Diffuse intrinsic pontine glioma (DIPG) is a devastating and aggressive pediatric brain cancer primarily found in children between the ages of five and nine. And typically, these young patients die within a year of diagnosis, with little chance of survival.
Due to the location of the tumour, locked deep within the brainstem, it’s challenging to remove surgically, and cannot be cured by radiation therapy or chemotherapy. So the race is on to discover new treatment options that could change the game for these children.
Enter professor Adrian Krainer of Cold Spring Harbor Laboratory, renowned for his trailblazing work on antisense oligonucleotides (ASOs)—molecules with the power to regulate protein levels in cells. Krainer’s research led to the development of Spinraza®, the first FDA-approved therapy for spinal muscular atrophy (SMA), a deadly neurodegenerative disease.
With the success of Spinraza under his belt, Krainer turned his attention to other diseases where ASOs could be game-changers, and DIPG quickly emerged as a prime candidate. “I was approached by a neurologist and his friend who lost her child to DIPG,” Krainer recalls. “They wondered if our work on SMA could be applied. Every disease has its own challenges, but it seemed feasible. We believed it might be possible to create a therapy.”
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Fast forward to today, and Krainer, graduate student Qian Zhang, and their team have made significant progress in developing a potential therapeutic for DIPG using ASO technology akin to Spinraza. This novel treatment has shown promise in slowing tumour growth, reversing specific cancer cell changes, and extending survival rates in mice with DIPG. Krainer’s groundbreaking SMA research laid the groundwork for these advances.
“While working on Spinraza, we learned how to deliver ASOs to the spinal cord and brain,” Krainer explained. “They have lasting effects in those areas. We knew there was potential for treating other diseases.”
Diffuse intrinsic pontine glioma (DIPG) explained
Cancer is undoubtedly a tragedy, affecting millions of people worldwide. However, few people have ever heard of DIPG. And even fewer people are likely to understand its impact on the body.
The term “diffuse” refers to the way the tumour spreads throughout the brainstem, while “intrinsic” means that the tumour arises from within the brainstem, and “pontine” refers to the specific location of the tumour in the pons region of the brainstem.
Unfortunately, the causes of DIPG remain unknown, and there are no known risk factors or preventative measures for the disease. Symptoms of DIPG can include difficulty with coordination and balance, trouble speaking and swallowing, weakness or paralysis on one side of the body, headaches, and vision problems.
Currently, treatment options for DIPG are limited and primarily aimed at relieving symptoms and improving the quality of life for the patient. While radiation therapy can help shrink the tumour and alleviate symptoms temporarily, it almost always regrows. Clinical trials are underway to develop new treatments for DIPG, but progress has been slow due to the complexity of the disease and the challenges in studying it.
An innovative approach
Now that you have a better understanding of DIPG and how it works, here’s how Krainer and his team’s ASO drug intend to tackle this particular cancer.
The innovative ASO drug works by targeting a mutated protein called H3.3K27M. In DIPG, this prevalent mutation disrupts closely related proteins from regulating numerous genes, resulting in uncontrolled cell growth—cancer. When the researchers administered the ASO drug to mice with DIPG, the affected genes returned to normal. Tumour growth slowed, and the animals’ lifespans increased.
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“After treatment, the cancer appeared dramatically different,” Krainer observes. “We saw a significant reduction in proliferating cells, and the tumour cells were transforming into healthy nerve cells. This indicates that DIPG’s malignant changes can be reversed, at least to some degree.”
Despite the encouraging results, Krainer acknowledges that there is still a long road ahead before this new therapeutic can enter clinical trials. Furthermore, the potential drug would likely need to be combined with other treatments like radiation or immunotherapy.
“Of course, we hope this will make it to clinical studies,” Krainer notes, “but we’re not relying solely on one approach. We’re actively exploring ways to enhance its effectiveness even further.”