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PERSPECTIVE article

Front. Vet. Sci.
Sec. Livestock Genomics
Volume 11 - 2024 | doi: 10.3389/fvets.2024.1415030
This article is part of the Research Topic Advances and Trends in Gene Expression, Regulation, and Phenotypic Variation in Livestock Science: A Comprehensive Review of Methods and Technologies View all 3 articles

Metabolic Gene Therapy in a Canine with Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease

Provisionally accepted
Michael Katz Michael Katz 1Dan G. Ohad Dan G. Ohad 2Philip Putter Philip Putter 3Nataly Shtraizant Nataly Shtraizant 4,5Ehud Shahar Ehud Shahar 6,7Smadar Tal Smadar Tal 2,8Efrat Eliyahu Efrat Eliyahu 1,9*
  • 1 Icahn School of Medicine at Mount Sinai, New York, United States
  • 2 Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, Jerusalem, Jerusalem, Israel
  • 3 Spot on Veterinary Hospital, Stamford, United States
  • 4 Frezent Biological Solutions, New York, United States
  • 5 SeneX Therapeutics, New York, United States
  • 6 Department of Plant Sciences, Migal - Galilee Research Institute, Kiryat Shmona, Israel
  • 7 Department of Biotechnology, Tel-Hai College, Upper Galilee, Israel
  • 8 Tel-Hai College, Tel Hai, Northern District, Israel
  • 9 Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States

The final, formatted version of the article will be published soon.

    Myxomatous mitral valve disease (MMVD) stands out as the most prevalent acquired canine heart disease. Its occurrence can reach up to 40% in small breed dogs and escalates in geriatric canine populations. MMVD leads to thickening and incomplete coaptation of valve leaflets during systole, resulting in secondary mitral valve regurgitation. Serious complications may arise concurrently with the worsening of mitral valve regurgitation, including left-and right-sided congestive heart failure, and pulmonary hypertension (PH). Ultimately, the PH progression might contribute to the patient's demise or to the owner's decision of euthanasia. Most currently available FDAapproved therapies for PH are costly and aim to address the imbalance between vasoconstriction and vasodilation to restore endothelial cell function. However, none of these medications impact the molecular dysfunction of cells or impede the advancement of pulmonary vascular and right ventricular remodeling. Recent evidence has showcased successful gene therapy approaches in laboratory animal models of PH. In this manuscript, we summarize the latest advancements in gene therapy for the treatment of PH in animals. The manuscript incorporates original data showcasing sample presentations, along with non-invasive hemodynamic assessments. Our findings demonstrate that the use of metabolic gene therapy, combining synthetic adeno-associated virus with acid ceramidase, has the potential to significantly reduce the need for drug treatment and improve spontaneously occurring PH in dogs.

    Keywords: Degenerative mitral valve disease, pulmonary hypertension, Gene Therapy, sphingolipids metabolism, Canine cardiovascular disease

    Received: 09 Apr 2024; Accepted: 10 Sep 2024.

    Copyright: © 2024 Katz, Ohad, Putter, Shtraizant, Shahar, Tal and Eliyahu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Efrat Eliyahu, Icahn School of Medicine at Mount Sinai, New York, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.