New Molecule for Treating Deadly Pediatric Brain Tumor

by Dr. Meenakshy Varier on  February 28, 2017 at 11:07 AM Health Watch
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Highlights
  • Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric tumor that kills every victim that it strikes.
  • Most of these tumors have a mutant protein known as histone H3K27M.
  • The new molecule detaches proteins, known as bromodomain proteins, from their binding to this mutant protein stopping the growth of the tumor cells.
A molecule that stops the growth of an aggressive pediatric brain tumor has been discovered.
New Molecule for Treating Deadly Pediatric Brain Tumor
New Molecule for Treating Deadly Pediatric Brain Tumor

The discovery has been made by a team of researchers from Northwestern University.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive tumor that is always fatal and primarily strikes children under 10 years old.

About 300 children under the age of 10 years old in the U.S. are diagnosed with DIPG and it accounts for 10% of all childhood central nervous system tumor. Radiation therapy only helps prolong survival rate.

These tumors arise from the glial tissue of the brain that support and protect the brain neurons. They develop in the lowest part of the brain known as pons that control important functions like breathing, blood pressure and heart rate.

"This tumor kills every single kid who gets DIPG within one year. No one survives," said the study's first author, Andrea Piunti, a postdoctoral fellow in Shilatifard's lab in biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine.

"To the best of our knowledge, this is the most effective molecule so far in treating this tumor," said senior author Ali Shilatifard, the Robert Francis Furchgott Professor of Biochemistry and Pediatrics and the chair of biochemistry and molecular genetics at Feinberg. "Every other therapy that has been tried so far has failed."

Mutation Pathway

Shilatifard's lab had previously identified the pathway via which this mutation causes cancer in studies with fruit flies.

Researchers believed that targeting this pathway would be a great way to thwart the tumor and pushed forward with their molecular studies.

In experiments conducted in mice, researchers delivered the drug through their abdomen and they had an increased survival of 20 days, which is a long time in the life of a mouse.

Now the team at Northwestern Medicine and Lurie Children's is working on delivering the drug to the brain stem to see if the effect will be more potent and effective.

Testing the Molecule

To test the molecule, scientists took tumor cell lines from a pediatric patient that was untreated and injected those cells into the brain stem of a mouse.

The human tumor was engrafted in the brain of the mouse and it was treated with the molecule while scientists monitored the tumor.

The molecule stopped the growth of the tumor cells and forced them to turn into other types of cells, known as differentiation, thereby halting its growth.

Around 80% of these tumors have a mutant protein known as histone H3K27M. The molecule detaches proteins, known as bromodomain proteins, from their binding to this protein.

While the molecule itself is not yet available commercially, a similar class of molecules, BET inhibitors, is being tested in clinical trials for pediatric leukemia and other types of tumors.

"This work could not have been done anywhere in the world except Northwestern Medicine, because of all the scientists and physicians who have been recruited here during the past five years and how they work together to link basic scientific research to the clinic," Shilatifard said. "This discovery is the perfect example of how we take basic science discoveries and translate them to cure diseases at Northwestern Medicine."

The study is published in Nature Medicine.

References

  1. Diffuse Intrinsic Pontine Glioma (DIPG) - (http://www.danafarberbostonchildrens.org/conditions/brain-tumor/diffuse-pontine-glioma.aspx)
  2. Ali Shilatifard et al. Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas. Nature Medicine; (2017) doi:10.1038/nm.4296


Source: Medindia

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