{"entity": "publication", "iuid": "8958e7d7d53b47f4bf40c30adcae897f", "timestamp": "2026-08-26T22:58:57.371Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8958e7d7d53b47f4bf40c30adcae897f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8958e7d7d53b47f4bf40c30adcae897f"}}, "title": "Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGF\u03b2 Signaling.", "authors": [{"family": "Peters", "given": "Sebastian", "initials": "S"}, {"family": "Kuespert", "given": "Sabrina", "initials": "S"}, {"family": "Wirkert", "given": "Eva", "initials": "E"}, {"family": "Heydn", "given": "Rosmarie", "initials": "R"}, {"family": "Jurek", "given": "Benjamin", "initials": "B"}, {"family": "Johannesen", "given": "Siw", "initials": "S"}, {"family": "Hsam", "given": "Ohnmar", "initials": "O"}, {"family": "Korte", "given": "Sven", "initials": "S"}, {"family": "Ludwig", "given": "Florian Timo", "initials": "FT"}, {"family": "Mecklenburg", "given": "Lars", "initials": "L"}, {"family": "Mrowetz", "given": "Heike", "initials": "H"}, {"family": "Altendorfer", "given": "Barbara", "initials": "B"}, {"family": "Poupardin", "given": "Rodolphe", "initials": "R"}, {"family": "Petri", "given": "Susanne", "initials": "S"}, {"family": "Thal", "given": "Dietmar R", "initials": "DR"}, {"family": "Hermann", "given": "Andreas", "initials": "A"}, {"family": "Weishaupt", "given": "Jochen H", "initials": "JH"}, {"family": "Weis", "given": "Joachim", "initials": "J"}, {"family": "Aksoylu", "given": "Inci Sevval", "initials": "IS"}, {"family": "Lewandowski", "given": "Sebastian A", "initials": "SA"}, {"family": "Aigner", "given": "Ludwig", "initials": "L"}, {"family": "Bruun", "given": "Tim-Henrik", "initials": "TH"}, {"family": "Bogdahn", "given": "Ulrich", "initials": "U", "orcid": "0000-0003-0826-7482", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc6c62ee47ff40bb94838e1ad5e18ed7.json"}}], "type": "journal article", "published": "2021-07-00", "journal": {"title": "Neurotherapeutics", "issn": "1878-7479", "volume": "18", "issue": "3", "pages": "1963-1979", "issn-l": null}, "abstract": "Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGF\u03b2-RII (Transforming Growth Factor-Receptor Type II) specific LNA-antisense oligonucleotide (\"locked nucleotide acid\"-\"NVP-13\"), which reduces TGF\u03b2-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX\u00ae cells) in vitro. After we injected cynomolgus non-human primates repeatedly i.th. with NVP-13 in a preclinical regulatory 13-week GLP-toxicity program, we could specifically downregulate TGF\u03b2-RII mRNA and protein in vivo. Subsequently, we observed a dose-dependent upregulation of the neurogenic niche activity within the hippocampus and subventricular zone: human neural progenitor cells showed significantly (up to threefold over control) enhanced differentiation and cell numbers. NVP-13 treatment modulated canonical and non-canonical TGF\u03b2 pathways, such as MAPK and PI3K, as well as key transcription factors and epigenetic factors involved in stem cell maintenance, such as MEF2A and pFoxO3. The latter are also dysregulated in clinical neurodegeneration, such as amyotrophic lateral sclerosis. Here, we provide for the first time in vitro and in vivo evidence for a novel translatable approach to treat neurodegenerative disorders by modulating neurogenesis.", "doi": "10.1007/s13311-021-01045-2", "pmid": "33860461", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8609055"}, {"db": "pii", "key": "S1878-7479(23)00783-3"}], "notes": [], "created": "2026-08-21T11:09:15.333Z", "modified": "2026-08-21T11:09:15.397Z"}