Antiparkinsonian effects of the "Radiprodil and Tozadenant" combination in MPTP-treated marmosets

作者：Michel Anne^*; Nicolas Jean Marie; Rose Sarah; Jackson Michael; Colman Peter; Brione Willy; Sciberras David; Muglia Pierandrea; Scheller Dieter K; Citron Martin; Downey Patrick

来源：PLos One, 2017, 12(8): e0182887.

DOI：10.1371/journal.pone.0182887

Objective
Investigate a combination of two clinically tested drugs, the NR2B antagonist Radiprodil and the A(2A) antagonist Tozadenant in the MPTP-treated marmoset model of Parkinson's Disease (PD).
Background
In PD, there remains a need for the development of non-dopaminergic drugs to effectively treat the motor symptoms without the induction of L-Dopa-induced motor complications.
Methods
Clinically relevant doses of Radiprodil and Tozadenant were given both alone and in combination without the addition of L-Dopa, and the antiparkinsonian efficacy of the treatments was assessed in a primate model of PD.
Results
When compared to the drugs tested alone, the drug combination led to a significant increase of motor activity and an improvement of motor disability in MPTP-treated marmosets. In addition, the motor restoration brought about by the combination was almost completely devoid of dyskinesia. Interestingly, treated primates were not overstimulated, but were able to move normally when motivated by the exploration of novel objects.
Conclusion
We have demonstrated in a primate model that, the "Radiprodil/Tozadenant" combination significantly improves motor activity, extending previous results obtained in unilaterally lesioned 6-OHDA-rats. The strength of the preclinical data accumulated so far suggests that the use of such an A(2A) and NR2B antagonist combination could bring significant motor improvement to PD patients, without inducing the motor complications induced by L-Dopa therapy. Although encouraging, these preclinical data need to be confirmed in the clinic.

• 出版日期2017-8-30