Neuregulin-1β is a member of the
neuregulin family of
growth factors and is critically important for normal development and functioning of the heart and brain. A recombinant version of neuregulin-1β,
cimaglermin alfa (also known as
glial growth factor 2 or
GGF2) is being investigated as a possible
therapy for
heart failure. Previous studies suggest that neuregulin-1β stimulation of skeletal muscle increases
glucose uptake and, specifically, sufficient doses of
cimaglermin alfa acutely produce
hypoglycemia in pigs. Since acute
hypoglycemia could be a safety concern,
blood glucose changes in the above pig study were further investigated. In addition, basal
glucose and
glucose disposal were investigated in mice. Finally, as part of standard clinical chemistry profiling in a single ascending-dose human safety study,
blood glucose levels were evaluated in patients with
heart failure after
cimaglermin alfa treatment. A single
intravenous injection of
cimaglermin alfa at doses of 0.8mg/kg and 2.6mg/kg in mice resulted in a transient reduction of
blood glucose concentrations of approximately 20% and 34%, respectively, at 2h after the treatment compared to pre-treatment levels. Similar results were observed in diabetic mice. Treatment with
cimaglermin alfa also increased
blood glucose disposal following oral challenge in mice. However, no significant alterations in
blood glucose concentrations were found in human
heart failure patients at 0.5 and 2h
after treatment with
cimaglermin alfa over an equivalent human dose range, based on body surface area. Taken together, these data indicate strong species differences in
blood glucose handling after
cimaglermin alfa treatment, and particularly do not indicate that this phenomenon should affect human subjects.