Pekka Kallunki, Florence Sotty, Katarina Willén, Michal Lubas, Laurent David, Malene Ambjørn, Ann-Louise Bergström, Louise Buur, Ibrahim Malik, Steffen Nyegaard, Thomas Thiilmark Eriksen, Berit O. Krogh, Jeffrey B. Stavenhagen, Kathrine J. Andersen, Lars Ø. Pedersen, Ersoy Cholak, Edward N. van den Brink, Rik Rademaker, Tom Vink, David Satijn, Paul W.H.I. Parren, Søren Christensen, Line R. Olsen, Josefine N. Søderberg, Sandra Vergo, Allan Jensen, Jan Egebjerg, Pernille Gry Wulff-Larsen, Mikkel N. Harndahl, Dina S. M. Damlund, Kaare Bjerregaard-Andersen, Karina Fog
{"title":"合理选择单克隆α-突触核蛋白抗体amlenetug (Lu AF82422)治疗α-突触核蛋白病","authors":"Pekka Kallunki, Florence Sotty, Katarina Willén, Michal Lubas, Laurent David, Malene Ambjørn, Ann-Louise Bergström, Louise Buur, Ibrahim Malik, Steffen Nyegaard, Thomas Thiilmark Eriksen, Berit O. Krogh, Jeffrey B. Stavenhagen, Kathrine J. Andersen, Lars Ø. Pedersen, Ersoy Cholak, Edward N. van den Brink, Rik Rademaker, Tom Vink, David Satijn, Paul W.H.I. Parren, Søren Christensen, Line R. Olsen, Josefine N. Søderberg, Sandra Vergo, Allan Jensen, Jan Egebjerg, Pernille Gry Wulff-Larsen, Mikkel N. Harndahl, Dina S. M. Damlund, Kaare Bjerregaard-Andersen, Karina Fog","doi":"10.1038/s41531-024-00849-1","DOIUrl":null,"url":null,"abstract":"<p>Amlenetug (Lu AF82422) is a human monoclonal antibody targeting α-synuclein in clinical development for multiple system atrophy. We describe a series of studies that characterize its functional properties and supported its selection as a viable clinical candidate. Amlenetug inhibits seeding induced in mouse primary neurons by various α-synuclein fibrillar assemblies and by aggregates isolated from MSA brain homogenate. In vivo, both co-injection of amlenetug with α-synuclein assemblies in mouse brain and peripheral administration inhibit α-synuclein seeding. Amlenetug inhibits uptake of α-synuclein seeds as well as accumulation of C-terminal truncated α-synuclein seeds and demonstrates binding to monomeric, aggregated, and truncated forms of human α-synuclein. The epitope of amlenetug was mapped to amino acids 112-117 and further characterized by crystallographic structure analysis. Based on our data, we hypothesize that targeting α-synuclein will potentially slow further disease progression by inhibiting further pathology development but be without impact on established pathology and symptoms.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"45 1","pages":""},"PeriodicalIF":6.7000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rational selection of the monoclonal α-synuclein antibody amlenetug (Lu AF82422) for the treatment of α-synucleinopathies\",\"authors\":\"Pekka Kallunki, Florence Sotty, Katarina Willén, Michal Lubas, Laurent David, Malene Ambjørn, Ann-Louise Bergström, Louise Buur, Ibrahim Malik, Steffen Nyegaard, Thomas Thiilmark Eriksen, Berit O. Krogh, Jeffrey B. Stavenhagen, Kathrine J. Andersen, Lars Ø. Pedersen, Ersoy Cholak, Edward N. van den Brink, Rik Rademaker, Tom Vink, David Satijn, Paul W.H.I. Parren, Søren Christensen, Line R. Olsen, Josefine N. Søderberg, Sandra Vergo, Allan Jensen, Jan Egebjerg, Pernille Gry Wulff-Larsen, Mikkel N. Harndahl, Dina S. M. Damlund, Kaare Bjerregaard-Andersen, Karina Fog\",\"doi\":\"10.1038/s41531-024-00849-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Amlenetug (Lu AF82422) is a human monoclonal antibody targeting α-synuclein in clinical development for multiple system atrophy. We describe a series of studies that characterize its functional properties and supported its selection as a viable clinical candidate. Amlenetug inhibits seeding induced in mouse primary neurons by various α-synuclein fibrillar assemblies and by aggregates isolated from MSA brain homogenate. In vivo, both co-injection of amlenetug with α-synuclein assemblies in mouse brain and peripheral administration inhibit α-synuclein seeding. 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Rational selection of the monoclonal α-synuclein antibody amlenetug (Lu AF82422) for the treatment of α-synucleinopathies
Amlenetug (Lu AF82422) is a human monoclonal antibody targeting α-synuclein in clinical development for multiple system atrophy. We describe a series of studies that characterize its functional properties and supported its selection as a viable clinical candidate. Amlenetug inhibits seeding induced in mouse primary neurons by various α-synuclein fibrillar assemblies and by aggregates isolated from MSA brain homogenate. In vivo, both co-injection of amlenetug with α-synuclein assemblies in mouse brain and peripheral administration inhibit α-synuclein seeding. Amlenetug inhibits uptake of α-synuclein seeds as well as accumulation of C-terminal truncated α-synuclein seeds and demonstrates binding to monomeric, aggregated, and truncated forms of human α-synuclein. The epitope of amlenetug was mapped to amino acids 112-117 and further characterized by crystallographic structure analysis. Based on our data, we hypothesize that targeting α-synuclein will potentially slow further disease progression by inhibiting further pathology development but be without impact on established pathology and symptoms.
期刊介绍:
npj Parkinson's Disease is a comprehensive open access journal that covers a wide range of research areas related to Parkinson's disease. It publishes original studies in basic science, translational research, and clinical investigations. The journal is dedicated to advancing our understanding of Parkinson's disease by exploring various aspects such as anatomy, etiology, genetics, cellular and molecular physiology, neurophysiology, epidemiology, and therapeutic development. By providing free and immediate access to the scientific and Parkinson's disease community, npj Parkinson's Disease promotes collaboration and knowledge sharing among researchers and healthcare professionals.