Main partners in this randomized, double-blind, placebo-controlled study in men with type 2 diabetes were AstraZeneca, Moderna Inc., Karolinska Institutet, and Sahlgrenska Academy at the University of Gothenburg. The findings have been published in the scientific journal Nature Communications.
First author and corresponding author is Li-Ming Gan, a professor at the Department of Molecular and Clinical Medicine at the Institute of Medicine, Sahlgrenska Academy, and at AstraZeneca.
VEGF-A mRNA was delivered to the study participants in a saline solution and was administered by intradermal injection into forearm skin in single ascending doses. The trial met its primary objectives of describing safety and tolerability and secondary objectives of protein production and changes in local blood flow post-injection.
Increase in blood flow
The study showed that the VEGF-A protein, post-injection of mRNA, had increased. At each sampling time, mean VEGFA protein levels, across all mRNA-treated sites from patients across all cohorts, were higher than that of placebo up to the 24-26 hour time point in the study.
The bioactivity of the VEGF-A protein post-injection was also observed by an increase in blood flow at injection sites, up to seven days following a single injection, and the treatment was overall well tolerated.
AstraZeneca is now leading a Phase 2a study with patients receiving epicardial injections of VEGF-A mRNA during coronary artery bypass grafting surgery. The recent study was funded by AstraZeneca.
Important milestone
In a press release from the Nasdaq listed company Moderna, co-author Dr Kenneth Chien, a professor of Karolinska Institutet and scientific co-founder of Moderna, comment on the study in Nature Communication:
“I believe this an important milestone in the field of mRNA therapeutics as it starts to address any questions regarding the delivery of mRNA to human tissues, the duration and level of the protein that can be expressed and the ability of the technology to have a physiologic, measurable function over a prolonged period of time”.
“Based on these early data, this approach may provide benefit to patients where proper blood flow is compromised in areas such as heart disease and diabetes as well as for other vascular complications.”
Title: Intradermal Delivery of Modified mRNA Encoding VEGF-A is Well Tolerated and Transiently Enhances Basal Skin Blood Flow in Patients with Type 2 Diabetes