Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis

Romero, María José Zarzuelo; Ramírez, Cristina Pérez; Campos, Maria Isabel Carrasco; Martín, Ángel Puerto; Hernández, Miguel Ángel Calleja; Tortosa, María Carmen Ramírez; Morales, Alberto Jiménez

doi:10.3390/jpm11050335

Cited by 13 publications

(11 citation statements)

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“…However, other variants have been studied in the context of response to DMF and fingolimod. Rs6919626, in NADPH oxidase-3 gene, has been significantly associated with a lower response to DMF, but no significant associations have been found with the response to fingolimod yet ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A pharmacogenomics Egyptian study

Amin

El-Aziz²,

Hamed³

et al. 2023

Front. Immunol.

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BackgroundMultiple sclerosis (MS) is characterized by a complex etiology that is reflected in the lack of consistently predictable treatment responses across patients of seemingly similar characteristics. Approaches to demystify the underlying predictors of aberrant treatment responses have made use of genome-wide association studies (GWAS), with imminent progress made in identifying single nucleotide polymorphisms (SNPs) associated with MS risk, disease progression, and treatment response. Ultimately, such pharmacogenomic studies aim to utilize the approach of personalized medicine to maximize patient benefit and minimize rate of disease progression.ObjectiveVery limited research is available around the long intergenic non-coding RNA (linc)00513, recently being reported as a novel positive regulator of the type-1 interferon (IFN) pathway, following its overexpression in the presence of two polymorphisms: rs205764 and rs547311 in the promoter region of this gene. We attempt to provide data on the prevalence of genetic variations at rs205764 and rs547311 in Egyptian MS patients, and correlate these polymorphisms with the patients’ responses to disease-modifying treatments.MethodsGenomic DNA from 144 RRMS patients was isolated and analyzed for genotypes at the positions of interest on linc00513 using RT-qPCR. Genotype groups were compared with regards to their response to treatment; additional secondary clinical parameters including the estimated disability status score (EDSS), and onset of the disease were examined in relation to these polymorphisms.ResultsPolymorphisms at rs205764 were associated with a significantly higher response to fingolimod and a significantly lower response to dimethylfumarate. Moreover, the average EDSS of patients carrying polymorphisms at rs547311 was significantly higher, whereas no correlation appeared to exist with the onset of MS.ConclusionUnderstanding the complex interplay of factors influencing treatment response is pivotal in MS. One of the factors contributing to a patient’s response to treatment, as well as disease disability, may be polymorphisms on non-coding genetic material, such as rs205764 and rs547311 on linc00513. Through this work, we propose that genetic polymorphisms may partially drive disease disability and inconsistent responses to treatment in MS; we also aim to draw attention towards genetic approaches, such as screening for specific polymorphisms, to possibly direct treatment choices in such a complex disease.

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Section: Discussionmentioning

confidence: 99%

Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A pharmacogenomics Egyptian study

Amin

El-Aziz²,

Hamed³

et al. 2023

Front. Immunol.

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“…Single nucleotide polymorphisms in the CYP2C9 gene affect an individual's ability to metabolize this drug, influencing its plasmatic levels and therefore safety, but not effectiveness. 32 The approved label mandates CYP2C9 genotyping prior to initiation of siponimod. For patients carrying a CYP2C9 Ã 3/ Ã 3 genotype (around 0.3% to 0.4% of Caucasians and less in other ethnic groups) the drug is formally contraindicated, whereas for those with the CYP2C9 Ã 1/ Ã 3 and CYP2C9 Ã 2/ Ã 3 genotypes the daily maintenance dose must be 1 mg instead of 2 mg. 32 Other polymorphisms in the CYP2C9 are under investigation regarding their influence on the safety of siponimod.…”

Section: Pharmacogenomics To Predict Safety and Efficacymentioning

confidence: 99%

Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine

dos Passos,

Adoni,

Mendes

et al. 2023

Arq Neuropsiquiatr

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Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding of the factors leading to heterogeneity within the same disease, development of targeted therapies, and strategies to tailor therapies to each patient. This review explores the impact of precision medicine on various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, and immune-mediated neuropathies. We discuss advances in disease subtyping, recognition of novel entities, promising biomarkers, and the development of more selective monoclonal antibodies and cutting-edge synthetic cell-based immunotherapies in neuroimmunological disorders. In addition, we analyze the challenges related to affordability and equity in the implementation of these emerging technologies, especially in situations with limited resources.

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“…Pharmacogenetics is the study of how genetic variants influence drug response [ 35 , 36 , 37 , 38 ]. The use of GA as one of the first-line treatments for MS has significantly improved outcomes but has also shown great variability in response among patients [ 39 , 40 , 41 , 42 ].…”

Section: Pharmacogenetics Of Glatiramer Acetate In Msmentioning

confidence: 99%

Influence of Genetic Polymorphisms on Clinical Outcomes of Glatiramer Acetate in Multiple Sclerosis Patients

Zarzuelo

Pérez-Ramírez

Cura

et al. 2021

JPM

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Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. Treatment is aimed at slowing down the course of the disease and mitigating its symptoms. One of the first-line treatments used in patients with MS is glatiramer acetate (GA). However, in clinical practice, a response rate of between 30% and 55% is observed. This variability in the effectiveness of the medication may be influenced by genetic factors such as polymorphisms in the genes involved in the pathogenesis of MS. Therefore, this review assesses the impact of genetic variants on the response to GA therapy in patients diagnosed with MS. The results suggest that a relationship exists between the effectiveness of the treatment with GA and the presence of polymorphisms in the following genes: CD86, CLEC16A, CTSS, EOMES, MBP, FAS, TRBC1, IL1R1, IL12RB2, IL22RA2, PTPRT, PVT1, ALOX5AP, MAGI2, ZAK, RFPL3, UVRAG, SLC1A4, and HLA-DRB1*1501. Consequently, the identification of polymorphisms in these genes can be used in the future as a predictive marker of the response to GA treatment in patients diagnosed with MS. Nevertheless, there is a lack of evidence for this and more validation studies need to be conducted to apply this information to clinical practice.

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Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis

Cited by 13 publications

References 100 publications

Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A pharmacogenomics Egyptian study

Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A pharmacogenomics Egyptian study

Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine

Influence of Genetic Polymorphisms on Clinical Outcomes of Glatiramer Acetate in Multiple Sclerosis Patients

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