Table 2.
Current translational trials
| Agent or approach | Model | Sponsor | Action | Effect |
|---|---|---|---|---|
| BDNF mimetic or booster | ||||
| LM22A-4 | Mouse | Sigma-Aldrich; RSRT | Partial agonist of TrkB receptors | Improves breathing |
| RP103 (Cysteamine) | Mouse | Raptor Pharmaceuticals | Increases BDNF expression and release | Improves breathing |
| 5-HT1a receptor agonists | ||||
| Sarizotan | Mouse | Newron Pharmaceuticals | Agonist of 5-HT1 receptors | Improves breathing |
| NLX-101 | Mouse | Neurolixis | Agonist of 5-HT1 receptors | Improves breathing |
| NMDA receptor modulators | ||||
| GluN2A negative allosteric modulator | Mouse | Mnemosyne Pharmaceuticals | Negative allosteric modulater of GluN2A-containing NMDA receptors | Improved visual cortical function |
| Ketamine | Mouse | Approved drug | Noncompetitive antagonist of NMDA receptors | Improved breathing and locomotor function |
| Antidepressant | ||||
| REV-003 (Tianeptine) | Mouse | Revive Therapeutics | Atypical tricyclic antidepressant | Improves breathing |
| Gene therapy and “read-through” drugs | ||||
| Gene replacement | Mouse | Research Laboratories | Improvement of symptoms | Improvement of lifespan and behavioral symptoms |
| Read-through agents | In vitro (lymphocyte cell line from RTT; fibroblasts from knockin mice) | Research Laboratories | Skip premature STOP codon in nonsense mutations | In vitro expression of full length MeCP2 protein |
BDNF = brain-derived neurotrophic factor; TrkB = tropomyosin receptor kinase B; NMDA = N-methyl-D-aspartate; RTT = Rett syndrome; MeCP2 = methyl CpG binding protein 2