Calcification inhibition – development of pharmacological treatment of calcification of heart valves and blood vessels.
As our project is focused on calcification of the aortic valve and how to inhibit it, we have developed a new model to study this. Most work has been performed in cell cultures from human aortic valves, but to have a more complete model with valve tissue, we have developed and published a model with cultured whole pig valve leaflets: A Novel Ex Vivo Model of Aortic Valve Calcification. A Preliminary Report. Zabirnyk A, Perez MDM, Blasco M, Stensløkken KO, Ferrer MD, Salcedo C, Vaage J.Front Pharmacol. 2020 Dec 17;11:568764. doi: 10.3389/fphar.2020.568764. eCollection 2020.PMID: 33390945.
Our first patent for a drug to inhibit heart valve calcification is now under investigation.
Project lead: Jarle Vaage, Arsenii Zabirnyk and Kåre-Olav Stensløkken
Institution: University of Oslo
Partners: Oslo University Hospital, Norway; The Chemical Biology Platform at NCMM, Oslo, Norway; Computational chemistry lab, University of Bergen, Norway
Funding: EC FP7 Marie Sklodowska-Curie COFUND Program, University of Oslo, Norway; Norwegian Health Association
Duration: 3 years
What if you could replace heart valve surgery with a pill? Calinhib is searching for molecules that block heart valve calcification using cell biology and artificial intelligence (AI). Finding this molecule and developing it into a therapeutic drug could stop heart valve calcification as soon as it is detected.
Over 1000 Norwegians need to undergo heart valve surgery each year as a result of calcification. Including pre-op testing and follow-up medical care, the cost of these surgeries is estimated to exceed 300 million NOK and is only expected to increase as the population ages. Developing a drug that stops calcification would not only reduce these costs, but would provide a non-invasive treatment for patients who are poor surgical candidates due to age or comorbidities.
Calinhib has an advantage against other labs that are developing a pharmaceutical treatment for calcification: Calinhib is able to work with cells from patient heart valves. Because of their relationship with local hospitals, they can collect calcified heart valves after replacement surgery. The researchers treat the valves to isolate and culture the cells so they can test various candidate molecules and find ones that stop calcification. They have already found five good candidates.
In addition to working with human cells, the researchers at Calinhib are taking a unique approach to solving this problem by specifically targeting the calcification process itself rather than trying to identify and treat the whole lead-up to heart diseases. While prevention is often the best approach, it is very difficult to predict who will ultimately get calcification. Giving pre-treatment drugs to all patients is far too expensive and risky. Physicians will be able to wait until calcification is detected to give patients the drug that Calinhib is developing to slow or stop the calcification process.
This research is still in the early stage, but the researchers expect to validate their candidate molecules very soon. After that, there is still the long process of preclinical and clinical testing ahead. Success in this project means reducing costs and improving quality of life not just for people with heart valve calcification, but potentially also for others experiencing one of a range of calcification disorders for which there are currently no pharmacological treatments. Calinhib is looking for collaborators in drug development and machine learning to verify and optimize these molecules.