Effect of serotonin modulation on dystrophin-deficient zebrafish

Author:

Spinazzola Janelle M.12,Lambert Matthias R.12ORCID,Gibbs Devin E.1,Conner James R.1,Krikorian Georgia L.1,Pareek Prithu1ORCID,Rago Carlo3,Kunkel Louis M.12456ORCID

Affiliation:

1. Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA

2. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA

3. DMD Therapeutics Inc., Seattle, Washington, USA

4. The Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts, USA

5. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA

6. The Manton Center for Orphan Disease Research at Boston Children's Hospital, Boston, Massachusetts, USA

Abstract

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutation of the dystrophin gene. Pharmacological therapies that function independently of dystrophin and complement strategies aimed at dystrophin restoration could significantly improve patient outcomes. Previous observations have suggested that serotonin pathway modulation ameliorates dystrophic pathology, and reapplication of serotonin modulators already used clinically would potentially hasten availability to DMD patients. In our study, we used dystrophin-deficient sapje and sapje-like zebrafish models of DMD for rapid and easy screening of several classes of serotonin pathway modulators as potential therapeutics. None of the candidate drugs tested significantly decreased the percentage of zebrafish exhibiting the dystrophic muscle phenotype in the short-term birefringence assay or lengthened the lifespan in the long-term survival assay. Although we did not identify an effective drug, we believe our data is of value to the DMD research community for future studies, and there is evidence that suggests serotonin modulation may still be a viable treatment strategy with further investigation. Given the widespread clinical use of selective serotonin reuptake inhibitors, tricyclic antidepressants, and reversible inhibitors of monoamine oxidase, their reapplication to DMD is an attractive strategy in the field's pursuit to identify pharmacological therapies to complement dystrophin restoration strategies.

Funder

Ryan s Quest of the Duchenne Alliance

Publisher

The Company of Biologists

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3