Author Of 4 Presentations
P0517 - Circulating miRNA signatures in PPMS (ID 1309)
Primary progressive multiple sclerosis (PPMS) is a clinical subtype of MS characterized by the progressive accumulation of disability from onset. It is diagnosed in approximately 15% of people with multiple sclerosis (MS).
microRNAs (miRNAs) are small non-coding RNA molecules that participate in the regulation of gene expression. Their role in different diseases, including MS, is being studied.
Current disease-modifying therapies for MS as well as miRNA studies mainly focus on relapsing-remitting MS (RRMS), the most common subtype.
The aim of this study was to identify and validate a differential profile of circulating miRNAs in PPMS patients compared to RRMS and controls with other neurological disease (OND) subjects in order to increase our knowledge of the biological processes involved in the different forms of the disease.
miRNAs were extracted from serum and cerebrospinal fluid (CSF) from a cohort of 111 patients (49 PPMS, 35 RRMS and 27 OND). In the identification phase, samples were analyzed using TaqMan OpenArray Human Advanced MicroRNA panels and in the validation phase, the quantification of the miRNAs was performed by qPCR. Differential expression was analyzed using the Kruskal-Wallis test with the normalized value of miRNAs.
In the identification phase, 10 miRNAs showed differential expression in serum between some of the groups; while in CSF, miR-143-3p presented differential expression in PPMS group (p= 0.009), and let-7b-5p and miR-451a showed a tendency to be deregulated.
In serum samples, the validation phase showed miR-20a-5p overexpression in PPMS compared to controls, and miR-26a-5p among the forms of MS (p= 0.002 and p= 0.036, respectively). On the other hand, miR-142-5p was differentially expressed in RRMS compared to OND (p= 0.036).
In CSF, let-7b-5p and miR-143-3p presented significantly reduced levels in PPMS forms compared to OND (p= 0.029 and p= 0.039, respectively).
miR-20a-5p, miR-26a-5p, let-7b-5p and miR-143-3p present deregulation in PPMS versus RRMS and OND, indicating that they are involved in the pathophysiological mechanisms of PPMS forms. Further studies will be necessary to determine the role of these miRNAs in the development of the different forms of the disease.
P0519 - Differential expression of miRNAs in CSF of MS patients depending on their ethnic origin (ID 1312)
Some studies have shown a more aggressive clinical course in multiple sclerosis (MS) patients of North African origin residing in Europe. It has been established that some genetic and environmental factors interact in a complex way by means of epigenetics to produce the pathology and the symptoms in MS. One of these epigenetic mechanisms is microRNAs (miRNAs), small non-coding RNA molecules that participate in the regulation of gene expression.
The objective of this study was to identify the existence of a differential profile of circulating cerebrospinal fluid (CSF) miRNAs between individuals with MS based on their ethnic origin.
A cohort of 20 individuals was studied: 10 European origin (MS-E) and 10 North African origin individuals (MS-NA). MS-NA individuals were subclassified according to migration age (before or after 15 years old).
216 miRNAs were analyzed in CSF using TaqMan OpenArray Human Advanced MicroRNA panels. Differential expression of the normalized value of each miRNA was studied using the U Mann-Whitney test.
When comparing the expression of miRNAs in CSF between MS-E and MS-NA, overexpression of miR-335-5p and miR-653-3p was observed in MS-NA (p= 0.008 and p= 0.027, respectively). Furthermore, two other miRNAs (miR-143-3p and miR-20a-5p) showed a tendency to be deregulated.
A sub-analysis was performed in which MS-NA was divided according to the age of migration. miR-145-5p, miR-150-5p and miR-653-3p showed significant differences between some of the 3 groups. Specifically, miR-150-5p, previously related to inflammation and MS in CSF, showed very low levels in MS-NA that migrated older than 15 years of age.
The results show the presence of a differential expression in miRNAs between MS patients according to their ethnic origin. In patients of North African origin who migrated at an early age, an overexpression of miRNAs clearly related to inflammation is observed.
P0524 - Importance of control group selection for differential miRNA profile studies (ID 1296)
Cerebrospinal fluid (CSF) studies are necessary in neurological diseases, but the use of healthy controls (HC) is limited due to the ethical issues and difficulty in obtaining them. Usually, the control group corresponds to patients with other neurological diseases (OND).
The main objective of this study was to evaluate the role of the control group in detecting altered miRNAs in multiple sclerosis (MS).
A panel of 216 CSF-specific miRNAs were analyzed using TaqMan Open Array Human Advanced MicroRNA in a cohort of 38 patients (16 primary progressive forms – PPMS, 9 HC, 13 OND).
HC corresponds to neurologically healthy patients with hip/knee impairment undergoing surgical intervention that requires spinal anaesthesia.
The pathologies presented by OND were: 6 individuals of vascular origin, 3 migraines, 1 conversion syndrome, 1 dementia, 1 dizziness, 1 cerebellar syndrome of non-inflammatory/infectious origin.
miR-1260a, miR-320a, and let-7c-5p showed differential expression, or a trend, in PPMS versus HC (p = 0.005; p = 0.021; p = 0.088, respectively). When making the same comparison with OND these significances were lost.
When analyzing deregulated miRNAs function, it was observed that let-7c-5p and miR-320a are involved in cerebral ischaemic and neurodegenerative disorders.
Choosing the control group is crucial to identify altered miRNAs in a specific condition. If the objective is to identify metabolic pathways involved in a certain process, HC will be necessary since OND controls can share the altered pathways. On the other hand, when the objective is to identify biomarkers, the incorporation of OND into the analysis will be of great value to differentiate pathologies.
P0873 - Experience with teriflunomide in a specialized multiple sclerosis unit (ID 1393)
There are different treatments used for multiple sclerosis. Observational data generates evidence about what are the efficacy, safety, tolerance, adherence and management of these drugs in real world.
To describe the experience with the use of teriflunomide in a specialized multiple sclerosis (MS) unit from September 2015 to May 2020
Epidemiological analysis of MS patients treated with teriflunomide from September 2015 to May 2020 in a specialized MS unit, together with the reasons to start and to stop with the treatment and the clinical evolution of the patients.
112 patients (70% women, 30% men) were treated with teriflunomide from September 2015 to May 2020. The mean age was 42 years (range 21-68 years). Teriflunomide was the first MS treatment in >50% of cases and the others had been treated with other MS treatments with moderate efficacy, mainly interferons and glatiramer acetate. During this period, the drug was discontinued in 38 patients (34%): 27 patients for disease activity (relapses or new brain o spinal core lesions), 5 for adverse events, 4 for developing a progressive form of the disease, 2 for pregnancy desire, 1 for personal decision. There have been no severe adverse events. 3 patients had severe diarrhea and 2 peripheral neuropathy. 5 patients had significant hair fragility that was treated but did not cause discontinuation of teriflunomide.
Teriflunomide is an optimal, suitable and effective drug for relapsing-remitting with known and mild-to-moderate adverse events.