- Toxic Aβ-oligomeres are their specific targets; additionally D3 and its derivates have in vitro less effects on the concentration of Aβ-monomeres, those presumably show a neuroprotective function.
- The Aß-species resulting from the treatment with D-peptides are non-toxic and non-amyloidogenic and do not support prions like propagation.
- Due to this characteristic D-peptides are substantially more precise for the disease-causing agent and reduce the risk of possible side effects, especially in long-term treatment.
Like other research groups worldwide we are working on drug development for the treatment of Alzheimer's disease. By mirror image phage display we identified a d-enantiomeric peptide out of a library of around one billion peptides, which in contrast to other therapeutic approaches targets the specific reduction of A-Beta-oligomers.
D3 and D3 Derivatives have important advantages compared to other therapeutic substances, which are currently tested in clinical trials:
Furthermore D-peptides have the advantage to be more protease resistant and less immunogenic than the respective L-enantiomers.
The in vitro studies as well as the in vivo studies with transgenic „Alzheimer"-mice show very promising results, therefore in the near future a D3-Derivate will be tested in a phase I clinical trial in humans.
For D3 it could be already shown in vitro, that the formation of Aβ-fibrils and the toxic effect of Aβ-aggregates in cell culture is reduced. The treatment of transgenic „Alzheimer"-mice with D3 leads to a significant reduction of plaque load and inflammation reaction in the brain of the mice, additionally an improved performance in memory and cognition occurred.
The in vivo Studies are carried out in close collaboration with Dr. Willuweit and H Prof. Dr. Langen (INM-4 -Forschungszentrum Jülich) and Prof. van Groen (University of Alabama).
(A) Influences of D3 on Aβ-load in brain tissue sections of transgenic APP-PSΔE9 mice. Saline (Control), or D3 were infused in the brains of the mice for four weeks. Please note the decrease in Aβ staining in the D3 infused brain compared to the control brains. (van Groen et al. 2008) (B) Four months old mice had an Alzet minipump implanted under the skin with tubing inserted into the stomach, delivering the D3 peptide for the treated group and delivering saline solution for the control group. The escape latency is the time, which the D3 treated (open circles) and untreated (filled circles) mice needed to find the hidden platform in the Morris water maze assay. (Funke et al. 2010)