University of Manchester Innovation Factory Background
Very many genetic diseases affect mesodermal tissues such as skeletal and smooth muscle, cartilage, bone, joints and the endothelium lining of blood and lymphatic vessels. Many are rare and some so rare that indeed they are not studied at all and there is not even the hope of a therapy for affected children. Many are devastating conditions that dramatically affect many organs and compromise life quality and expectancy. All lack an efficacious therapy.
Among genetic diseases affecting skeletal muscle, Duchenne muscular dystrophy (DMD) is the most common, affecting 1/4,000 newborn males. It is caused by mutations in the dystrophin gene, located on X chromosome and characterized by progressive deterioration of skeletal and cardiac muscle, leading to a variable but progressive limitation of the patient’s mobility, including confinement to a wheelchair and heart and/or respiratory failure typically by 30 years of age. Despite numerous attempts such as oligonucleotides to correct the mutated mRNA and AAV delivering micro-dystrophins (shorter and partially functioning proteins) DMD is still incurable and does not yet have a therapy with long lasting/curative benefits.
Technology Overview
Spun-out from a leading laboratory in mesoderm diseases, MusculaCell aims to develop a range of treatments for DMD patients with various genotypic backgrounds. For this University of Manchester researchers have combined cell therapy with exon skipping to exploit the advantages of both and compensate their drawbacks. The researchers have compelling in vitro and in vivo evidence. While the commercial potential of cell therapies has always been limited due to the need to personalise the therapeutic intervention to avoid immune rejection of the treatment, the researchers can engineer multipotent cells, called mesoangioblasts,to become invisible to the immune system and thus “universal donor cells”. This will allow development of a single product with the same genetic disease background. With this approach MusculaCell aims to provide treatments to about 60% of DMD patients.
Benefits
Efficient engraftment of treated cells in muscles
Potentiation of treatment along multinucleated muscle fibres: most engrafted cells fuse with regenerating muscle fibres and correct also their neighbouring nuclei within the multinucleated muscle fibre
Development of a single cell therapy product for the treatment of whole populations with the same genetic defect (unlike autologous approaches)
Pre‑clinical evidence of long lasting effects
Applications
The nature of the approach is flexible and modular in addressing gene disruption in many mesoderm genetic diseases. It may be extended to other muscular dystrophies and to rare diseases of the connective tissue that are due to mutations in genes encoding for proteins of the extra-cellular matrix.
Opportunity
Having shown proof of principle of the approach in an autologous cell transplant context the researchers are currently working towards the proof of concept of the approach with this universal donor cell. Following this significant milestone, MusculaCell will seek investment to support the pre-clinical and clinical development of treatments.