Spinal Muscular Atrophy

Kolb, Stephen J.; Kissel, John T.

doi:10.1001/archneurol.2011.74

Cited by 242 publications

(198 citation statements)

References 32 publications

(21 reference statements)

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“…20 While the genetic etiology of the disease is well-established, the molecular role of SMN in the disease is largely unknown and is the topic of many reviews. [25][26][27][28][29][30][31][32][33][34] …”

Section: Cajal Bodies and Their Componentsmentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body.

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Section: Cajal Bodies and Their Componentsmentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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“…15, 16 Natural history studies in the SMA type 1 population demonstrated shortened lifespan, with 68% mortality within the first 2 years of life 9, 10. With the advent of standardized care guidelines,17 the mortality of SMA type 1 infants has been reduced at 2 years of age to 30%, with nearly half of these infants dependent upon noninvasive ventilation 18.…”

Section: Introductionmentioning

confidence: 99%

Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study

Kolb

Coffey

Yankey

et al. 2016

Ann Clin Transl Neurol

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ObjectiveThis study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).MethodsThis prospective, multi‐center natural history study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular biomarkers were assessed at baseline and subsequent visits.ResultsEnrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the SMA and control infant cohorts aligned well. Motor function as assessed by the Test for Infant Motor Performance Items (TIMPSI) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP‐INTEND) revealed significant differences between the SMA and control infants at baseline. Ulnar compound muscle action potential amplitude (CMAP) in SMA infants (1.4 ± 2.2 mV) was significantly reduced compared to controls (5.5 ± 2.0 mV). Electrical impedance myography (EIM) high‐frequency reactance slope (Ohms/MHz) was significantly higher in SMA infants than controls SMA infants had lower survival motor neuron (SMN) mRNA levels in blood than controls, and several serum protein analytes were altered between cohorts.InterpretationBy the time infants were recruited and presented for the baseline visit, SMA infants had reduced motor function compared to controls. Ulnar CMAP, EIM, blood SMN mRNA levels, and serum protein analytes were able to distinguish between cohorts at the enrollment visit.

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“…Such complexity may result from different residual levels of SMN in different systems as well as multiple cellular functions and interacting partners of SMN (Boyer, et al, 2010;Cauchi, 2010;Wu, et al, 2011). Nevertheless, restoration of SMN levels or function is certainly a primary therapeutic strategy for SMA treatment (Kolb & Kissel, 2011). For example, activation of SMN2 transcription and restoration of SMN2 splicing ameliorate symptoms of SMA mice and thus provide promise for future SMA treatment.…”

Section: How Does Smn Deficiency Cause Sma Pathogenesismentioning

confidence: 99%