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Review

Disease Mechanisms and Therapeutic Approaches in SMARD1—Insights from Animal Models and Cell Models

Institute of Clinical Neurobiology, University Hospital Würzburg, Versbacher Strasse 5, 97078 Würzburg, Germany
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Author to whom correspondence should be addressed.
Biomedicines 2024, 12(4), 845; https://doi.org/10.3390/biomedicines12040845
Submission received: 22 February 2024 / Revised: 4 April 2024 / Accepted: 7 April 2024 / Published: 11 April 2024
(This article belongs to the Special Issue Molecular Insight into Human Diseases: Application of Animal Models)

Abstract

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal childhood motoneuron disease caused by mutations in the IGHMBP2 gene. It is characterized by muscle weakness, initially affecting the distal extremities due to the degeneration of spinal α-motoneurons, and respiratory distress, due to the paralysis of the diaphragm. Infantile forms with a severe course of the disease can be distinguished from juvenile forms with a milder course. Mutations in the IGHMBP2 gene have also been found in patients with peripheral neuropathy Charcot–Marie–Tooth type 2S (CMT2S). IGHMBP2 is an ATP-dependent 5′→3′ RNA helicase thought to be involved in translational mechanisms. In recent years, several animal models representing both SMARD1 forms and CMT2S have been generated to initially study disease mechanisms. Later, the models showed very well that both stem cell therapies and the delivery of the human IGHMBP2 cDNA by AAV9 approaches (AAV9-IGHMBP2) can lead to significant improvements in disease symptoms. Therefore, the SMARD1 animal models, in addition to the cellular models, provide an inexhaustible source for obtaining knowledge of disease mechanisms, disease progression at the cellular level, and deeper insights into the development of therapies against SMARD1.
Keywords: spinal muscular atrophy with respiratory distress type 1; SMARD1; motoneuron; muscle; helicase; IGHMBP2 spinal muscular atrophy with respiratory distress type 1; SMARD1; motoneuron; muscle; helicase; IGHMBP2
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MDPI and ACS Style

Jablonka, S.; Yildirim, E. Disease Mechanisms and Therapeutic Approaches in SMARD1—Insights from Animal Models and Cell Models. Biomedicines 2024, 12, 845. https://doi.org/10.3390/biomedicines12040845

AMA Style

Jablonka S, Yildirim E. Disease Mechanisms and Therapeutic Approaches in SMARD1—Insights from Animal Models and Cell Models. Biomedicines. 2024; 12(4):845. https://doi.org/10.3390/biomedicines12040845

Chicago/Turabian Style

Jablonka, Sibylle, and Ezgi Yildirim. 2024. "Disease Mechanisms and Therapeutic Approaches in SMARD1—Insights from Animal Models and Cell Models" Biomedicines 12, no. 4: 845. https://doi.org/10.3390/biomedicines12040845

APA Style

Jablonka, S., & Yildirim, E. (2024). Disease Mechanisms and Therapeutic Approaches in SMARD1—Insights from Animal Models and Cell Models. Biomedicines, 12(4), 845. https://doi.org/10.3390/biomedicines12040845

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