Tag: Moreau

SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis

Abstract:

Background: Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is emerging as a potential biomarker and therapeutic target in myalgic encephalomyelitis (ME), a complex multisystem disorder characterized by immune dysfunction, metabolic disturbances, and persistent fatigue. This study investigates the role of SMPDL3B in ME pathophysiology and explores its clinical relevance.

Methods: A case-control study was conducted in two independent cohorts: a Canadian cohort (249 ME patients, 63 controls) and a Norwegian replication cohort (141 ME patients). Plasma and membrane-bound SMPDL3B levels were quantified using ELISA and flow cytometry. Gene expression of SMPDL3B and PLCXD1, encoding phosphatidylinositol-specific phospholipase C (PI-PLC), was analyzed by qPCR. The effects of dipeptidyl peptidase-4 (DPP-4) inhibitors-vildagliptin, saxagliptin, and linagliptin-on modulation of membrane-bound and soluble SMPDL3B were assessed in vitro by qPCR, flow cytometry and ELISA.

Results: ME patients exhibited significantly elevated plasma SMPDL3B levels, which correlated with symptom severity. Flow cytometry revealed a reduction in membrane-bound SMPDL3B in monocytes, accompanied by increased PLCXD1 expression and elevated plasma levels of PI-PLC and SMPDL3B. These findings suggest that immune dysregulation in ME may be linked to enhanced cleavage of membrane-bound SMPDL3B by PI-PLC. Sex-specific differences were observed, with female ME patients displaying higher plasma SMPDL3B levels, an effect influenced by estrogen. In vitro, estradiol upregulated SMPDL3B expression, indicating hormonal regulation. Vildagliptin and saxagliptin were tested for their potential to inhibit PI-PLC activity independently of their role as DPP-4 inhibitors, and restored membrane-bound SMPDL3B while reduced its soluble form.

Conclusions: SMPDL3B emerges as a key biomarker for ME severity and immune dysregulation, with its activity influenced by hormonal and PI-PLC regulation. The ability of vildagliptin and saxagliptin to preserve membrane-bound SMPDL3B and reduce its soluble form via PI-PLC inhibition suggests a novel therapeutic strategy. These findings warrant clinical trials to evaluate their potential in mitigating immune dysfunction and symptom burden in ME.

Note: See Correction: SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis

Source: Rostami-Afshari B, Elremaly W, Franco A, Elbakry M, Akoume MY, Boufaied I, Moezzi A, Leveau C, Rompré P, Godbout C, Mella O, Fluge Ø, Moreau A. SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis. J Transl Med. 2025 Jul 7;23(1):748. doi: 10.1186/s12967-025-06829-0. PMID: 40624584; PMCID: PMC12236014. https://pmc.ncbi.nlm.nih.gov/articles/PMC12236014/ (Full text)

Exploring the neurocognitive consequences of post-exertional malaise in myalgic encephalomyelitis

Background and aims:

Myalgic encephalomyelitis (ME) is a complex, debilitating and heterogeneous disorder. It affects over 500,000 people in Canada but remains poorly understood. People are affected with multi-systemic symptoms such as fatigue that is not alleviated by rest, pain, cognitive impairment and post-exertional malaise (PEM), which is considered as the hallmark symptom of ME. PEM is triggered by minimal mental or physical effort and exacerbates other symptoms. Our aim was to measure how individuals’ cognition can be impacted by the induction of PEM, and investigate the difference in cognitive response.

Section snippets:

Methods
A prospective cohort of people with ME (n = 42) and matched healthy controls (n = 15) was recruited and subjected to PEM induction through a 90-minutes mechanical arm stimulation. BrainCheck test (BrainCheck, Inc., TX, USA) was used at baseline (T0) and after 90 minutes of stimulation to evaluate six cognitive domains for which each participant received a score and a population percentile based on their performance.

Results
Comparison between both groups was significant (p < 0.05) at T90, but not at T0, in four out of six cognitive domains. We then classified our ME cohort in three clusters by k-means method based on the Δ percentile (T90-T0) for each cognitive task. This stratification allowed us to notice how some cognitive domains seem more affected depending on the cluster, namely memory and attention.

Conclusions
These results showed the impact of PEM on the disturbance of cognition in the context of ME as well as the variability of cognitive domains affected in people with ME.

Source: Corinne Leveau, Iurie Caraus, Anita Franco, Alain Moreau. Exploring the neurocognitive consequences of post-exertional malaise in myalgic encephalomyelitis. Journal of the Neurological Sciences, Volume 455, Supplement, December 2023, 122590. https://www.sciencedirect.com/science/article/abs/pii/S0022510X23020518

 

Circulating microRNA expression signatures accurately discriminate myalgic encephalomyelitis from fibromyalgia and comorbid conditions

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and fibromyalgia (FM) are two chronic complex diseases with overlapping symptoms affecting multiple systems and organs over time. Due to the absence of validated biomarkers and similarity in symptoms, both disorders are misdiagnosed, and the comorbidity of the two is often unrecognized.

Our study aimed to investigate the expression profiles of 11 circulating miRNAs previously associated with ME/CFS pathogenesis in FM patients and individuals with a comorbid diagnosis of FM associated with ME/CFS (ME/CFS + FM), and matched sedentary healthy controls. Whether these 11 circulating miRNAs expression can differentiate between the two disorders was also examined.

Our results highlight differential circulating miRNAs expression signatures between ME/CFS, FM and ME/CFS + FM, which also correlate to symptom severity between ME/CFS and ME/CFS + FM groups. We provided a prediction model, by using a machine-learning approach based on 11 circulating miRNAs levels, which can be used to discriminate between patients suffering from ME/CFS, FM and ME/CFS + FM. These 11 miRNAs are proposed as potential biomarkers for discriminating ME/CFS from FM.

The results of this study demonstrate that ME/CFS and FM are two distinct illnesses, and we highlight the comorbidity between the two conditions. Proper diagnosis of patients suffering from ME/CFS, FM or ME/CFS + FM is crucial to elucidate the pathophysiology of both diseases, determine preventive measures, and establish more effective treatments.

Source: Nepotchatykh E, Caraus I, Elremaly W, Leveau C, Elbakry M, Godbout C, Rostami-Afshari B, Petre D, Khatami N, Franco A, Moreau A. Circulating microRNA expression signatures accurately discriminate myalgic encephalomyelitis from fibromyalgia and comorbid conditions. Sci Rep. 2023 Feb 2;13(1):1896. doi: 10.1038/s41598-023-28955-9. PMID: 36732593. https://www.nature.com/articles/s41598-023-28955-9 (Full text)