AIM Biologicals System Does Well in Early NMOSD Tests

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Autoimmunity Modifying (AIM) Biologicals, an experimental platform that Aeterna Zentaris is developing to treat autoimmune diseases like neuromyelitis optica spectrum disorder (NMOSD), showed proof-of-concept activity in cell and mouse models of NMOSD, new data show.

The findings were presented at the 13th International Congress on Autoimmunity, held earlier this month in Athens, Greece, in a poster titled, “Antigen presentation on MHC class Ib-related molecules induces Aquaporin-4-specific regulatory T cells in PBMC and prevents experimental autoimmune encephalomyelitis in mice.”

“There remains strong unmet medical need to provide treatment options for patients diagnosed with NMOSD, a rare but potentially devastating autoimmune condition. Given the severe impact NMOSD can have on people, we are very encouraged by the proof-of concept our AIM Biologicals program has demonstrated in both in vitro [in dishes] and mouse models,” Klaus Paulini, PhD, Aeterna’s CEO, said in a press release.

For the immune system, the world is black-and-white: everything that is a normal part of the body should be left alone, or “tolerated,” and anything else is assumed to be a threat and is attacked. Autoimmune diseases like NMOSD are effectively a breakdown of immune tolerance, with the immune system attacking the body’s own healthy tissue. NMOSD is driven mainly by immune cells that make antibodies targeting a brain protein called AQP4.

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There is a notable exception to the immune system’s rule of attacking everything that isn’t a normal part of the body: during pregnancy, a whole other organism — the fetus — is growing inside the body. A number of mechanisms have evolved to induce tolerance for the developing fetus, preventing the immune system from interfering with pregnancy.

The AIM Biologicals system takes advantage of one of these mechanisms. The system involves pairing a protein that is targeted in autoimmune disease (e.g., AQP4 in NMOSD) with a protein called HLA-G, which binds to receptors on immune cells called T-cells.

This is expected to induce the T-cells to grow into AQP4-specific regulatory T-cells. Regulatory T-cells, or Tregs, are a type of immune cell that specifically acts to dampen inflammatory responses and promote tolerance.

Here, researchers tested AQP4-loaded AIM Biologicals system using human immune cells in dishes, and also in mouse models of NMOSD.

Results showed that the experimental treatment promoted the development of Tregs, with treated cells producing less of the pro-inflammatory molecule IFN-gamma and more of the anti-inflammatory protein IL-10. In experimental autoimmune encephalitis (EAE) models, a mouse disease used to model autoimmune neurological diseases such as NMOSD, the treatment also eased symptoms and reduced inflammation in the spinal cord.

NMOSD is similar to another autoimmune neurological disease called MOG antibody disease (MOGAD), which is driven by an autoimmune attack targeting the protein MOG. Additional experiments using the AIM Biologicals system loaded with MOG similarly indicated that the system could reduce autoimmune inflammation in relevant models.

“Mouse-adapted AIM Biologicals selectively induce IL-10, inhibit IFN-[gamma] secretion in cognate T cells, inhibit EAE symptoms and spinal cord inflammation and eliminate MOG-specific autoantibodies in [MOG-specific] EAE models,” the researchers concluded.

“We are very pleased with these pre-clinical proof-of-concept results which help to inform our research moving forward to define a development candidate. As demonstrated in these pre-clinical studies, we believe that Aquaporin-4-specific AIM Biologicals have the potential to provide targeted immunosuppression in NMOSD,” said Valentin Bruttel, PhD. Bruttel is a researcher at the University of Wuerzburg in Germany who presented the poster.

Aeterna, through its subsidiary Aeterna Zentaris GmbH, acquired the experimental therapy platform from the university last year.

“We look forward to advancing this important program with our exclusive licensee, Aeterna, to potentially meet an indication where there remains unmet medical need,” Bruttel added.