Update on Positive Pre-Clinical Results From AIM Biologicals Development Program for the Potential Treatment of Parkinson’s Disease

Aeterna Zentaris Inc. recently provided an update on the positive results from pre-clinical studies of Aeterna’s Autoimmunity Modifying Biologicals (AIM Biologicals), for the potential treatment of Parkinson’s Disease (PD). As previously announced, the data were presented at IMMUNOLOGY2022, the annual event of the American Association of Immunologists, held on May 6-10, 2022, in Portland, OR.

“Under our collaboration with the University of Wuerzburg, Prof. Wischhusen, Prof. Chi Wang Ip, and their teams have provided data that we believe is important pre-clinical proof of concept for our AIM Biologicals platform,” said Dr. Klaus Paulini, Chief Executive Officer of Aeterna Zentaris. “In various in-vitro and in-vivo assays, the team has demonstrated the antigen-specific immune-modulatory activity of these HLA-G-based molecules. We are very pleased with the encouraging progress of our AIM Biologicals program and the potential utility for the treatment of PD.”

AIM Biologicals are targeted, highly specific autoimmunity-modifying therapeutics. The scientific concept behind this platform technology is “feto-maternal-tolerance.” During pregnancy, the immune system of mothers does not attack the fetus, which consists of 50% paternal proteins. For this, the immune system is not downregulated, but selectively de-sensibilized, thus ensuring that the mothers continue to be protected against infections.

For development as potential PD therapeutics, the company is utilizing, among others, an innovative animal model on neurodegeneration by α-synuclein-specific T cells in AAV-A53T-α-synuclein Parkinson’s disease mice, which has recently been published by our University of Wuerzburg research collaborators.

The abstract, titled α-synuclein peptides presented on chimeric MHC class Ib molecules prevent loss of substantia nigra neurons in an animal model for Parkinson’s disease,” outlines the data that was presented by Prof. Joerg Wischhusen, PhD, Head of the Laboratory of Experimental Tumor Immunology, Department of Obstetrics and Gynecology, School of Medicine, University of Wuerzburg. As previously announced, that abstract was accepted as a poster presentation and was also selected for an oral presentation at IMMUNOLOGY2022.

The pre-clinical study investigated whether novel, antigen-specific, tolerance-inducing biomolecules that present peptide antigens on MHC class Ib-related molecules can inhibit neurodegeneration and prevent PD in-vivo.

The pre-clinical data presented showed consistent effects in various in-vitro and in-vivo models, verifying the potential of HLA-G based molecules to induce antigen-specific immune-modulation. Treatment with such molecules (AIM Biologicals) lead to apoptosis of antigen-specific cytotoxic T cells and to the stimulation of regulatory T cells. In a new, innovative mouse model of Parkinson’s disease, treatment with α-Synuclein specific AIM Biologicals showed a trend towards improved motoric function, as well as significant induction of regulatory T cells and rescue of substantia nigra neurons.

“There is a growing interest in the induction of antigen-specific immunotolerance in neuroinflammatory diseases,” said Prof. Joerg Wischhusen. “Utilizing such therapeutic approaches is of particular interest in the potential treatment of PD, since currently available treatment options are symptomatic and immunomodulatory treatments have not yet been tested. We were pleased with the results from this study and believe the translational potential of this approach deserves further exploration.”

The abstract and poster can be accessed on the Publications page of the company’s website.

Aarkinson’s disease is a neurodegenerative movement disorder affecting over 7 million people worldwide. PD belongs to a family of disorders termed synucleinopathies, which exhibit a characteristic deposition of α-synuclein aggregates in so-called Lewy bodies. Degeneration of dopaminergic neurons in the substantia nigra (SN) leads to a loss of dopaminergic transmission in the striatum. Neuroinflammation is a well-established hallmark of the disease. Recent data provide growing evidence for a strong autoimmune component in PD, with α-synuclein-specific T cell responses playing a key role in disease progression.

AIM Biologicals utilizes a novel mechanism based on peptide antigens that are presented on MHC class I molecules, to selectively and efficiently induce antigen-specific tolerance. Based on this mechanism, the immunomodulating therapeutics are designed as optimized soluble molecules that can be adapted to selectively induce tolerance to various autoantigens. Pre-clinical studies conducted by the University of Wuerzburg thus far indicate that tolerance induction appears to be achieved via selective elimination of antigen-specific immune effector cells and via induction of antigen-specific regulatory T cells from naïve T cells. Accordingly, α-Synuclein-specific AIM Biologicals may have the potential to become a highly specific and effective treatment of PD.

Aeterna Zentaris is a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products focused on areas of significant unmet medical need. The company’s lead product, macimorelin (Macrilen; Ghryvelin), is the first and only US FDA- and European Commission-approved oral test indicated for the diagnosis of adult growth hormone deficiency (AGHD). The company is leveraging the clinical success and compelling safety profile of macimorelin to develop it for the diagnosis of childhood-onset growth hormone deficiency (CGHD), an area of significant unmet need, in collaboration with Novo Nordisk.

Aeterna Zentaris is dedicated to the development of therapeutic assets and has recently taken steps to establish a growing pre-clinical pipeline to potentially address unmet medical needs across a number of indications, including neuromyelitis optica spectrum disorder (NMOSD), Parkinson’s disease (PD), hypoparathyroidism, and amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease). Additionally, the company is developing an oral prophylactic bacterial vaccine against SARS-CoV-2 (COVID-19) and Chlamydia trachomatis. For more information, visit www.zentaris.com.