Percorrer por autor "Teixeira, Catarina"
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- Circulating miR-134 in mesial temporal lobe epilepsy: implications in hippocampal sclerosis development and drug resistancePublication . Guerra Leal, Bárbara; Carvalho, Cláudia; Santos, Cristina; Samões, Raquel; Martins-Ferreira, Ricardo; Teixeira, Catarina; Rodrigues, Diana; Freitas, Joel; Lemos, Carolina; Chorão, Rui; Ramalheira, João; Lopes, João; Martins da Silva, António; Pinho E Costa, Paulo; Chaves, JoãoAim: miR-134 has been widely reported as upregulated in experimental and human studies of Mesial Temporal Lobe Epilepsy the most common drug-resistant epilepsy (DRE). Studies have shown that the use of antagomirs, anti-miR-134, may be a promising therapeutic approach to these epilepsies. However, data on miR-134 in other epileptic syndromes is scarce. In this study, we aimed to quantify serum levels of miR-134 in a cohort of patients with Mesial Temporal Lobe Epilepsy-Hippocampal Sclerosis (MTLE-HS) and with Genetic Generalized Epilepsies (GGE). Additionally, we explored the correlation between miR-134 serum levels and clinical parameters, such as age at onset or febrile seizures antecedents, to evaluate its potential as a biomarker and therapeutic target in epilepsy. Methods: miR-134 levels were evaluated in cell-free serum of 131 patients with epilepsy (75 women, 56 men; age 41.10 ± 13.12 years; 72 with DRE) and 42 healthy individuals (25 women, 17 men; age 42.40 ± 9.80 years). The epilepsy cohort included 77 MTLE-HS patients and 54 GGE patients. Results: Patients with elevated miR-134 circulating levels were at higher risk of drug-resistant epilepsy (OR [95% CI] = 2.246 [1.111–4.539], p = 0.021). Other risk factors included an older age (OR [95% CI] = 1.032 [1.004–1.061], p = 0.025), history of febrile seizures (OR [95% CI] = 2.994 [1.385–6.471], p = 0.005) and higher disease duration (OR [95% CI] = 1.038 [1.011–1.066], p = 0.006). The strongest predictor of DRE was hippocampal sclerosis (OR [95% CI] = 10.338 [4.566–23.404], p < 0.001). Circulating miR-134 levels were significantly higher in MTLE-HS patients compared to controls (p < 0.05) and GGE patients (p < 0.05). However, the clinical utility of miR-134 in discriminating MTLE-HS patients from controls was only moderated (AUC = 0.651 ± 0.051 95% CI 0.551–0.751, p = 0.007). Conclusion: We show that miR-134 circulating levels are associated with DRE, especially in MTLE-HS, a syndrome characterized by severe hippocampal damage, consistent with activity-regulated miR-134 expression. This overexpression likely contributes to disease progression and our results support the potential of targeting miR-134 as a novel therapeutic approach for refractory epilepsy.
- MicroRNAs as potential biomarkers of response to modified Atkins diet in treatment of adults with drug-resistant epilepsy: A proof-of-concept studyPublication . Samões, Raquel; Cavalheiro, Ana; Santos, Cristina; Lopes, Joana; Teixeira, Catarina; Tavares, Maria Manuel; Carvalho, Cláudia; Lemos, Carolina; Costa, Paulo Pinho e; Cavaco, Sara; Chaves, João; Leal, BárbaraBackground: Accurate predictors of response to modified Atkins diet (MAD) are needed. MicroRNAs are potential biomarkers in epilepsy. This study aimed to explore the value of circulating miR-146a, miR-155, miR-22, miR-21 and miR-134 levels in predicting response to MAD. Methods: Patients who completed 3 months of MAD were selected from a prospective cohort of adults with DRE followed in a specialized MAD outpatient clinic. Patients were classified as responders if any reduction in seizure frequency at follow-up, calculated through seizure-calendars). The >50 % seizure reduction cut-off was also explored. Qualitative benefits in seizures and cognition were analysed. Blood samples were collected prior to initiate MAD and microRNAs were quantified by qRT-PCR. Results: Thirty-nine patients were included (56 %males, mean age=33.1±8.5yo, 62 %focal epilepsies, 59 %structural aetiology): 20(51 %) were responders [mean reduction in seizure frequency=54 %(17-100 %); 10 had ≥50 % reduction]; 25(64 %) reported qualitative benefit in seizures and 21(54 %) reported cognitive benefits. At pre-treatment baseline, a panel combining serum levels of all studied microRNAs predicted seizure reduction (AUC=0.839, p<0.0001), qualitative benefit in seizures (AUC=0.683, p=0.048) and in cognition (AUC=0.751, p<0.01) at 3months. miR-146a was the only significant microRNA when evaluated in isolation. There was no statistical correlation in the biomarkers when a ≥50 % seizure reduction was compared to <50 %. Conclusions: A panel combining pre-treatment serum levels of miR-146a, miR-155, miR-134, miR-21 and miR-22 predicted any reduction in seizures with MAD in adults with DRE at 3months. This panel may be a promising biomarker and a useful tool in the selection of patients.