A New Treatment for Heritable Pulmonary Artery Hypertension Caused by Nonsense Mutations

Abstract

Heritable Pulmonary Arterial Hypertension (hPAH), caused by a nonsense mutation [premature termination codon (PTC)] in the BMPR2(Bone Morphogenetic Protein Receptor type II) gene, is a progressive fatal disease. We have identified Small Molecule Readthrough(SMRT) compounds that can readthrough PTCs in genes with nonsense mutations. Using specific genetic mouse models(Bmpr2 /R899X and Bmpr2 /R584X mice) of hPAH, we propose to test the efficacy of GJ103, our lead SMRT molecule in preventing hPAH and determine its efficacy in combination with nonsense mediated decay (NMD) suppression in preventing the hPAH development in our mouse models. We have genetic models in hand, approval to conduct the proposed work, which is going on. However, due to Covid 19-related severe restrictions and the complete shutting down of all non-essential animal studies from April 2020 to April 2021, progress on proposed aims was severely limited during the last year. On a positive note, however, with the gradual removal of the imposed restrictions, the animal work has re-started since last month, allowing us to be confident on making significant progress by the next reporting period.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2021
Accession Number
AD1145733

Entities

People

  • Virender Rehan

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Arteries
  • Biomedical Research
  • Blood
  • Blood Counts
  • Cardiovascular Diseases
  • Cardiovascular System
  • Catheterization
  • Covid-19
  • Diseases And Disorders
  • Health Services
  • Hypertension
  • Maryland
  • Medical Personnel
  • Molecules
  • Mutations
  • Peptide Growth Factors
  • Professional Development
  • Proteins
  • Pulmonary Hypertension
  • Standards

Fields of Study

  • Biology

Readers

  • Clinical Trial Research.
  • Microbial Pathology
  • Molecular Genetics

Technology Areas

  • Biotechnology