CONGENITAL MUSCULAR DISTROHY ASSOCIATED TO LMNA

PROJECT: Terapias Avanzadas para el Tratamiento de las Laminopatías.

PI: Ignacio Pérez de Castro Insúa and Fernando de Miguel Pedrero.

PERIOD/AMOUNT: 2016-2018; 150.000€.

FUNDING AGENCY: Fundación Andrés Marcio, niños contra la Laminopatía.

PROJECT: Terapias avanzadas para el tratamiento de laminopatías: edición genómica y terapia celular con células progenitoras mesenquimales (PI16CIII/00017).

PI: Fernando de Miguel Pedrero.

PERIOD/AMOUNT: 2016-2018; 117.550€

FUNDING AGENCY: Ministerio de Economía y Competitividad, Proyectos de Investigación en Salud-ISCIII, Acción Estratégica en Salud Intramural 2016.

Congenital muscular distropy associated to LMNA (L-CMD) is a rare genetic disease that appear in infants and young patients, and is characterized by slow progressive muscle weakness and wasting, atrio-ventricular conduction block, and respiratory distress. It is caused by mutations in LMNA gene which encodes for A-type lamins (lamin A/C), proteins that are part of the nuclear lamina in eucariotic cells. L-CMD is a severe disease with no cure currently available.

The aim of this project is to advance in the knowledge of the mechanisms underlying the development and progression of L-CMD and to test new therapeutic approaches based on advanced therapies. We propose two main objectives:

(1) Using cells carrying mutations associated with L-CMD, to develop a proof-of-concept for the therapeutic efficacy of gene editing with CRISPR.

  

(2) To revert the pathologic phenotype in experimental models of the disease with mesenchymal stem cells (wild type or corrected).

In this project, we will also generate a mouse model for the conditional expression of LmnaR249W, one of the mutations causing L-CMD. This unique experimental model will be used to test the therapeutic potential of gene editing and cell based therapies