Anti-inflammatory Molecule Can Pass Brain Barrier, May Treat MS

A potential anti-inflammatory treatment, xB3-IL-1RA was able to reach the central nervous system of a rodent model of multiple sclerosis (MS), and with repeat doses delay disease onset and ease clinical symptoms, according to the investigational therapy’s developer Bioasis Technologies.

These findings support the utility of Bioasis’ xB3 peptide platform in helping to deliver medicines into the brain and spinal cord (the central nervous system or CNS) through the blood-brain barrier — a highly selective membrane that regulates the passage of molecules into the specialized environment of nerve cells.

“These data further confirm the ability of the xB3 delivery platform to enhance the delivery of large molecule therapeutics into CNS compartments with demonstrated disease-relevant efficacy,” Deborah Rathjen, PhD, executive chair of the company’s board, said in a press release.

“We are progressing these data and believe that xB3-IL-1RA holds promise for the treatment of a broad range of neuroinflammatory diseases,” Rathjen added.

In MS, an abnormal immune response triggers inflammation in the CNS that damages nerve fibers and the fatty substance that surrounds and insulates them, known as the myelin sheath. When nerve fibers or myelin are damaged, messages within the CNS are altered or stopped, leading to the disease’s characteristic symptoms.

Interleukin-1-beta (IL-1-beta), an immune signaling protein, is a pro-inflammatory molecule shown to be implicated in several autoimmune and neuroinflammatory diseases, such as MS. The IL-1 receptor antagonist (IL-1RA) is a protein that binds and blocks the cell surface IL-1 receptor, preventing IL-1-beta from sending inflammatory signals.

But as a potential anti-inflammatory therapy, IL-1RA on its own cannot enter the CNS due to the blood-brain barrier.

Melanotransferrin (MTf) is a protein found on the surface of cells that form the blood-brain barrier, and it acts as a carrier to transport substances across the barrier and into the CNS. While MTf is seen as a potential way of facilitating the transport of medicines across the blood-brain barrier, MTf itself is a large protein. Its very size makes it challenging to attach biological therapies.

Recommended Reading

August 12, 2020 News by Steve Bryson, PhD

Inflammation Drives Nerve Damage in Early MS, Imaging Study Shows

Recently, scientists at Bioasis and colleagues published a study demonstrating how a specific fragment of MTf can be readily attached to medicines and help them cross the blood-brain barrier. In the study, IL-1RA attached to the MTf fragment — together named xB3-IL-1RA — and successfully entered the CNS, where it reduced nerve-based pain in a mouse model. Notably, administration of IL-1RA alone did not elicit pain relief.

Based on these results, the company tested xB3-IL-1RA in an established rodent model of MS called experimental allergic encephalomyelitis (EAE), in which autoimmune attacks on myelin and nerve fibers are induced.

Compared with control animals, multiple doses of xB3-IL-1RA — given during the initial phase of the disease — delayed further disease onset in the rodents, and lowered overall clinical symptom scores, Bioasis reported in its release.

These results support the utility of xB3-IL-1RA to treat diseases such as MS and other inflammatory diseases involving the CNS. Furthermore, according to Bioasis, the xB3 delivery platform has the potential to aid in the treatment of brain cancers as it can deliver large molecule biologics across the blood-brain barrier.