COYA 302 combination therapy tames brain inflammation in mice

19 September 2024

An oversized human hand holds a mouse alongside a rack with three filled vials.

Subcutaneous, or under-the-skin, injections of COYA 302, a combination therapy in development by Coya Therapeutics, were found to reduce excessive inflammation and immune cell activation in a mouse model of Parkinson’s disease.

These beneficial effects were observed in the nigrostriatal pathway, a brain circuit responsible for motor control, and demonstrated significant anti-inflammatory effects, according to the researchers.

COYA 302, originally developed as a treatment for amyotrophic lateral sclerosis (ALS), combines low-dose interleukin-2 (IL-2) and the fusion protein CTLA-4 Ig (abatacept) for subcutaneous administration.

The combination of IL-2 and abatacept is expected to limit overactivation of the immune system in the brain and slow disease progression by boosting the activity of regulatory T-cells, known as Tregs. A type of immune cells, Tregs help keep inflammation under control.

“We believe that the ability of peripherally administered biologics (COYA 302) that potently and directly ameliorate the inflammatory milieu in the brain translates to strategies to suppress [neuroinflammation in the brain and spinal cord] beyond [Parkinson’s],” Arun Swaminathan, PhD, Coya’s chief business officer and incoming CEO, said in a company press release.

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In Parkinson’s, excessive inflammation can trigger a series of events that are damaging to dopaminergic neurons, the nerve cells that produce the chemical messenger dopamine, which is needed to signal motor control. A lack of dopamine results in motor symptoms, such as tremor, stiffness, slowness, and poor coordination and balance that are hallmarks of Parkinson’s.

What exactly causes neuroinflammation is unclear, but scientists believe that overly reactive microglia — brain-resident immune cells — and astrocytes, the star-shaped cells that provide support to neurons, may play a role. Too few or poorly functioning Tregs in the brain also may explain why the body fails to keep inflammation in check.

Coya already had been developing COYA 302 to restore the numbers and function of Tregs in ALS, Alzheimer’s disease, and frontotemporal dementia, a form of dementia. Earlier this year, the program was extended to Parkinson’s, with plans to file for clearance to start clinical testing in patients for 2025, according to the company’s website.

Before that occurs, Coya is conducting preclinical testing of the combination therapy for Parkinson’s.

In this inflammatory mouse model of Parkinson’s, subcutaneous injections of COYA 302 significantly reduced inflammation along the nigrostriatal pathway, a circuit of dopaminergic neurons that connects the substantia nigra with another brain region called the dorsal striatum and is needed for motor control.

Treatment with COYA 302 also resulted in reduced activation of microglia as well as reduced numbers and activation of astrocytes in the substantia nigra and dorsal striatum. Those results suggest the therapy may directly tame the immune cells that cause inflammation in Parkinson’s.

The company plans to publish these results in a peer-reviewed journal and to advance testing of COYA 302 into additional preclinical models of Parkinson’s.

The post COYA 302 combination therapy tames brain inflammation in mice appeared first on Parkinson's News Today.

https://parkinsonsnewstoday.com/news/coya-302-combination-therapy-tames-brain-inflammation-mice/

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