PATHOLOGIES

Parkinson’s Disease

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, affecting about 1% of people over 60 and 4% over 80 years old worldwide. Most (90-95%) PD cases are idiopathic with no specific known cause, with the remaining cases being familial genetic forms. PD diagnosis remains clinical and based on the presence of motor features such as tremor, slowness of movements (bradykinesia), muscular rigidity, and postural instability. Other non-motor features include disorders involving cognition, mood, and behavior. Progression of PD is characterized by worsening of symptoms over time. The main pathophysiological features of PD include selective and progressive degeneration and death of dopaminergic neurons in the substantia nigra pars compacta, a region of the midbrain, resulting in dopamine deficiency and PD symptoms.

The cause of this cell death is poorly understood, but involves the build-up of misfolded α-synuclein proteins into Lewy bodies in the neurons. No curative treatment exists. Current treatment aims at replacing dopamine and reduce the effects of the symptoms. There is no cure for ALS today. The drugs riluzole (Rilutek®) and edavarone (Radicava®), approved in some regions, provide limited efficacy. Therefore, new agents halting or slowing down the disease process are desperately needed. Although this pharmacological treatment dramatically improves the quality of life of numerous PD patients, its therapeutic efficacy wanes over time leading to increase the doses and the number of daily intakes. Up to 50% of patients living with PD experience severe adverse events after several years of dopaminergic treatment, such as dyskinesia and ON/OFF fluctuation. Although there are alternative surgical treatments such as deep brain stimulation for approximately 10% of patients who display motor complications, all these treatments remain purely symptomatic and do not target the underlying neurodegenerative process. Thus, as the disease progresses, it becomes more and more debilitating and difficult to manage. Therefore, there is a significant unmet medical need for the development of novel neuroprotective and disease-modifying agents that will stop or slow down the dopaminergic neuron loss in this disease.