Grant Award 015

Project Summary: The long-term aim of this proposal is to develop a treatment for IBM2. The potential treatment is based on the autologous transplantation to the patients of their own myoblasts genetically corrected in culture, i.e., introduction of the normal GNE with a vector to complement the mutated GNE gene in the patient's own cells. My research group became interested in Hereditary Inclusion Body Myopathy (HIBM) following several e-mail messages from Dr. Daniel Darvish inquiring about our myoblast transplantation results. We have already produced retroviral and lentiviral vector containing the GNE gene. Some of these vectors contain markers to sort out genetically corrected cells. We will now test these vectors on myoblasts obtained from patients and from a knock-in mouse (HIBM mouse) made by Dr. Darvish. The genetically modified IBM2 myoblasts will be transplanted to IBM2 or SCID mice. This will permit us to verify whether the genetically corrected myoblasts can fuse with the existing mouse muscle fibers leading to the expression of the GNE enzyme. We will also verify whether this leads to the correction of the phenotype of the IBM2 mice. Although this grant proposal does not include the retransplantation of the genetically corrected myoblasts to the patients, this grant will permit to develop all the tools required to start such a clinical trial subsequently.