Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain cancer that often kills within a year of diagnosis. DIPG occurs in an area of the brainstem called the pons, which controls many of the body’s most vital functions such as breathing, blood pressure, and heart rate. Now, researchers at Cold Spring Harbor Laboratory report they have developed a potential therapeutic for DIPG using antisense oligonucleotide (ASO) technology that lowered tumor growth and increased survival rates in mice.
The findings are published in Science Translational Medicine in a paper titled, “Antisense oligonucleotide therapy for H3.3K27M diffuse midline glioma.”
Cold Spring Harbor Laboratory professor Adrian Krainer, PhD, one of the authors of the study, is best known for his research on ASOs. His efforts led to Spinraza®, the first FDA-approved treatment for spinal muscular atrophy (SMA).
Krainer started looking into other diseases where ASOs could make a difference and started to look into DIPG. “I was contacted by a neurologist and his friend, who had lost her child to DIPG,” Krainer explained. “They called to ask if what we did for SMA could be applied. Of course, every disease has its own barriers and obstacles, but it seemed doable. We thought it might be possible to develop a therapy.”
Krainer, graduate student Qian Zhang, and their colleagues developed a potential therapeutic for DIPG using ASO technology similar to that in Spinraza.
“While working on Spinraza, we learned how to deliver ASOs to the spinal cord and brain,” he said. “They have long-lasting effects there. So, we knew there was potential for treating other diseases.”
The new ASO drug works by shutting down a mutated protein called H3.3K27M. In DIPG, the dominant mutation blocks closely related proteins from turning many genes on and off.
“After treatment, the cancer looked very different,” said Krainer. “We could see a lot fewer proliferating cells, and the tumor cells were differentiating into healthy nerve cells. That tells us DIPG’s malignant changes are reversible to an extent.”
Krainer explained further studies are needed before they can begin clinical trials.
“Certainly, we would like this to make it to clinical studies,” he says, “but we didn’t put all our cards into one approach. We’re exploring ways to make this even more effective.”
Their research gives hope for improving survival rates and paves a way for future research working to treat the deadly cancer.