Prosensa pub­lish­es a sen­si­tive, repro­ducible and objec­tive method­ol­o­gy for dys­trophin analy­sis in patients with Duchenne mus­cu­lar dys­tro­phy

Leiden, The Netherlands, Sept. 24, 2014 (GLOBE NEWSWIRE) — Prosensa Holding N.V. (NASDAQ: RNA), the bio­phar­ma­ceu­ti­cal com­pa­ny focus­ing on RNA-mod­u­lat­ing ther­a­peu­tics for rare dis­eases with high unmet need, today announced that the results of its research into devel­op­ing an accu­rate and repro­ducible method for the mea­sure­ment of dys­trophin in patients with Duchenne mus­cu­lar dys­tro­phy (DMD) and Becker’s mus­cu­lar dys­tro­phy (BMD) have been pub­lished in the online peer reviewed jour­nal PLOS ONE (
The pub­li­ca­tion, by Chantal Beekman et al from Prosensa, describes the Company’s semi-auto­mat­ed image analy­sis method, which was shown to be objec­tive (oper­a­tor inde­pen­dent), repro­ducible (in mul­ti­ple sam­ples and exper­i­ments) and sen­si­tive for assess­ing dys­trophin lev­els by immuno­flu­o­res­cence in mus­cle biop­sies from BMD and DMD patients in nat­ur­al his­to­ry stud­ies or clin­i­cal stud­ies with com­pounds aim­ing to restore dys­trophin expres­sion.
This method has also been test­ed as part of an inter­na­tion­al con­sor­tium ini­tia­tive, the Biochemical Outcome Measures study group, which focus­es on the opti­miza­tion of dys­trophin assays.
DMD is char­ac­ter­ized by the absence or reduced lev­els of dys­trophin expres­sion on the inner sur­face of the sar­colem­mal mem­brane of mus­cle fibers. Clinical devel­op­ment of ther­a­peu­tic approach­es aim­ing to increase dys­trophin lev­els requires sen­si­tive and repro­ducible mea­sure­ment of dif­fer­ences in dys­trophin expres­sion in mus­cle biop­sies of treat­ed patients with DMD. This, how­ev­er, pos­es a tech­ni­cal chal­lenge due to donor vari­ance in the occur­rence of rever­tant fibers and low trace dys­trophin expres­sion through­out the mus­cle fibers in the DMD biop­sies.
As dys­trophin expres­sion is vari­able between mus­cle groups and even with­in the same mus­cle, demon­stra­tion of a phar­ma­co­dy­nam­ic effect requires com­par­i­son of two biop­sies pre- and post-treat­ment, tak­en from the same mus­cle, and sam­pled from areas of sim­i­lar dis­ease state. Furthermore, deter­min­ing inten­si­ty of indi­vid­ual fibers and its dis­tri­b­u­tion across the biop­sy yields a more infor­ma­tive and objec­tive mea­sure of dys­trophin expres­sion than count­ing fibers.
“This inno­v­a­tive method­ol­o­gy, which has been devel­oped by Prosensa, under­scores our sci­en­tif­ic com­mit­ment to under­stand­ing DMD and devel­op­ing treat­ments for this dev­as­tat­ing dis­ease. We are pleased to share these devel­op­ments with the sci­en­tif­ic com­mu­ni­ty as it should help sup­port the DMD research field by enabling enhanced clin­i­cal tri­al pro­to­cols with more objec­tive and rep­re­sen­ta­tive mea­sures of dys­trophin. While this method­ol­o­gy is an impor­tant step for­ward in under­stand­ing dys­trophin expres­sion, chal­lenges remain due to vari­abil­i­ty in the mus­cle. Clinical out­come mea­sures, such as the six-minute walk test (6MWT), con­tin­ue to be the opti­mal mea­sure­ment of a drug’s effi­ca­cy in DMD,” explained Dr. Giles Campion, Prosensa’s Chief Medical Officer and Senior Vice-President R&D.

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