Targeting ALK2 in diffuse midline gliomas

Fast Facts

• Official Title: ALK2/ACVR1 Kinase Inhibitors for DIPG therapy
• Lead Researcher: Dr Alex Bullock
• Where: University of Oxford
• When: September 2016 – August 2020
• Cost: £491,051 over a period of four years
• Research type: Paediatric, Diffuse Midline Glioma (formerly DIPG), High Grade, Academic

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What is it?

We’re excited to have partnered with the Structural Genomics Consortium (SGC), an international group of researchers using new technologies to drive the discovery of treatments for incurable diseases.

As one of few charities to collaborate with the SGC, we’re propelling the next generation of discoveries forward. We’re funding two research posts within the SGC, focusing specifically on the biology and proteins involved in the development of brain tumours.

The SGC have a long standing interest in the gene ACVR1, which is found to be mutated in around 25% of cases of diffuse midline glioma (previously known as DIPG). When ACVR1 is mutated, it causes over-activation of a protein known as ALK2, which leads to excessive cell division and tumour growth.

The SGC’s previous research has enabled them to target ALK2 as a therapeutic option for another disease. With our support, they are now designing and creating new drugs to block the actions of ALK2, with the ultimate goal of delivering a new treatment for diffuse midline gliomas.

Why is it important?

Currently there’s a lack of treatment options for diffuse midline gliomas (formerly known as DIPG) and prognosis for those diagnosed is poor. This research is making headway to change this.
Diffuse midline gliomas are highly aggressive brain tumours found at the base of the brain. They’re the second most common primary, high grade brain tumour in children. This tumour is difficult to treat as the tumour infiltrates healthy brain in a diffuse manner, and therefore makes it hard to determine where the tumour ends and healthy tissue begins. In addition, the location of the tumour in the brainstem also makes the complete removal of diffuse midline gliomas impossible.

Radiation therapy is the standard treatment. However, it’s not a cure and can only temporarily stabilise symptoms. Less than 1% of children diagnosed with a DIPG survive for longer than five years, so it’s of utmost importance to advance research in this tumour type.

Who will it help?

This research aims to help children diagnosed with a diffuse midline glioma and their families.

Milestones

• Achieved
• The research team have created and analysed over 170 types of drugs to block the actions of ALK2.
• They’ve identified a molecule, called M4K2009, that’s shown significant promise in blocking the activity of ALK2.

• Anticipated
• Over the upcoming months, the team will further test M4K2009 to ensure it’s a safe and effective drug.
• They will also continue to explore different compounds that could be made into effective drugs.