Our Partnership

We, MDUK and The Duchenne Research Fund are funding Dr Francesco Saverio Tedesco, University College London, for 'Towards a genomic integration-free, iPS cell- and human artificial chromosome based therapy for Duchenne muscular dystrophy'.

This project combines cell and gene therapy to aim to repair the stem cells of those with DMD. It is being tested on a mouse model and is being funded for four years, starting 2014

What Are iPS Cells?

Skin cells from boys with Duchenne muscular dystrophy will be genetically re-programmed to become a type of stem cell called an induced pluripotent stem (iPS) cell, which can develop into any cell or tissue. In this case the aim is for them to develop into healthy muscle cells.

The mutated dystrophin gene in the iPS cells will be repaired by inserting a human artificial chromosome (HAC) containing a functional copy of the dystrophin gene. The iPS cells are then developed in the lab into a type of cell which is known to develop into muscle cells. These cells will be injected into an mouse model of Duchenne muscular dystrophy.The aim is that these cells will repair the muscle damage in the mouse model.

These tests will allow researchers to discover how successful and safe this method is. Stem cell development has to be carefully monitored to stop the cells changing into the wrong type of cells.

The first year report for this project says:

Within the first seven months of this project we have taken skin cells from one individual affected by Duchenne muscular dystrophy and turned them into iPS cells. We did this using a technique that does not lead to mutations in our DNA, thus preventing transformation of the stem cells into cancerous cells. This allows us to generate cells with high levels of safety for future transplantation studies.

We also analysed the biological properties of a previously established Duchenne muscular dystrophy iPS cell line. We further corrected the genetic defect in this cell line using a vector able to reintroduce the correct dystrophin gene, which is lacking in people with Duchenne muscular dystrophy. We then differentiated these cells into muscle-making cells that have shown to be stable.

Our future work for the coming year will be:

  • to generate additional iPS cell lines from different Duchenne muscular dystrophy patients (having many stem cell lines from different individuals allows us to see how different patient stem cells behave when transplanted into a model of Duchenne muscular dystrophy and understand the overall efficiency of this approach)
  • to further characterise the new stem cell lines and differentiate them into muscle-making cells able to generate skeletal muscle (this will be a critical step to show that the stem cells we have made can become fully functional muscle)
  • to correct the cell lines by introducing a vector called Human Artificial Chromosome containing the entire dystrophin gene. Cells will be further analysed to check their stability and safety.

What About Clinical trials?

The work is at an early stage. But if successful it could be a move towards the day when a person wth DMD could be treated with their own repaired stem cells, rather than the cells of others, which can be rejected by the immune system.