Harnessing endogenous mechanisms to promote cardiac regeneration

The funding will enable the development of a first in class therapeutic for the repair of heart muscle based on modifying an endogenous molecule fully-reduced High Mobility Group Box 1 (FR-HMGB1).

It would only need to be administered once, within a few hours after myocardial infarction, to limit myocardial damage and promote cardiac regeneration in order to prevent the development of cardiac failure.

Our engineered molecule will retain the regenerative properties of FR-HMGB1 without the potential deleterious proinflammatory signalling mediated via RAGE (receptor for advanced glycation end-products), TLR-2 and TLR-4 (Toll-like receptors 2 and 4).

Following completion of the work described in this proposal, we will be well placed to proceed to GMP production and safety testing, in parallel with testing for efficacy in a pig MI model. We estimate that we will be ready to proceed to a phase 1 clinical trial within 4-years.

Our molecule will have the additional advantage that it could also be used for other areas of unmet medical need, including promoting fracture healing and recovery of neutrophil count following chemotherapy.