Molecules to Missiles
As hundreds of families each year can attest, diffuse intrinsic pontine glioma (DIPG) is a terrible diagnosis. A quick internet search for DIPG information paints the grim picture.
According to defeatdipg.org, a website created by an affected family to raise awareness and research funding, this brain tumor aggressively grows in a part of the brain stem called the pons. The pons controls essential bodily functions such as heartbeat, breathing, swallowing, eye movement, eyesight and balance. Because of the sensitive nature of its location, surgery is not an option to remove a tumor on the pons. Radiation has been shown to slow but not halt the tumor’s progression.
Children with DIPG commonly experience double vision, reduced eye movement, facial weakness or asymmetry, and arm and leg weakness. They also have problems with walking, coordination, speech, chewing and swallowing. Progressing on, it also interferes with breathing and heartbeat, which ultimately results in the child’s death.
“Virtually no one survives DIPG,” says Washington University School of Medicine neuro-oncology researcher Joshua Rubin, MD, PhD. “That’s what makes the new research funded by the CDI so exciting.”
The research Dr. Rubin refers to is an innovative study to explore the use of focused ultrasound to help penetrate the blood-brain barrier, which is otherwise meant to protect the brain from toxins. Yongjian Liu, PhD, radiology; and Hong Chen, PhD, biomedical engineering, have teamed up to develop this forward-thinking approach.
To take advantage of the tiny opening in the blood-brain barrier that Dr. Chen’s ultrasound technique creates, Dr. Liu is designing tiny nanoclusters made of copper small enough to fit through the opening. Inside those nanoclusters are chemotherapy drugs. Once the drug-infused nanoclusters enter the tumor, they dissolve, and the drugs are successfully deployed. Dr. Chen and Dr. Liu are testing this novel approach in collaboration with Dr. Rubin using brain tumor models based in mice.
Through PET imaging modeling technologies developed by Dr. Liu’s colleague, Yuan-Chuan Tai, PhD, in Washington University’s Mallinckrodt Institute of Radiology, the nanostructures can be tracked to ensure they are hitting their targets.
Nanomedicine, the science of turning molecules into missiles, has shown great potential in cancer diagnosis and therapy. However, the blood-brain barrier has limited its application.
“Focused ultrasound is an effective technique for noninvasive and localized blood-brain barrier opening,” says Dr. Chen. “The integration of nanomedicine and focused ultrasound provides a therapeutic platform for the treatment of not only DIPG, but other types of pediatric brain disease.”