Stem cells derived from patients could lead to new treatments for congenital muscular dystrophies

Researchers at Queen Mary University of London and University College London have shown that using stem cells derived from patients could help find new treatments for a group of congenital muscular dystrophies.

The proof of concept study generated the first patient-derived induced pluripotent stem cell (iPSC) model for studying dystroglycanopathy - a group of congenital muscular dystrophies often associated with brain malformations.

Our ability to test potential drugs on people with one of these conditions has been hampered by the lack of appropriate human cell models. We are confident that this study overcomes that challenge.

It also seems to confirm the feasibility of using patient-derived models to validate and assess promising drug candidates that are identified from large-scale drug screens. In that way it will boost the drug development process."

Dr Yung-Yao Lin, Lead researcher, Queen Mary University of London

The team took skin cells from a patient with a gene mutation which causes a severe form of congenital muscular dystrophy and reprogrammed the cells to an embryonic cell-like state which meant they could become any cell in the body.

The result is known as a patient-derived induced pluripotent stem cell (iPSC) model. Dr Lin and his colleagues then used a genome-editing tool to correct the mutation.

In a paper published today in EMBO Reports, they announced that this restored the interaction of proteins with α-dystroglycan, an extracellular matrix receptor. This process is known as glycosylation and it is the disruption of that interaction that causes congenital muscular dystrophies.

Simultaneously, the team, which included researchers from University College London, used mouse muscle cells to screen nearly 32,000 compounds from a drug library to identify any that increased glycosylation of the relevant α-dystroglycan. The iPSC model confirmed that one compound (4BPPNit) was effective using the patient-derived model.

Dr Lin said: "The impact of the compound was limited but it did suggest that researchers can now use our patient-derived iPSC model to step up the search for more effective compounds that can be used in new treatments to slow or reverse the progress of these diseases."