| First Author | Schemmert S | Year | 2019 |
| Journal | Neurobiol Dis | Volume | 124 |
| Pages | 36-45 | PubMed ID | 30391539 |
| Mgi Jnum | J:277801 | Mgi Id | MGI:6295620 |
| Doi | 10.1016/j.nbd.2018.10.021 | Citation | Schemmert S, et al. (2019) Deceleration of the neurodegenerative phenotype in pyroglutamate-Abeta accumulating transgenic mice by oral treatment with the Abeta oligomer eliminating compound RD2. Neurobiol Dis 124:36-45 |
| abstractText | Alzheimer's disease, a multifactorial incurable disorder, is mainly characterised by progressive neurodegeneration, extracellular accumulation of amyloid-beta protein (Abeta), and intracellular aggregation of hyperphosphorylated tau protein. During the last years, Abeta oligomers have been claimed to be the disease causing agent. Consequently, development of compounds that are able to disrupt already existing Abeta oligomers is highly desirable. We developed d-enantiomeric peptides, consisting solely of d-enantiomeric amino acid residues, for the direct and specific elimination of toxic Abeta oligomers. The drug candidate RD2 did show high oligomer elimination efficacy in vitro and the in vivo efficacy of RD2 was demonstrated in treatment studies by enhanced cognition in transgenic mouse models of amyloidosis. Here, we report on the in vitro and in vivo efficacy of the compound towards pyroglutamate-Abeta, a particular aggressive Abeta species. Using the transgenic TBA2.1 mouse model, which develops pyroglutamate-Abeta(3-42) induced neurodegeneration, we are able to show that oral RD2 treatment resulted in a significant deceleration of the progression of the phenotype. The in vivo efficacy against this highly toxic Abeta species further validates RD2 as a drug candidate for the therapeutic use in humans. |
