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June 11, 2018

Jefferson, Drexel researchers test gel to restore independent breathing after spinal cord injuries

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Stock_Carroll - Thomas Jefferson Hospital Thom Carroll/PhillyVoice

An entrance to a Thomas Jefferson University Hospital building on South 10th Street.

Promising lab results show that a hydrogel designed to restore independent, unassisted breathing in the aftermath of a serious spinal cord injury could potentially prove effective in human beings, according to researchers from Thomas Jefferson University and Drexel University.

In animal tests, scientists used a specially formulated hydrogel that delivers a neuro-stimulator to repair damaged proteins at the site of the injury. Their study, published Monday in The Journal of Neuroscience, focused specifically on how the hydrogel impacted the phrenic nerves, which control the diaphragm and the rhythmic inflation of the lungs.

“The hydrogel can deliver a neuron-stimulating agent that repairs a critical aspect of spinal cord damage, while avoiding systemic side effects of the agent,” said co-senior researcher Angelo Lepore, an associate professor in the Vickie and Jack Farber Institute for Neuroscience at Jefferson. “We looked specifically at the bundle of nerves that control breathing. Our preliminary work in animal models could lead to new treatments in the future for patients suffering from respiratory compromise, and may also apply to restoring other functions affected by the injury.”

Lepore, joined by Drexel collaborator Yinghui Zhong, examined the effectiveness of the gel in binding, releasing and limiting the associated risks of BDNF (brain-derived neurotrophic factor), which can cause side effects including muscle spasms and irregular chronic pain if not properly targeted in treatment.

“The gel has the property of being able to release a specific dose, over a controlled period of time, in a particular area, can be implanted in a safe manner, and is biocompatible so the body does not mount an immune response to it,” said co-first author Biswarup Ghosh, a research associate in Lepore’s laboratory.

By injecting the BDNF-infused gel only at the injury site, the side effects of broader circulation seen in clinical trials for ALS patients can be avoided, Lepore said.

In hydrogel tests on rat models, researchers saw a 60-70 percent improvement in breathing control as measured by diaphragm-muscle contractions. At the cellular level, they observed the desired protection and maintenance of the brain-to-spine-to-diaphragm connection, which is held together by the phrenic nerves. In the set of nerves that helps set the rhythmic control of inhalation, the study even documented regrowth of those nerves.

“Although there are yet other types of damage that can occur during spinal cord injury, it’s encouraging to see this gel improve two extremely-important mechanisms by which breathing control is lost,” Lepore said.

Future research will look to determine whether there is an ideal time and dosage to apply the hydrogel, including when treatment isn't immediately available after injury, and whether or not the gel may have applications to protect and regrow other types of nerves that could improve functionality.

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