Anle138b | MODAG GmbH | Inhibits α-Syn oligomer formation | Small molecule | Phase 1 | NCT04208152: completed, results pending |
| | | | | NCT04685265: recruiting |
NPT200-11 | Neuropore Therapies Inc. | Interferes with α-Syn aggregation by displacing α-Syn from membranes | Small molecule | Phase 1 | NCT02606682: completed, results pending |
ENT-01 | Enterin, Inc | Interferes with α-Syn aggregation by displacing α-Syn from membranes | Small molecule | Phase 2 | NCT03047629: improvement in constipation (Hauser et al., 2019) |
Phase 2 | NCT04483479: recruiting |
Phase 2 | NCT03781791: recruiting |
| | | | Phase 1 in PD dementia | NCT03938922: active, not recruiting |
Trodusquemine | | Interferes with α-Syn aggregation by displacing α-Syn from membranes | Small molecule | Preclinical | Protects against α-Syn aggregation and paralysis in C. elegans overexpressing α-Syn (Perni et al., 2018) |
NPT088 | Proclara Biosciences | Binds aggregated proteins and disrupts the amyloid conformation | Small molecule | Preclinical in PD, but phase 1 in AD | Good safety and tolerability in patients with AD but no effect on markers of clinical progression (Michelson et al., 2019) |
VH14 | | Targets the NAC domain of α-Syn to interfere with aggregation and target α-Syn to the proteosome | Intrabody/nanobody | Preclinical | Rats injected with VH14 into the striatum had protection against injection of AAV-α-Syn into the striatum on measures of phosphorylated α-Syn and dopaminergic cell health (Chatterjee et al., 2018) |
SLS-007 peptides, S62 and S71 | Seelos Therapeutics | Interfere with α-Syn aggregation by targeting the NAC domain | Peptides | Preclinical | Prevent aggregation of α-Syn in cell culture (Sangwan et al., 2020) and are now being testing in animal models using an AAV delivery system |
EHT ± caffeine | | Increases activity of PP2A by inhibiting PME1 | Small molecules | Preclinical | Protective in transgenic α-Syn, MPTP treated and α-Syn preformed fibril treated mice on measures of dopaminergic cell integrity, neuroinflammation, and motor behavior (Lee et al., 2011, 2013; Yan et al., 2018) |
Deferiprone | University Hospital, Lille; ApoPharma; Imperial College London | Iron chelation | Small molecule | Pilot clinical study | Improved motor performance on the UPDRS (Devos et al., 2014) |
Phase 2/3 | Improved motor performance on the UPDRS (NCT00943748) (Grolez et al., 2015) |
Phase 2 | Trend in improvement in motor scores (NCT01539837)(Martin-Bastida et al., 2017) |
Phase 2 | NCT02728843: completed, results pending |
| | | | Phase 2 | NCT02655315: active, not recruiting |
PBT434 | Alterity Therapeutics | Iron attenuation | Small molecule | Phase 1 | Completed, results not yet published |
YTX-7739 | Yumanity Therapeutics | Inhibits stearoyl-CoA desaturase | Small molecule | Phase 1 | Active |
Cystamine | | Decreased α-Syn aggregation through blocking TG2 activity | Small molecule | Preclinical | Protective in mice treated with MPTP or 6-OHDA on measures of dopaminergic cell loss and generation of reactive oxygen species (Tremblay et al., 2006; Stack et al., 2008; Sun et al., 2010); in addition, overexpression of TG2 exacerbates α-Syn toxicity, whereas knockout of TG2 is protective against α-Syn toxicity in α-Syn transgenic mice, on measures of α-Syn aggregation, neuroinflammation, and motor performance (Grosso et al., 2014; Zhang et al., 2020a) |