Dr. Ryan Duchatel from University of Newcastle, Australia, was awarded a 2023 ChadTough Defeat DIPG fellowship for his groundbreaking project, Integrating Systemic and Local Therapeutic Vulnerabilities to Improve the Treatment of Diffuse Midline Glioma, under the mentorship of Dr. Matt Dun. His research is dedicated to optimizing the use of paxalisib in treating DIPG, as part of the ongoing international clinical trial PNOC022. We recently caught up with Dr. Duchatel to gain insights into the progress and findings of his work.
Developing effective treatments for children with DIPG/DMG faces two significant challenges. The first is designing therapies that specifically target cancer cells while minimizing harmful side effects to the rest of the body. The second challenge is creating treatments that can successfully penetrate the brain’s protective barrier to reach the tumor. Traditional chemotherapy drugs can’t penetrate this barrier, so researchers hope to discover new treatments that work alongside standard radiotherapy to attach the unique characteristics of DIPG / DMG tumors.
Dr. Duchatel’s research focuses on a drug called paxalisib, which has been successful in passing through the blood-brain barrier (BBB). In the four years preceding the fellowship, Dr. Duchatel and his team had discovered that the pathways paxalisib targets are crucial for DIPG survival. However, it was difficult to see the full benefits of the drug in clinical settings due to various bodily responses that reduce its effectiveness. Dr. Duchatel’s laboratory identified these responses and found ways to counteract them, leading to stronger and longer lasting anti-DIPG effects.
Dr. Duchatel’s fellowship from the ChadTough Defeat DIPG Foundation has been instrumental in optimizing the use of paxalisib in combination with radiotherapy and the oral drug ONC201 in the ongoing international clinical trial, PNOC022. This support has enabled Dr. Duchatel to fine-tune these treatments while also developing strategies to manage the body’s feedback mechanisms, ultimately enhancing the effectiveness of the therapy.
“Research is constantly pushing the frontiers of knowledge, and it’s inspiring to think that the theory, the process, or the discovery you make today may determine how things happen tomorrow.” – Ryan Duchatel
FIRST YEAR FINDINGS:
- Reducing Blood Sugar Side Effects: Paxalisib can cause high blood sugar and insulin issues. To address this, the project is exploring ways to control blood sugar using treatments like metformin.
- Improving Treatment Success: The project aims to reduce brain inflammation and high blood sugar caused by the treatment, which could make paxalisib more effective.
- Testing New Treatment Combinations: Preclinical tests are being conducted on various treatment combinations to find the best strategies, which could later be used in clinical trials.
Progress:
In the first year, significant progress was made on the first and third goals, resulting in a research paper submitted to a leading medical journal. The paper discusses how combining paxalisib with metformin helped control blood sugar and extended the survival of mice with brain tumors. The research was also presented at an international conference, where it received positive feedback.
Next steps include exploring other methods to control blood sugar, such as using a ketogenic diet or a specific type of drug, in combination with paxalisib.
