Xoc Pharmaceuticals (Xoc) is developing XC130-A10H, a novel molecule, for the treatment of Parkinson’s disease (PD). Effects on rotational behavior measures are assessed and compared with the reference dopamine agonist compound lisuride.  

Lisuride infusion was demonstrated by Stocchi et al (Brain (2002), 125, 2058-2066) to produce a significant reduction in both motor fluctuations and dyskinesia in patients receiving lisuride and levodopa for 4 years compared with patients on levodopa therapy alone. In addition, the mean UPDRS scores remained the same for the lisuride-levodopa patients but deteriorated in patients on levodopa only. Due to its short half-life and 5-HT_2B agonistic character (associated with cardiovascular fibrotic complications), lisuride was not commercially developed as a Parkinson’s disease therapy.

XC130-A10H is being developed as an orally administered long lasting partial dopamine agonist for the treatment of Parkinson’s disease with the potential to provide therapy similar to lisuride.  XC130-A10H is engineered to delay the commencement of levodopa administration, lower the levodopa dose for late stage patients, and avoid undesirable side effects common to the existing dopamine agonist therapies. XC130-A10H would be the first novel dopamine agonist developed for the treatment of Parkinson’s disease in more than 20 years.

Unilateral 6-OHDA lesioned rats were acutely treated with XC130-A10H or lisuride alone or combination with levodopa.  The treatment effects on rotational behavior in the model were evaluated.

XC130-A10H showed efficacy similar to lisuride with similar effects on rotational behavior in the unilateral 6-OHDA model as a monotherapy, as well as in conjunction with reduced-dose levodopa therapy. 

The evaluation of XC130-A10H in the unilateral 6-OHDA model strongly suggests that XC130-A10H could be an important novel addition to therapy throughout the time course of Parkinson’s disease.