um-Palmitoylethanolamide can slow down Parkinson’s disease


Parkinson disease (PD) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. First described by the English physician James Parkinson two centuries ago, there is yet no cure for PD. Indeed, there is a long list of failed clinical studies based on successful data obtained with exogenous neurotoxin preclinical models [1]. Palmitoylethanolamide, an endogenous fatty acid amide signalling molecule well-known for its ability to promote the resolution of neuroinflammation and exert neuroprotection, has shown potential therapeutic action in such animal models [2,3]. In our research, we show that ultra-micronized palmitoylethanolamide (um-PEA), slows down disease progression and disability when used as add-on therapy in advanced PD patients.

30 patients with diagnosed PD (mean age of 73) receiving L-DOPA daily and other PD medications in some cases were assessed monthly over 3 consecutive months. Thereafter, um-PEA (Normast®, a food for special medical purposes) was given at 1200 mg daily for 3 months, followed by 600 mg/day for up to 12 months. The MDS-UPDRS questionnaire was used to assess motor and non-motor symptoms. Patients underwent clinical assessment at months 1, 3, 6 and 12. PD medications were maintained during the period of um-PEA treatment.

um-PEA add-on therapy to L-DOPA led a significant and progressive reduction of total score in Non-Motor Aspects of Experiences of Daily Living, decreasing from 9.7 ± 1.18 at baseline to 4.5 ± 0.69 at month 12.

Moreover, one year um-PEA adjuvant therapy brought about a significant and progressive reduction in the average Motor Aspects of Experiences of Daily Living total score, from 12.7 ± 1.37 at baseline to 7.6 ± 1.06 at month 12.

In addition, average total motor complication score diminished from 8.8 ± 0.8 at baseline to 4.2 ± 0.48 after 12 months of um-PEA adjuvant therapy.

The addition of um-PEA treatment also induced a significant and progressive reduction of motor complications that went from 8.8 ± 0.8 at baseline to 4.2 ± 0.48 at the end of um-PEA therapy.

None of the participants reported side effects attributable to um-PEA.

In conclusion, um-PEA represents a safe and efficacious adjuvant treatment in patients with advanced PD receiving L-DOPA therapy, by providing clinically meaningful improvements in non-motor and motor aspects of daily living, as well as motor symptoms and motor complications of the disease. Moreover, our findings demonstrate the translatability of um-PEA action in PD from rodent to man.


Stefania Brotini1, Carlo Schievano2, and Leonello Guidi3

1,3Movement Disorder Center, Department of Neurology, San Giuseppe Hospital, Empoli, Florence, Italy.

2Department of Statistical Sciences, University of Padua, Italy; Innovative statistical Statistical Research, Padua, Italy

Reference: Brotini S. et al. (2017).

Ultra-Micronized Palmitoylethanolamide: An Efficacious Adjuvant Therapy for Parkinson Disease, CNS Neurol Disord Drug Targets, doi: 10.2174/1871527316666170321124949.

[1] Athauda D, Foltynie T. The ongoing pursuit of neuroprotective therapies in Parkinson disease, Nat Rev Neurol (2015);11:25-40.

[2] Avagliano C, Russo R, De Caro C, Cristiano C, La Rana G, Piegari G, et al. Palmitoylethanolamide protects mice against 6-OHDA-induced neurotoxicity and endoplasmic reticulum stress: in vivo and in vitro evidence, Pharmacol Res (2016);113:276-89.

[3] Esposito E, Impellizzeri D, Mazzon E, Paterniti I, Cuzzocrea S. Neuroprotective activities of palmitoylethanolamide in an animal model of Parkinson's disease. PLoS One (2012);7:e41880. doi: 10.1371/journal.pone.0041880.

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