Novel therapeutic strategies in Parkinson's disease.

PD is a neurodegenerative disorder triggered by genetic and/or environmental factors and the pathological processes begin many years before motor symptom manifestation. Several drugs are available to treat PD, but there are still many aspects of the disease that have not been well addressed. These include nonmotor symptoms, disease progression, and preventing levodopa-induced motor complications. Besides the concept of continuous dopaminergic stimulation, the benefit of which has not been proved in clinical settings (see the STRIDE-PD trial), the nondopaminergic drugs offer promising alternatives to dopaminergic medication. However, modification and further development of dopaminergic molecules may provide significant symptomatic improvement and improved quality of life. In this review, we summarized new treatments that are in the pipeline, with patients being recruited for clinical trials. Among the compounds being studied are well-known ones (e.g., folic acid or methylphenidate), which have been used in other diseases, and newly developed drugs with known mode of action (e.g., the dopamine agonist aplindore) or compounds with completely new mechanisms, which have not yet been used in clinical settings (e.g., levetiracetam or Neu 120). A major breakthrough in treating Parkinson's disease cannot be expected with molecules from the first two cases, whereas significant clinical benefits can be predicted with the drugs in the last group. However, without these large-scale, well-designed, multicenter trials, the promising preclinical results cannot be directly adopted in patient care. Hopefully, some of these trials will end soon with positive results, and certain drugs will become available with which to treat PD patients, although still many aspects (e.g., the most problematic one, the question of neuroprotection) still need to be addressed.