{"entity": "journal", "iuid": "977c7d7a121547158bac6568b1afff90", "timestamp": "2026-08-26T22:46:29.304Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Neurotherapeutics.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Neurotherapeutics"}}, "title": "Neurotherapeutics", "issn": "1878-7479", "issn-l": null, "publications_count": 2, "publications": [{"entity": "publication", "iuid": "8958e7d7d53b47f4bf40c30adcae897f", "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"}, {"entity": "publication", "iuid": "fdb57fc1916845e7ae6ee2739913663c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fdb57fc1916845e7ae6ee2739913663c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fdb57fc1916845e7ae6ee2739913663c"}}, "title": "Characterization of More Selective Central Nervous System Nrf2-Activating Novel Vinyl Sulfoximine Compounds Compared to Dimethyl Fumarate.", "authors": [{"family": "Carlstr\u00f6m", "given": "Karl E", "initials": "KE"}, {"family": "Chinthakindi", "given": "Praveen K", "initials": "PK"}, {"family": "Espinosa", "given": "Bel\u00e9n", "initials": "B"}, {"family": "Al Nimer", "given": "Faiez", "initials": "F"}, {"family": "Arn\u00e9r", "given": "Elias S J", "initials": "ESJ"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI"}, {"family": "Piehl", "given": "Fredrik", "initials": "F"}, {"family": "Johansson", "given": "Katarina", "initials": "K"}], "type": "comparative study", "published": "2020-07-00", "journal": {"title": "Neurotherapeutics", "issn": "1878-7479", "volume": "17", "issue": "3", "pages": "1142-1152", "issn-l": null}, "abstract": "The Nrf2 transcription factor is a key regulator of redox reactions and considered the main target for the multiple sclerosis (MS) drug dimethyl fumarate (DMF). However, exploration of additional Nrf2-activating compounds is motivated, since DMF displays significant off-target effects and has a relatively poor penetrance to the central nervous system (CNS). We de novo synthesized eight vinyl sulfone and sulfoximine compounds (CH-1-CH-8) and evaluated their capacity to activate the transcription factors Nrf2, NF\u03baB, and HIF1 in comparison with DMF using the pTRAF platform. The novel sulfoximine CH-3 was the most promising candidate and selected for further comparison in vivo and later an experimental model for traumatic brain injury (TBI). CH-3 and DMF displayed comparable capacity to activate Nrf2 and downstream transcripts in vitro, but with less off-target effects on HIF1 from CH-3. This was verified in cultured microglia and oligodendrocytes (OLs) and subsequently in vivo in rats. Following TBI, DMF lowered the number of leukocytes in blood and also decreased axonal degeneration. CH-3 preserved or increased the number of pre-myelinating OL. While both CH-3 and DMF activated Nrf2, CH-3 showed less off-target effects and displayed more selective OL associated effects. Further studies with Nrf2-acting compounds are promising candidates to explore potential myelin protective or regenerative effects in demyelinating disorders.", "doi": "10.1007/s13311-020-00855-0", "pmid": "32394330", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7609514"}, {"db": "pii", "key": "S1878-7479(23)01329-6"}], "notes": [], "created": "2026-08-20T06:40:46.169Z", "modified": "2026-08-20T06:40:46.239Z"}], "created": "2026-08-20T06:40:46.199Z", "modified": "2026-08-20T06:40:46.199Z"}