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Finding new methods to treat Diffuse Midline Glioma

Fast facts

  • Official title: Understanding the role of PRC2 deregulation in diffuse midline glioma (DMG; aka DIPG): novel strategies to inhibit EZH2 function
  • Lead researcher: Dr Adrian Bracken
  • Where: Trinity College Dublin
  • When: March 2018 - February 2021
  • Cost: £109,263 over three years
  • Research type: Paediatric, DMG/DIPG (High Grade), Academic

Developing alternative methods to block the disruption of chromatin regulation to treat Diffuse Midline Glioma.

Dr Adrian Bracken and his research team at Trinity College Dublin aim to develop new methods to treat diffuse midline glioma, formerly known as Diffuse Intrinsic Pontine Glioma (DIPG)*.

Previous research has demonstrated that the regulation of chromatin is disrupted in various cancers. Chromatin regulation refers to the process of DNA being wrapped around special proteins called histones. The research team will be focusing on finding new ways to block the activity of a particular protein involved in chromatin deregulation.

Diffuse midline glioma are a group of highly aggressive brain tumours found in the middle of the brain stem (the pons). With this area being a difficult to access region of the brain, it is impossible to surgically remove the tumour using current technology.

The current treatment for this tumour type consists of radiation therapy; however, it is not a cure and only serves to stabilise symptoms temporarily.

Chromatin regulation refers to the process of DNA being wrapped around special proteins called histones. Previous research has demonstrated that the regulation of chromatin is disrupted in various cancers.

Blocking the activity of EZH2, a particular chromatin-associated protein, with a drug has shown promise in the treatment of cancers, including gliomas. However, researchers have discovered mutations, or changes, within EZH2 that make the drug ineffective.

Dr Bracken and his research team aim to develop alternative strategies to block the activity of EZH2 activity.

To accomplish this, the research team will test the ability of various other drugs to block the activity of EZH2. In addition, the researchers will test the effects of blocking other chromatin-associated proteins.

This research is addressing the acute need to find effective methods to treat diffuse midline glioma. Furthermore, it will also lay the foundation for subsequent clinical trials.

*Following the 2016 revision to WHO classification, this tumour is now known clinically as “Diffuse Midline Glioma- Pontine Location H3 K27M."

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