Abstract
Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder caused by insufficiency of functional survival motor neuron (SMN) protein. Several clinical trials have been conducted with the aim of upregulating the expression of the SMN protein in SMA patients. In order to evaluate the efficiency of these SMN-targeted approaches, it has become necessary to verify SMN protein levels in the cells of SMA patients. Accordingly, we have developed a method allowing the evaluation of the functional SMN protein with < 1.5 mL of peripheral blood using imaging flow cytometry. The expression of SMN protein in CD3+, CD19+, and CD33++ cells obtained from SMA patients, was significantly reduced compared with that in cells from control subjects. In spot analysis of CD33++ cells, the intensities of SMN spots were significantly reduced in SMA subjects, when compared with that in controls. Therefore, SMN spots implied the presence of functional SMN protein in the cell nucleus. To our knowledge, our results are the first to demonstrate the presence of functional SMN protein in freshly isolated peripheral blood cells. We anticipate that SMN spot analysis will become the primary endpoint assay for the evaluation and monitoring of therapeutic intervention, with SMN serving as a reliable biomarker of therapeutic efficacy in SMA patients.
Highlights
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the destruction of motor neurons in the anterior horn of the spinal cord
We have developed a method allowing the evaluation of the functional survival motor neuron (SMN) protein in peripheral blood nuclear cells (PBCs) using imaging flow cytometry
The expression of SMN protein in CD3+, CD19+, and CD33++ cells obtained from SMA patients, was significantly reduced compared with that in cells from control subjects
Summary
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the destruction of motor neurons in the anterior horn of the spinal cord. It is caused by deletion or mutation of survival motor neuron 1 (SMN1) encoding the SMN protein [1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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