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

• Published in: Biomedicines 2024-04, Vol.12 (4), p.845
• Main Authors: Jablonka, Sibylle, Yildirim, Ezgi
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Atrophy; Cell culture; Cell division; Cell therapy; Charcot-Marie-Tooth disease; Children; Diaphragm; Disease; Diseases; DNA helicase; Genes; Genetic aspects; Genetic testing; Genotype & phenotype; Health aspects; helicase; IGHMBP2; Medical research; Medicine, Experimental; motoneuron; Motor neurons; muscle; Mutation; Neurophysiology; Paralysis; Peripheral neuropathy; Proteins; RNA; RNA helicase; SMARD1; Spinal muscular atrophy; spinal muscular atrophy with respiratory distress type 1; Stem cells; Transfer RNA; Transplantation; Yeast
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12040845

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal childhood motoneuron disease caused by mutations in the 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 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 cDNA by AAV9 approaches (AAV9- 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.