Research demonstrates potential for anti-tau immunotherapy in treatment of Alzheimer's and other tau-driven diseases including progressive supranuclear palsy (PSP)



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Findings, combined with previous in vitro research, highlight important differences between tau antibodies
Expanding evidence base supports UCB’s decision to progress clinical studies of its anti-tau immunotherapy candidate in humans
Brussels, Belgium, May 2, 2019, 07:00 (CEST):  UCB Biopharma, and a team of scientists from Inserm (Institut national de la santé et de la recherche médicale, the French National Institute of Health and Medical Research), led by Dr. Luc Buée, CNRS research professor at the University of Lille, France, have demonstrated the beneficial effects of anti-tau immunotherapy in a murine model of Alzheimer's disease, published in the current online edition of the international scientific journal ‘Brain’.1

The research set out to evaluate two antibodies targeting tau in an in vivo model to determine their effects on disease onset and progression in mice injected with extracts from Alzheimer’s disease brains and a second mouse model designed to evaluate spread of disease.

The study found that the novel UCB antibody targeting a central epitope on tau effectively blocked the onset of disease in mice by preventing the formation of neurofibrillary tangles. The antibody also prevented the spread of pathologic tau protein to other parts of the brain in mice, which is commonly associated with disease progression in Alzheimer’s disease. The other antibody evaluated, which targeted a different tau epitope, was less efficacious at blocking tau-induced pathology, highlighting the impact of the choice of tau epitope on in vivo efficacy.

UCB has previously studied a series of antibodies against tau that have the in vitro ability to block tau aggregation2. In murine models, where the pathology is initiated by injecting brain extracts from patients with Alzheimer's disease, some antibodies pre-selected in vitro block tau aggregation. In addition, these antibodies prevent the spread of neuronal degeneration within the brain of the mouse.

Describing the research, Dr. Morvane Colin from the University of Lille, France, who co-directed this research with Dr. Jean-Philippe Courade of UCB explained: “Not all antibodies targeting tau are equally effective. Indeed, in this study and a previous in vitro study, antibodies targeting the most central part of tau protein showed potential for improved efficacy.”

Tau protein is one of the major proteins that aggregate to lead to neuronal death in many neurodegenerative diseases, including Alzheimer's disease and progressive supranuclear palsy. Immunotherapy targeting extracellular tau protein is a new and promising therapeutic approach for these pathologies.

Results from this animal study, coupled with the characterization of these antibodies by UCB, has supported the start of clinical studies in humans.

Dr. Martin Citron, Head UCB Neuroscience explained: “These data, when considered together with previously published in vitro studies, suggest that the choice of a tau epitope could be a critical determinant of therapeutic efficacy of tau antibodies. We are excited to progress our clinical program to explore the potential benefits of our anti-tau antibody in neutralizing pathological species present in brains of people with Alzheimer's disease and PSP.”

The journal paper is available online via the following link: https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awz100.  

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