher J CJ Tamir Sharon S Alexander Matthew S MS

Biomedicines 20220926 10

Duchenne muscular dystrophy (DMD) is a progressive, X-linked childhood neuromuscular disorder that results from loss-of-function mutations in the DYSTROPHIN gene. DMD patients exhibit muscle necrosis, cardiomyopathy, respiratory failure, and loss of ambulation. One of the major driving forces of DMD disease pathology is chronic inflammation. The current DMD standard of care is corticosteroids; however, there are serious side effects with long-term use, thus identifying novel anti-inflammatory an ...[more]

PMID: 36289662

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Dataset Information

Next-Generation SINE Compound KPT-8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD.

Publications

Next-Generation SINE Compound KPT-8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD.

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