LGMD2A
Financiado
Development of a strategy to treat limb girdle muscular dystrophy LGMD2A using...
Development of a strategy to treat limb girdle muscular dystrophy LGMD2A using combined cell and gene therapy strategies
In Duchenne muscular dystrophy, several mutations can be corrected by the exon-skipping technique on cells. In limb-girdle muscular dystrophy type 2A (LGMD2A), however, all the mutations described to date do not seem to be good ca...
In Duchenne muscular dystrophy, several mutations can be corrected by the exon-skipping technique on cells. In limb-girdle muscular dystrophy type 2A (LGMD2A), however, all the mutations described to date do not seem to be good candidates for the RNA correction technology. The recently identified c.1782+1072 G>C mutation in LGMD2A patients could be potentially repaired at RNA level. The principal aim of this project is to mask the effect of this mutation in stem cells from patients that can be derived to muscle and to test its therapeutic potential in a mouse model. This is the first step to be considered before planning a clinical trial in patients with this mutation. Our long term goal is to generate new advanced therapy protocols (gene and cell therapies) against LGMD2A, a muscular dystrophy that is specially prevailing in the population of the Basque region. To this end, we will pursue the following aims: 1. To develop a therapeutic approach for LGMD2A patients who carry c.1782+1072G>C mutation. 2. Isolation, optimization of the in vitro culture and genetic correction of CD133+ cells from patients with this mutation. 3. Analysis of the efficacy of this combined therapeutic approach in murine models in vivo. In order to accomplish aims 1 and 2, we will develop a descriptive study with fibroblasts (from skin) and CD133+ cells (from blood and muscle) from donors, in which we will determine the efficiency, yield and myogenic potential for subsequent testing in mice. To accomplish aim 3 we will perform a double blind experimental approach in mice (wild type versus C3KO/scid and mdx/scid mice), using CD133+ cells with the most myogenic potential (from aim 2) as an in vivo therapy to determine the correction effect in the human calpain 3. This work would contribute to the treatment of LGMD2A patients who carry c.1782+1072G>C mutation in calpain 3 and it could also be helpful for the treatment of other patients with similar type of mutations.
ver más
Línea de financiación: concedida
El organismo FP7 notifico la concesión del proyecto el día 2014-11-29
Presupuesto
El presupuesto total del proyecto asciende a
100K€
Líder del proyecto
ASOCIACION INSTITUTO BIODONOSTIA
Investigación y desarrollo experimental en ciencias sociales y humanidades asociacion
Perfil tecnológico
TRL
4-5
50K
Perfil tecnológico
TRL
4-5
50K