Northwestern University researchers have developed a peptide-based treatment that can significantly reduce long-term brain damage after a stroke, a major cause of long-term disability. Published today in the journal Neurotherapeutics, their study showed that the experimental therapy could be delivered intravenously and cross the blood-brain barrier without the need for surgery or invasive injections directly into the brain.
Stroke treatment currently focuses on restoring blood flow to the affected area of the brain as soon as possible, typically removing the blood clot through medication or surgery. However, the sudden return of blood flow can have long-term consequences for patients, who often experience cognitive decline in the year following a severe stroke.
“Current clinical approaches are entirely focused on blood flow restoration,” said Ayush Batra, MD, associate professor of neurology and pathology at Northwestern University’s Feinberg School of Medicine and a neurocritical care physician at Northwestern Medicine. “Any treatment that facilitates neuronal recovery and minimizes injury would be very powerful, but that holy grail doesn’t yet exist. This study is promising because it’s leading us down a pathway to develop therapeutics for this unmet need.”
The experimental therapy is based on supramolecular therapeutic peptides (STPs), a technology developed at Northwestern also known as ‘dancing molecules’ due to their dynamic nature. A previous study had shown that a single injection of STPs could reverse paralysis and repair damaged tissue in a mouse model of spinal cord injury. Immediately after injection, the STPs formed a gel that matches the structure of the extracellular matrix found in the spinal cord, mimics the motion of biological molecules and incorporates active agents that encourage neurons to self repair and regrowing axons to restore lost communication.
“One of the most promising aspects of this study is that we were able to show this therapeutic technology, which has shown incredible promise in spinal cord injury, can now begin to be applied in a stroke model and that it can be delivered systemically,” said Samuel I. Stupp, PhD, professor at Northwestern’s McCormick School of Engineering and founding director of the Center for Regenerative Nanomedicine. “This systemic delivery mechanism and the ability to cross the blood-brain barrier is a significant advance that could also be useful in treating traumatic brain injuries and neurodegenerative diseases such as ALS.”
In the current study, the STPs were tested in a mouse model of acute ischemic stroke, which accounts for 80% of all stroke cases in the U.S. A lower concentration was used in this case to prevent clotting as the peptide therapy enters the bloodstream. The small size of the peptides allows them to cross the blood-brain barrier and form larger nanofiber networks within the brain once enough of the molecules have passed through.
Results showed that the STPs significantly reduced brain damage following a stroke, as well as mitigating excessive inflammation and immune responses. Mice were followed for seven days, during which the treatment showed no signs of toxicity or other side effects.
Stupp explained that after a clot is removed, all harmful molecules accumulated during the blockage get released at once into the bloodstream: “The dancing molecules carry with them some anti-inflammatory activity to counteract these effects and at the same time help repair neural networks.”
Going forward, the team plans to study longer-term effects of this treatment on stroke recovery, as well as testing the addition of molecules that can signal neurons to regenerate to further improve results. With the ultimate goal of eventually translating this research into a therapy that can complement existing stroke treatments, curbing secondary brain injuries. Batra added: “Reducing this level of disability with a therapy that could potentially help in restoring function and minimizing injury would really have a powerful long-term impact.”
