Stem Cell Therapy using synovial stem cells and lentivirus
Action Duchenne has joined forces with Imperial College scientists to test the possibility of recovering stem cells from boys with Duchenne and then using a lentivirus to introduce exon skipping antisense oligonucleotides.
Non-muscle derived stem cells from DMD patients should have a greater stem cell capacity than muscle-derived stem cells, which will have been exhausted by their attempts to contribute to muscle regeneration. Previous work performed by members of this consortium has identified the synovial membrane (the membrane that covers the joints) as a source of human stem cells that can regenerate skeletal muscle. These stem cells may be obtained from DMD patients when they are undergoing necessary orthopedic surgery for foot or spinal problems. We will verify that these cells do, in our hands, contribute to muscle regeneration in the mdx mouse (a model for DMD).
Antisense oligonuclotides (AON) designed to “skip” mutated dystrophin exons hold great promise for the treatment of DMD. However, these AON are not long-lasting and would require frequent re-administration. If we could introduce AON into a gene expression construct into stem cells that are capable of contributing efficiently to muscle regeneration, we should be able to achieve persistent exon skipping and dystrophin expression in skeletal muscle. We will test the ability of lentivirus, that can become incorporated into the chromosomes of stem cells, which are often non-dividing and difficult to transfect with other viruses, to carry the AON into stem cells and use these stem cells as a vehicle to carry the AON into muscle fibres and give rise to long-lasting dystrophin production. If successful, this strategy could be used instead, or together with, systemically-delivered AON to treat DMD.
Dr Jenny Morgan and Professor Francesco Muntoni Imperial College London
Jenny Morgans Blog
Jenny and her team soon to move to UCL are undertaking excting stem cell research in the UK click here to view Jenny's reports.