Dr. Yurchenco (NJ, USA) and Dr. Rüegg (Basel, Switzerland) are collaborating with Santhera Pharmaceuticals to develop an emerging gene therapy approach to treat LAMA2-CMD
Patients with LAMA2-CMD have a mutation in the LAMA2 gene – a gene responsible for making a protein called laminin-211. In the body, muscle cells and muscle fibres are surrounded by a kind of web called the extra-cellular matrix. This extra-cellular matrix provides mechanical support and stability to the muscles, allowing them to bind to other proteins to grow and function normally. The muscle cells are normally attached to the extra-cellular matrix via the laminin-211 protein. In LAMA2-CMD patients however, due to the mutation in the LAMA2 gene, the laminin-211 protein is either defective or almost entirely absent. The muscle cells consequently cannot attach to the extra-cellular matrix very well. This poor attachment between the muscle and extra-cellular matrix leads to the muscle weakness and poor muscle growth that is associated with LAMA2-CMD.
To overcome this aspect of the disease, Dr. Yurchenco and Dr. Ruegg have built upon their years of research to demonstrate that two replacement linker proteins called αLNNd and mini-agrin can help laminin-211 function more normally in LAMA2-CMD patients. In LAMA2-CMD animal models, this approach led to the restoration of the connection between muscle fibres and the extra-cellular matrix, leading to the recovery of muscle force and size in addition to prolonged survival.
Now in collaboration with Santhera Pharmaceuticals, the researchers will continue to work closely with work closely with clinical experts and the patient community to establish the best way to bring this approach to clinical use.
Santhera Pharmaceuticals is a Swiss biotechnology company committed to developing therapies for neuromuscular diseases including LAMA2-CMD.