Development of a new microRNA-based heart failure drug

Efficacy, safety and toxicology screening for a new microRNA-based heart failure drug

The recognition of microRNAs as potential therapeutic targets marks the principal step towards new therapeutic concepts that we address in heart failure. In this project, the aim is to expedite an accurate transition of knowledge from bench to bedside and transformation of RNA therapeutics into a clinical reality. Maastricht University was the first to successfully employ chemically stabilised short oligonucleotides that allow the sustained knockdown of an endogenous microRNA in the adult mouse and porcine heart in vivo, leading to profound protective effects against the development of heart failure. Mirabilis Therapeutics BV, a Maastricht-based spinoff Biotech company aimed at advancing microRNA-targeting molecules towards clinical reality, has optimised the pharmacological and chemical properties of the RNA therapeutic drug and optimised its delivery and routes to the heart.

Heart failure is a serious clinical disorder that represents the primary cause of hospitalization and death worldwide. Cardiac hypertrophy is the principal risk factor for the development of heart failure and lethal arrhythmias. A complex web of interconnected signalling pathways and microRNAs has been implicated in hypertrophy. Recent data on the biological processes causing this disease mark the principal step towards new therapeutic concepts. By counteracting the amount and activity of single microRNAs in the heart, they demonstrated that it is possible to prevent, delay and even reverse heart failure in robust animal models of disease. RNA therapeutics has demonstrated encouraging safety/toxicology profiles and has advanced to FDA approval and clinical application several times.

Summary
Maastricht University and Mirabilis Therapeutics BV have teamed up to employ chemically stabilised short oligonucleotides that allow the sustained knockdown of an endogenous microRNA in the heart. To start a clinical trial extensive pharmacodynamic/pharmacokinetic studies need to be performed.
Technology Readiness Level (TRL)
4 - 5
Time period
2 years
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