In a paper published this month in Diabetes, researchers have shown that anti-insulin receptor monoclonal antibodies can improve glycaemia in a novel mouse model of human insulin receptoropathy.
Mutations of the insulin receptor can cause severe insulin resistance and early diabetes, usually resulting in death in childhood. To date there has been no way to bypass the blocking effect of such receptor mutations. Antibodies that bind and activate the insulin receptor in a different way to insulin are able to activate mutant receptors and restore glucose tolerance in animal models. However, the benefits of antibody activation of these receptors are reduced by down regulation of the receptors at the cell surface.
Further research is now being conducted by first author, Dr Gemma Brierley and Prof Ken Siddle at the IMS-MRL in collaboration with Prof Robert Semple at the University of Edinburgh to determine how to overcome the process by which antibody-activated receptors are removed from the cell surface thereby paving the way for forward progress of antibodies as a treatment for rare forms of diabetes.