Projects we fund

Overview

Professor Chris Jones and his team discovered faults in the gene ACVR1 to be present in DMG, and have been working to take specific drugs targeting ACVR1 to clinical trial. Although promising, they are likely to produce only modest benefits on their own, and the team have been looking to combine them with other drugs which may be more likely to produce a durable response in patients.

Recently, the team discovered a previously unknown link between the ACVR1 gene and cholesterol metabolism to be a possible Achilles heel in DMG. Treating these tumour cells with ACVR1 inhibitors as well as drugs which interfere with production or transport of cholesterol led to a greater effect than you would expect by adding the effects of them alone. These include commonly used anti-cholesterol drugs such as statins, which gives us the exciting potential for moving rapidly to the clinic. To achieve this, Professor Jones plans a research programme that will help unravel why DMG cells are dependent on cholesterol, and how inhibiting ACVR1 subsequently kills those cells. This will be done by cutting edge molecular analyses in disease models established from patient tumour samples. The project will also look at a large number of different ACVR1 and cholesterol inhibitors in a wide panel of these cells to pick the best combination, and test this in mouse DMG models.

What difference will this project make?

As cholesterol-targeting drugs such as statins are readily available and non-toxic, this project has the possibility of moving this treatment quickly to clinical trial, including in the UK, via the teams leadership role in the international CONNECT consortium. These tumours have been highlighted in multiple petitions to the UK Parliament as representing a major unmet need, and any new treatment has the potential to make a major impact for children with this terrible disease.