On November 4, 2021 AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical-stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, reported it is extending its research partnership with leading scientists at the Center for Neurodegenerative Disease Research at the Perelman School of Medicine at the University of Pennsylvania (Penn) (Press release, AC Immune, NOV 4, 2021, View Source [SID1234594477]). The partnership is focused on studying the pathological mechanism of transactive response DNA binding protein 43 kDa (TDP-43) misfolding, aggregation and cell-to-cell transmission.

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The successful first two years of the collaboration between AC Immune and Penn demonstrated that TDP-43 aggregates from the brains of donors with different TDP-43 proteinopathies have distinct seeding and spreading capacity in vivo. The proteinopathies studied included amyotrophic lateral sclerosis (ALS) and different subtypes of frontotemporal lobar degeneration-TDP (FTLD-TDP). These results confirm the existence of distinct pathogenic TDP-43 species and have been published in Neuropathology and Applied Neurobiology1.

In extending the collaboration with Penn, we aim to further understand the role of these distinct pathogenic TDP-43 species in the different TDP-43 proteinopathies. Through the development of novel experimental models, AC Immune and Penn hope to unravel the underlying mechanisms of cell-to-cell transmission of TDP-43 pathology that could provide new therapeutic strategies to target TDP-43-related proteinopathies.

Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: "We are very excited to extend our collaboration with the outstanding team of Professor Virginia Lee and Dr. Sílvia Porta at the University of Pennsylvania, continuing our exploration into the mechanisms and pathology driven by TDP-43. Our work has led to a better understanding of TDP-43 pathologies, which supports ACoImmune’s aim as we advance one of the industry’s broadest and most diversified pipeline with novel therapeutic and diagnostic approaches against neurodegenerative diseases."

Prof. Virginia M.Y. Lee, Director of the Center for Neurodegenerative Disease Research at the University of Pennsylvania, commented: "TDP-43 pathology is strongly associated with cognitive decline and episodic memory loss in neurodegenerative diseases, such as FTLD and ALS, and also plays an important role in Alzheimer’s disease. Our collaboration with AC Immune shows why industry sponsorship of academic research is vital for funding studies to advance our understanding into such an important target as TDP-43."

AC Immune has a lead anti-TDP-43 antibody in preclinical development, which has shown significantly reduced levels of pathological form of TDP-43 in the brain and conferred neuroprotection in murine neurodegenerative disease models. The company is also developing a first-in-class TDP-43 positron emission tomography (PET) tracer.