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Synthetic Antibody Limits M.S. Inflammation

Neurons

(commonfund.nih.gov)

6 May 2020. An artificial antibody is shown in lab mice to reduce inflammation similar to multiple sclerosis in the brain and activate myelin cells in the spinal cord. Results of the study by researchers at University of Miami in Florida appear in the 4 May issue of the Journal of Neuroinflammation.

A team from Miami’s medical school led by Roberta Brambilla and Robert Keane tested a synthetic humanized antibody code-named IC100 made by ZyVersa Therapeutics Inc., a biotechnology company in Weston, Florida, as a treatment candidate for multiple sclerosis. IC100 targets inflammasomes, protein systems that send chemical signals in the immune system triggering inflammation.

Multiple sclerosis is an autoimmune condition, where the immune system attacks the central nervous system and damages myelin, the fatty, protective substance around nerve fibers, as well as nerve cells themselves. Scar tissue from inflammation of damaged myelin, known as sclerosis, distorts the nerve signals sent to and from the brain and spinal cord, causing symptoms ranging from mild numbness to loss of vision or paralysis.

ZyVersa designed IC100 to block ASC, a key protein component of inflammasomes that starts a cascade of events, first by providing a scaffold and attracting Caspase1 proteins. Caspase1 proteins promote secretion of enzymes that encourage an immune response, but also inflammation. Inflammasomes form and become active when triggered by invading pathogens, calling on the adaptive immune system when the body’s innate immunity is not sufficient to battle the invaders, and also with autoimmune disorders such as multiple sclerosis.

The study tested IC100 in lab mice induced with experimental autoimmune encephalomyelitis, or EAE, a condition similar to multiple sclerosis. The mice were given IC100 as injections in three increasing doses and were followed for 35 days. For comparison, another group of mice were given injections with the carrier chemical, but not IC100.

The Miami team found IC100 at the middle and highest doses, 30 and 45 milligrams per kilogram, successfully crosses the blood-brain barrier to permeate the brain and spinal cord and accumulate in sufficient concentrations to produce therapeutic effects. Those effects include fewer immune system cells associated with innate and adaptive immunity, suggesting limited production of ASC proteins that start the cascade of enzymes and cytokines promoting inflammation.

In addition, mice receiving the middle IC100 (30 milligram) dose activate myelin cells entering the spinal cord. Moreover, at that dosage, IC100 recipient mice activate fewer microglia, macrophages-like cells in the central nervous system that also encourage inflammation, and exhibit fewer functional EAE symptoms resembling multiple sclerosis.

The authors conclude ASC is a promising target for multiple sclerosis or M.S. treatments. “M.S. is a progressive disease resulting in physical, cognitive, and psychological disabilities that greatly impair quality of life,” says Keane, also a scientific adviser to Zyversa, in a company statement. “Based on the EAE results we are optimistic about the potential of IC100 as an effective treatment option for M.S. We look forward to working with ZyVersa to progress its development into the clinic.”

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