Clinical and Molecular Features and Therapeutic Perspectives of Spinal Muscular Atrophy with Respiratory Distress Type 1

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2015 Jun 23

PMID 26095024

Citations 8

Authors

Fiammetta Vanoli

Paola Rinchetti

Francesca Porro

Valeria Parente

Stefania Corti

Affiliations

Soon will be listed here.

Abstract

Spinal muscular atrophy with respiratory distress (SMARD1) is an autosomal recessive neuromuscular disease caused by mutations in the IGHMBP2 gene, encoding the immunoglobulin μ-binding protein 2, leading to motor neuron degeneration. It is a rare and fatal disease with an early onset in infancy in the majority of the cases. The main clinical features are muscular atrophy and diaphragmatic palsy, which requires prompt and permanent supportive ventilation. The human disease is recapitulated in the neuromuscular degeneration (nmd) mouse. No effective treatment is available yet, but novel therapeutical approaches tested on the nmd mouse, such as the use of neurotrophic factors and stem cell therapy, have shown positive effects. Gene therapy demonstrated effectiveness in SMA, being now at the stage of clinical trial in patients and therefore representing a possible treatment for SMARD1 as well. The significant advancement in understanding of both SMARD1 clinical spectrum and molecular mechanisms makes ground for a rapid translation of pre-clinical therapeutic strategies in humans.

Citing Articles

Clinically relevant mouse models of severe spinal muscular atrophy with respiratory distress type 1.

Holbrook S, Hicks A, Martin P, Hines T, Castro H, Cox G Hum Mol Genet. 2024; 33(20):1800-1814.

PMID: 39128026 PMC: 11457999. DOI: 10.1093/hmg/ddae116.

Infantile Hypotonia: A Case of Spinal Muscular Atrophy With Respiratory Distress Type 1 Presenting As Infant Botulism.

Cardenas J, Cardenas J, Lee A, Brown M, Galan F, Scimeme J Cureus. 2021; 13(10):e19006.

PMID: 34824924 PMC: 8609979. DOI: 10.7759/cureus.19006.

Point-of-care lung and diaphragm ultrasound in a patient with spinal muscular atrophy with respiratory distress type 1.

Berti B, Buonsenso D, De Rose C, Ferrantini G, de Sanctis R, Forcina N J Ultrasound. 2021; 25(2):395-398.

PMID: 33847972 PMC: 9148350. DOI: 10.1007/s40477-021-00584-w.

Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1).

Perego M, Galli N, Nizzardo M, Govoni A, Taiana M, Bresolin N Cell Mol Life Sci. 2020; 77(17):3351-3367.

PMID: 32123965 PMC: 11104977. DOI: 10.1007/s00018-020-03492-0.

Distal Spinal Muscular Atrophy: An Overlooked Etiology of Weaning Failure in Children with Respiratory Insufficiency.

Zoham M, Eghbalkhah A, Kamrani K, Khosroshahi N, Yousefimanesh H, Eskandarizadeh Z J Pediatr Intensive Care. 2019; 7(3):159-162.

PMID: 31073488 PMC: 6260352. DOI: 10.1055/s-0037-1617434.

References

Donnelly E, Lamanna J, Boulis N . Stem cell therapy for the spinal cord. Stem Cell Res Ther. 2012; 3(4):24. PMC: 3580462. DOI: 10.1186/scrt115. View

Giannini A, Pinto A, Rossetti G, Prandi E, Tiziano D, Brahe C . Respiratory failure in infants due to spinal muscular atrophy with respiratory distress type 1. Intensive Care Med. 2006; 32(11):1851-5. DOI: 10.1007/s00134-006-0346-8. View

Ruiz R, Lin J, Forgie A, Foletti D, Shelton D, Rosenthal A . Treatment with trkC agonist antibodies delays disease progression in neuromuscular degeneration (nmd) mice. Hum Mol Genet. 2005; 14(13):1825-37. DOI: 10.1093/hmg/ddi189. View

Rudnik-Schoneborn S, Stolz P, Varon R, Grohmann K, Schachtele M, Ketelsen U . Long-term observations of patients with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1). Neuropediatrics. 2004; 35(3):174-82. DOI: 10.1055/s-2004-820994. View

Weiss S, Reynolds B, Vescovi A, Morshead C, Craig C, van der Kooy D . Is there a neural stem cell in the mammalian forebrain?. Trends Neurosci. 1996; 19(9):387-93. DOI: 10.1016/s0166-2236(96)10035-7. View

Grohmann K, Wienker T, Saar K, Rudnik-Schoneborn S, Stoltenburg-Didinger G, Rossi R . Diaphragmatic spinal muscular atrophy with respiratory distress is heterogeneous, and one form Is linked to chromosome 11q13-q21. Am J Hum Genet. 1999; 65(5):1459-62. PMC: 1288300. DOI: 10.1086/302636. View

Smith S, Neaves W, Teitelbaum S . Adult stem cell treatments for diseases?. Science. 2006; 313(5786):439. DOI: 10.1126/science.1129987. View

Grohmann K, Schuelke M, Diers A, Hoffmann K, Lucke B, Adams C . Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nat Genet. 2001; 29(1):75-7. DOI: 10.1038/ng703. View

Nicholson S, Witherden A, Hafezparast M, Martin J, Fisher E . Mice, the motor system, and human motor neuron pathology. Mamm Genome. 2000; 11(12):1041-52. DOI: 10.1007/s003350010205. View

10.

Maystadt I, Zarhrate M, Landrieu P, Boespflug-Tanguy O, Sukno S, Collignon P . Allelic heterogeneity of SMARD1 at the IGHMBP2 locus. Hum Mutat. 2004; 23(5):525-6. DOI: 10.1002/humu.9241. View

11.

Maddatu T, Garvey S, Schroeder D, Zhang W, Kim S, Nicholson A . Dilated cardiomyopathy in the nmd mouse: transgenic rescue and QTLs that improve cardiac function and survival. Hum Mol Genet. 2005; 14(21):3179-89. PMC: 1350304. DOI: 10.1093/hmg/ddi349. View

12.

Lim S, Bowler M, Lai T, Song H . The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1. Nucleic Acids Res. 2012; 40(21):11009-22. PMC: 3505976. DOI: 10.1093/nar/gks792. View

13.

de Planell-Saguer M, Schroeder D, Rodicio M, Cox G, Mourelatos Z . Biochemical and genetic evidence for a role of IGHMBP2 in the translational machinery. Hum Mol Genet. 2009; 18(12):2115-26. PMC: 2685751. DOI: 10.1093/hmg/ddp134. View

14.

Kaindl A, Guenther U, Rudnik-Schoneborn S, Varon R, Zerres K, Schuelke M . Spinal muscular atrophy with respiratory distress type 1 (SMARD1). J Child Neurol. 2008; 23(2):199-204. DOI: 10.1177/0883073807310989. View

15.

Blaschek A, Glaser D, Kuhn M, Schroeder A, Wimmer C, Heimkes B . Early infantile sensory-motor neuropathy with late onset respiratory distress. Neuromuscul Disord. 2013; 24(3):269-71. DOI: 10.1016/j.nmd.2013.11.013. View

16.

ELLIOTT J . Experimental models of amyotrophic lateral sclerosis. Neurobiol Dis. 1999; 6(5):310-20. DOI: 10.1006/nbdi.1999.0266. View

17.

Jaudzems K, Jia X, Yagi H, Zhulenkovs D, Graham B, Otting G . Structural basis for 5'-end-specific recognition of single-stranded DNA by the R3H domain from human Sμbp-2. J Mol Biol. 2012; 424(1-2):42-53. DOI: 10.1016/j.jmb.2012.09.010. View

18.

Robbins P, Ghivizzani S . Viral vectors for gene therapy. Pharmacol Ther. 1998; 80(1):35-47. View

19.

Corti S, Nizzardo M, Nardini M, Donadoni C, Salani S, Del Bo R . Motoneuron transplantation rescues the phenotype of SMARD1 (spinal muscular atrophy with respiratory distress type 1). J Neurosci. 2009; 29(38):11761-71. PMC: 6666655. DOI: 10.1523/JNEUROSCI.2734-09.2009. View

20.

Zanetta C, Riboldi G, Nizzardo M, Simone C, Faravelli I, Bresolin N . Molecular, genetic and stem cell-mediated therapeutic strategies for spinal muscular atrophy (SMA). J Cell Mol Med. 2014; 18(2):187-96. PMC: 3930406. DOI: 10.1111/jcmm.12224. View