Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment

Onesti, Emanuela; Frasca, Vittorio; Ceccanti, Marco; Tartaglia, Gian Gaetano; Gori, María; Cambieri, Chiara; Libonati, Laura; Palma, Eleonora; Inghilleri, Maurizio

doi:10.2174/1871527318666190131121827

Cited by 11 publications

(7 citation statements)

References 44 publications

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“…PEA has been reported to be effective in animal models of chronic pain and inflammation as well as in several clinical trials on various pain and inflammatory conditions. [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering from Migraine: A Pilot Study

Papetti

Sforza

Tullo

et al. 2020

Pain Research and Management

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Background. Palmitoylethanolamide (PEA) is emerging as a new therapeutic approach in pain and inflammatory conditions, and it has been evaluated in studies on various painful diseases. The aim of this open-label study was to evaluate the efficacy of ultramicronized PEA (umPEA) in the prophylactic treatment of migraine. Methods. The study included 70 patients with mean age of 10.3 ± 2.7 (24.5% M and 75.5% F). All patients had a diagnosis of migraine without aura (ICHD 3 criteria) and received umPEA (600 mg/day orally) for three months. We compared the attack frequency (AF) and attack intensity at baseline and after three months. Patients were asked to classify the intensity of the attack with a value ranging from 1 to 3, where 1 means mild attack, 2 moderate, and 3 severe attack. Results. Nine patients discontinued treatment before the target time of 12 weeks. After 3 months of treatment with umPEA, the headache frequency was reduced by >50% per month in 63.9% patients. The number of monthly attacks at T1 decreased significantly compared with the baseline assessment (from 13.9 ± 7.5 SD of T0 to 6.5 ± 5.9 SD of T1; p<0.001). The mean intensity of the attacks dropped from 1.67 ± 0.6 (T0) to 1.16 ± 0.5 (T1) (p<0.001), and the percentage of patients with severe attacks decreased after treatment (from 8.2% to 1.6%; p<0.05). The monthly assumptions of drugs for the attack reduced from 9.5 ± 4.4 to 4.9 ± 2.5 (p<0.001). Only one patient developed mild side effects (nausea and floating). Conclusions. Our preliminary data show that umPEA administered for three month reduces pain intensity and the number of attacks per month in pediatric patients with migraine. Although the small number of patients and the lack of control group do not allow us to consider these initial results as definitely reliable, they encourage us to expand the sample.

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Section: Introductionmentioning

confidence: 99%

Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering from Migraine: A Pilot Study

Papetti

Sforza

Tullo

et al. 2020

Pain Research and Management

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“…The pharmacological underpinnings of the likely changes in ACh after either OEA or PEA treatments were unknown, but current evidence hints at a possible role of both lipids in the modulation of ACh and 5‐HT through the engagement of PPARα (Donvito et al, 2017; Melis et al, 2008; Mennella et al, 2019). For instance, it has been demonstrated that activation of α7 nAChRs is associated to the promotion of OEA (Donvito et al, 2017) whereas PEA reduces the desensitization of ACh‐evoked currents (Onesti et al, 2019). However, findings regarding the role of OEA or PEA on ACh modulation are limited.…”

Section: Discussionmentioning

confidence: 99%

In vivo brain levels of acetylcholine and 5‐hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement

Murillo-Rodrı́guez

Arankowsky‐Sandoval

Budde

et al. 2021

Eur J of Neuroscience

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The peroxisome proliferator‐activated receptor alpha (PPARα) is a nuclear receptor that has been linked to the modulation of several physiological functions, including the sleep–wake cycle. The PPARα recognizes as endogenous ligands the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which in turn, if systemically injected, they exert wake‐promoting effects. Moreover, the activation of PPARα by the administration of OEA or PEA increases the extracellular contents of neurotransmitters linked to the control of wakefulness; however, the role of PPARα activated by OEA or PEA on additional biochemicals related to waking regulation, such as acetylcholine (ACh) and 5‐hydroxytryptamine (5‐HT), has not been fully studied. Here, we have investigated the effects of treatments of OEA or PEA on the contents of ACh and 5‐HT by using in vivo microdialysis techniques coupled to HPLC means. For this purpose, OEA or PEA were systemically injected (5, 10 or 30 mg/kg; i.p.), and the levels of ACh and 5‐HT were collected from the basal forebrain, a wake‐related brain area. These pharmacological treatments significantly increased the contents of ACh and 5‐HT as determined by HPLC procedures. Interestingly, PPARα antagonist MK‐886 (30 mg/kg; i.p.) injected before the treatments of OEA or PEA blocked these outcomes. Our data suggest that the activation of PPARα by OEA or PEA produces significant changes on ACh and 5‐HT levels measured from the basal forebrain and support the conclusion that PPARα is a suitable molecular element involved in the regulation of wake‐related neurotransmitters.

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“…Since these positive effects appeared after only one week of treatment, it is not surprising that they disappeared one week after the withdrawal of the ultra-micronized PEA. Notably, the antibody titre did not significantly change following PEA treatment [ 101 ], suggesting a possible direct effect of ultra-micronized PEA on nAChRs as already shown in ALS patients. The capacity of PEA to reduce the release of pro-inflammatory cytokines could also be exploited to treat diseases such as sarcopenia, a condition characterized by progressive and generalized loss of skeletal muscle mass and strength combined with low physical performance [ 103 ].…”

Section: Pea In Neuromuscular Alterations and Diseasesmentioning

confidence: 99%

“…Taken together, data obtained from this study showed that PEA add-on therapy slows the disease progression, suggesting that PEA could represent a valid aid to slow respiratory impairment in these patients, thus increasing their life expectancy. In another open-label pilot study, also carried out by Inghilleri’s group at the Policlinico Umberto I in Rome, oral ultra-micronized PEA was administered to a cohort of patients afflicted by myasthenia gravis (MG) [ 101 ]. This autoimmune disease is characterized by the presence of auto-antibodies able to disrupt the physiological function of NMJ.…”

Section: Pea In Neuromuscular Alterations and Diseasesmentioning

confidence: 99%

“…The progression of the disease can be sneaky, with long periods of spontaneous remission or rapid progression [ 102 ]. In the aforementioned study [ 101 ], after only one week of treatment, patients displayed a significant improvement of all the neurophysiological parameters taken in account. In detail, ultra-micronized PEA induced a statistically significant improvement of the quantitative myasthenia gravis score (QMG), thus reducing the level of disability of the treated patients, and also a significant effect in improving the pathological muscle responses (measured as “decremental muscle responses”, RNS).…”

Section: Pea In Neuromuscular Alterations and Diseasesmentioning

confidence: 99%

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Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function

et al. 2022

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Recently, the endocannabinoid system has attracted growing attention from the scientific community for its involvement in homeostatic and pathological processes as they pertains to human physiology. Among the constituents of the endocannabinoid system, the molecule palmitoyl ethanolamide has particularly been studied for its ability to reduce several inflammatory processes involving the central nervous system. Here, we reviewed published literature and summarized the main targets of the palmitoyl ethanolamide, along with its unique possible mechanisms for restoring correct functioning of the central nervous system. Moreover, we have highlighted a less-known characteristic of palmitoyl ethanolamide, namely its ability to modulate the function of the neuromuscular junction by binding to acetylcholine receptors in different experimental conditions. Indeed, there are several studies that have highlighted how ultra-micronized palmitoyl ethanolamide is an interesting nutraceutical support for the treatment of pathological neuromuscular conditions, specifically when the normal activity of the acetylcholine receptor is altered. Although further multicentric clinical trials are needed to confirm the efficacy of ultra-micronized palmitoyl ethanolamide in improving symptoms of neuromuscular diseases, all the literature reviewed here strongly supports the ability of this endocannabinoid-like molecule to modulate the acetylcholine receptors thus resulting as a valid support for the treatment of human neuromuscular diseases.

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Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment

Cited by 11 publications

References 44 publications

Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering from Migraine: A Pilot Study

Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering from Migraine: A Pilot Study

In vivo brain levels of acetylcholine and 5‐hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement

Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function

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