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J Neurol Neurosurg Psychiatry. 2011 Aug;82(8):850-2. doi: 10.1136/jnnp.2009.200253. Epub 2010 Jun 15.

Quantification of SMN protein in leucocytes from spinal muscular atrophy patients: effects of treatment with valproic acid.

Author information

1
Rudolf Magnus Institute of Neuroscience, Department of Neurology, University Medical Centre Utrecht, The Netherlands. s.piepers-2@umcutrecht.nl

Abstract

BACKGROUND:

Spinal muscular atrophy (SMA) is caused by the homozygous deletion of the survival motor neuron (SMN)1 gene. The nearly identical SMN2 gene produces small amounts of full-length mRNA and functional SMN protein, due to a point mutation in a critical splicing site. Increasing SMN protein production by histone deacetylase inhibiting drugs such as valproic acid (VPA) is an experimental treatment strategy for SMA.

OBJECTIVE:

To investigate whether an SMN-specific ELISA could detect changes in SMN protein expression in peripheral blood mononuclear cells (PBMCs) after treatment with VPA.

METHODS:

The authors developed a sensitive SMN-specific ELISA. Six patients with SMA types 2 and 3 participated in the study. Recombinant SMN calibration curves were used to calculate SMN protein levels in PBMCs before and after 4 months of VPA treatment.

RESULTS:

The SMN ELISA was able to detect small differences in SMN protein concentrations, and differences in SMN protein levels in Epstein-Barr virus immortalised lymphocyte cell lines from SMA type 1 and 2 patients, carriers and healthy individuals (p<0.05). The mean SMN protein level in PBMCs from SMA patients was 22% (SD 15%) of the value in a healthy control. VPA treatment resulted in significantly increased SMN protein levels in five out of six SMA patients compared with baseline values (p<0.05), but did not restore SMN levels to normal values.

CONCLUSIONS:

SMN protein quantification by this SMN ELISA is a useful additional tool for evaluating the effects of experimental treatment in SMA.

PMID:
20551479
DOI:
10.1136/jnnp.2009.200253
[Indexed for MEDLINE]

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