Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/NSAIDs

"There are strong indicators of positive neuroprotection from PD by NSAIDs in the following citations, but there are also some contra-indications."

Background
NSAIDs is an abbreviation of Nonsteroidal anti-inflammatory drugs. They are also referred to as nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal Anti-inflammatory medicines (NSAIMs). They are drugs with analgesic and antipyretic (fever-reducing) effects and which have, in higher doses, anti-inflammatory effects.

Common forms, which can be purchased over the counter in most countries, are aspirin, ibuprofen and nuproxen.

Research
1998

Aubin et al reported that The neurotoxic effects of the dopamine-selective neurotoxin MPTP (15 mg/kg, s.c.), in mice, were totally prevented by systemic administration of salicylate (ED50 = 40 mg/kg, i.p.), aspirin (ED50 = 60 mg/kg, i.p.), or the soluble lysine salt of aspirin, Aspegic (ED50 = 80 mg/kg, i.p.).

2000

Casper et al examined the effects of aspirin, acetaminophen, and ibuprofen on cultured primary rat embryonic neurons. All three NSAIDs significantly attenuated the decrease in dopamine uptake caused by glutamate, indicating preservation of neuronal integrity.

2003

Sairam et al evaluated the effect of NSAIDs on rats with induced (MPP+) Parkinsonism.

Celeoxib showed no effect. Diclofenac was effective only at high doses. Cyclooxygenase inhibitor significantly attenuated striatal DA depletion.

"The present study establishes potent neuroprotective activity of SA and suggests the use of aspirin in adjuvant therapy in Parkinson's disease."

Chen et al carried out an epidemiological study of 44,507 men and 98,845 women which included 415 cases of PD. They concluded that regular aspirin users had a lower risk of PD.

2005

Chen et al reviewed a large cohort of people and found that ibuprofen use may delay or prevent the onset of PD., but the same was not the case for aspirin or other NSAIDs.

2006

Ton et al evaluated a cohort of 206 PD cases and 383 controls. Their findings:-

"Our results provide only limited support for the hypothesis that use of aspirin may reduce the risk of this disease, and no indication of protection from other NSAIDs."

2007

Esposito et al reviewed the potential role of NSAIDs in the treatment of PD.

Wahner et al compared 293 PD cases with 286 controls and found:-

•	A decreased risk of PD among regular aspirin users. (especially women)

•	A stronger protective effect among non-aspirin NSAID users

2011

Gao et al reviewed a cohort of 136,197 people including 291 PD cases. They confirmed a reduced PD risk amongst regular users of ibuprofen but not among other NSAID users.

Driver et al made a study of a very large cohort and concluded:-

"This case-control study did not find evidence that NSAID use reduces Parkinson's disease risk"

Becker et al sought to resolve contradictions trown up by prevous studies into the neuroprotective potential of NSAIDs using a large health database. Their conclusions:-

"In this large observational study with data from the UK primary care, the long-term use of NSAIDs, aspirin, or acetaminophen was not associated with a substantially altered risk of developing PD."