Parkinson's Disease

Parkinson's disease (PD) is a long-term, progressive, neurodegenerative disease affecting approximately 1 million people in the US and generally occurring in people over 60 years of age. It is characterized by death of cells in the substantia nigra of the brain, leading to a reduction in levels of dopamine. Clinical symptoms include tremors, stiffness, and slow movement.

The precise cause of Parkinson's disease is unknown, although genetics and environmental exposures are implicated. Like many other neurodegenerative diseases, PD is thought to be a multi-factorial disease with many neurotoxins found in the brains of patients with the disease. Amongst these, the protein α-synuclein is considered a key protein and a target for drug development. However, also present at high levels are various forms of complement, iron accumulation, retrotransposons, gamma interferon, and reactive oxygen species. There is increasing evidence that these agents all contribute to the neuroinflammation that characterize PD.

All these neurotoxic elements, including α-synuclein, induce inflammasome activation, and markers of inflammasome activation (IL-1β, IL-18, and caspase-1) are elevated in the CSF of patients with Parkinson’s disease. Systemic levels of α-synuclein and markers of inflammasome activation are correlated with motor severity and progression of disease. 

While targeting a specific element (such as α-synuclein) may be successful, we believe that inflammasome activation, the common pathway for neuroinflammation that the various toxins cause, may be a more promising approach.   

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Parkinson’s disease affects approximately 1 million people in the US. The drugs used to treat it are designed to supplement dopamine levels and hence mask the symptoms but do not affect the progression of the disease. Unfortunately, as the disease progresses these drugs become less effective. The drugs used (formulations of L-DOPA and monoamine oxidase inhibitors) have been off-patent for many years and are relatively inexpensive. The total US drug sales for PD was $1.4B in 2020, while the annual direct cost of medical care for patients with PD exceeded $25B. A drug therapy that reduces or prevents the progression of the disease (and reduces overall care costs) would be extremely valuable.