DFF project – Muscular Dystrophy
Controlled release of antisense PNA oligomers for Duchenne Muscular Dystrophy treatment
Objective
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, and is caused by gene mutations that abolish production of functional dystrophin muscle protein. DMD is a lethal disorder, and currently approved treatment is limited to glucocorticoids. A promising new treatment exploits specifically targeted RNA acting drugs that are able to partially restore the dystrophin protein and thus muscle function. In order to significantly improve this new approach we shall combine new derivatives of the RNA targeting agent PNA with a novel controlled drug release formulation, in order to obtain significantly longer lasting and more efficient treatment regimes. The experiments will be conducted using the mdx mouse model for DMD, and the results will be the first step towards clinical trials using such a new regime.
Dansk resume
Duchenne muskeldystrofi er den mest almindelige og alvorligste form for muskelsvind og skyldes en genfejl, der resulterer i nedsat eller manglende funktion af muskelproteinet dystrofin. Sygdommen er indtil nu udelukkende blevet symptombehandlet med binyrebarkhormon; men eksperimentel genetisk behandling, som kan reetablere dystrofin aktivitet og dermed muskel genopbygning, har vist sig uhyre lovende. Nærværende projekt vil med afsæt i disse fremskridt ved hjælp af en veletableret musemodel for Duchenne muskeldystrofi udvikle, undersøge og validere en ny strategi til depotadministration af det genterapeutiske lægemiddel, således at dette løbende frigives til organismen. Endvidere vil vi optimere lægemidlet i forhold til depot-administrationen. Disse prækliniske forsøg vil være første skridt mod klinisk afprøvning af en ny behandlingsmetode.
Participants
Peter E. Nielsen (PI) Department of Cellular and Molecular Medicine
Camilla Brolin Hjortkjær, Department of Cellular and Molecular Medicine
Thomas Krag, Neuromuscular Research Unit, Rigshospitalet