MicroRNA quantitative RT-PCR analysis of CMT1A Plasma

Objective: To determine if microRNA’s (miR) are elevated in the plasma of
individuals affected by the inherited peripheral neuropathy
Charcot-Marie-Tooth Disease, type 1A (CMT1A), miR profiling was employed
to compare control and CMT1A plasma. Methods: We undertook a screen of
CMT1A and control plasma samples to identify miRs that are elevated in
CMT1A using a pilot screen of plasma miR by next generation sequencing,
followed by validation of selected miRs by quantitative PCR, and
correlation with clinical data and protein biomarkers. Results: After an
initial pilot screen, a broader screen confirmed elevated levels of
several muscle-associated miRNAs (known as myomiRs) along with a set of
miRs that are highly expressed in Schwann cells of peripheral nerve.
Comparison to other candidate biomarkers for CMT1A (e.g. Neurofilament L,
NfL) measured on the same sample set shows a comparable elevation of
several miRs and ability to discriminate cases from controls. In addition,
the putative Schwann cell miRs correlate with a recently described TMPRSS5
biomarker that is also elevated in CMT1A plasma, and this protein is most
highly expressed in Schwann cells. Conclusions: These studies identify a
set of miRs that are candidate biomarkers for clinical trials in CMT1A.
Some of the miRs may reflect Schwann cell processes that underlie the
pathogenesis of the disease.