Marc Gotkine
A5037794740- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Acute Ischemic Stroke Management
- Peripheral Neuropathies and Disorders
- Genetic Neurodegenerative Diseases
- Migraine and Headache Studies
- Muscle Physiology and Disorders
- Multiple Sclerosis Research Studies
- Myasthenia Gravis and Thymoma
- Epigenetics and DNA Methylation
- Cerebrovascular and Carotid Artery Diseases
- Cervical and Thoracic Myelopathy
- Ophthalmology and Eye Disorders
- Vasculitis and related conditions
- Long-Term Effects of COVID-19
- Hereditary Neurological Disorders
- Intracerebral and Subarachnoid Hemorrhage Research
- Neurosurgical Procedures and Complications
- Cellular transport and secretion
- Systemic Lupus Erythematosus Research
- Moyamoya disease diagnosis and treatment
- Cancer-related gene regulation
Hadassah Medical Center
2016-2025
Hebrew University of Jerusalem
2012-2025
Hôpital Pierre Wertheimer
2025
Hospices Civils de Lyon
2025
Inserm
2010-2025
Centre National de la Recherche Scientifique
2025
Université Claude Bernard Lyon 1
2025
Centre de Recherche en Neurosciences de Lyon
2025
Centre Hospitalier Saint-Nazaire
2019-2023
Fondazione Santa Lucia
2022
Variants of UNC13A, a critical gene for synapse function, increase the risk amyotrophic lateral sclerosis and frontotemporal dementia
<h3>Importance</h3> Preclinical studies have shown that neurotrophic growth factors (NTFs) extend the survival of motor neurons in amyotrophic lateral sclerosis (ALS) and combined delivery these has a strong synergistic effect. We developed culture-based method for inducing mesenchymal stem cells (MSCs) to secrete factors. These MSC-NTF been be protective several animal models neurodegenerative diseases. <h3>Objective</h3> To determine safety possible clinical efficacy autologous...
Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes...
Background Despite several studies suggesting a potential oligogenic risk model in amyotrophic lateral sclerosis (ALS), case–control statistical evidence implicating oligogenicity with disease or clinical outcomes is limited. Considering its direct and therapeutic implications, we aim to perform large-scale robust investigation of ALS the course. Methods We leveraged Project MinE genome sequencing datasets (6711 cases 2391 controls) identify associations between known genes risk, as well...
Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age symptom onset less than 25 years and variable presentation.
Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death organs affected by cancer be detected tissue-specific methylation patterns of circulating cell-free DNA (cfDNA). We elevated levels hepatocyte-derived cfDNA the plasma patients with liver metastases originating from different primary tumors, compared without metastases. In addition, localized pancreatic or colon showed hepatocyte cfDNA, suggesting inflicted...
With the advent of gene therapies for amyotrophic lateral sclerosis (ALS), there is a surge in testing this disease. Although ample experience with C9orf72, SOD1, FUS and TARDBP familial ALS, large studies exploring genetic variation all ALS-associated genes sporadic ALS (sALS) are still scarce. Gene diagnostic setting challenging, given complex architecture sALS, which variants small effect sizes. Guidelines interpretation panels counselling patients lacking. We aimed to provide thorough...
TDP-43 (TAR DNA-binding protein 43) aggregation and redistribution are recognised as a hallmark of amyotrophic lateral sclerosis frontotemporal dementia. As inclusions have recently been described in the muscle inclusion body myositis patients, this highlights need to understand role beyond central nervous system. Using RNA-seq, we directly compare TDP-43-mediated RNA processing (C2C12) neuronal (NSC34) mouse cells. displays cell-type-characteristic behaviour targeting unique transcripts...
Abstract There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up 60%. Both Mendelian and small effect variants have been identified, but in common other conditions, such only explain little the heritability. Genomic structural variation might account for some this otherwise unexplained We therefore investigated association between set 25 ALS genes, risk phenotype. As expected, repeat expansion C9orf72 gene was identified as...
Abstract Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome. In up to 20% of cases, family history observed. Although Mendelian disease gene variants are found in apparently sporadic ALS, genetic testing usually restricted those with or younger patients disease. With the advent therapies targeting it important that everyone treatable identified. We therefore sought determine probability clinically actionable ALS test result by age onset, globally, but using UK...
Abstract Background Malfunction of astrocytes is implicated as one the pathological factors ALS. Thus, intrathecal injection healthy in ALS can potentially compensate for diseased astrocytes. AstroRx® an allogeneic cell-based product, composed and functional human derived from embryonic stem cells. was shown to clear excessive glutamate, reduce oxidative stress, secrete various neuroprotective factors, act immunomodulator. Intrathecal animal models slowed disease progression extended...
Abstract Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they abundant myelin membranes. Serine palmitoyltransferase, enzyme that catalyses rate-limiting reaction sphingolipid synthesis, is composed multiple subunits including an activating subunit, SPTSSA. both essential cytotoxic their synthesis must therefore be tightly regulated. Key to homeostatic regulation ORMDL proteins bound serine...
Carotid artery dissection (CAD) is a common cause of stroke in young patients. Clots formed at the low-flow zone false arterial lumen may give rise to distal emboli, and mural hematoma eventually occlude artery. Anticoagulation currently accepted treatment, but it unknown which patients will improve spontaneously, respond anticoagulation, have an exacerbation ischemic symptoms despite therapy. Endovascular treatment CAD be attractive alternative methods identifying who stand benefit from...
The prevalence of fibromuscular dysplasia (FMD) in patients with cervical artery dissection (CAD) is unknown. Our objectives were to assess the risk CAD recurring as a stroke or transient ischemic attack and association these events FMD.We prospectively included followed 103 consecutive who had been admitted for CAD. median follow-up was 4 years (range months 10 years). main criteria inclusion mural hematoma demonstrated by magnetic resonance imaging and/or signs suggesting on 2 other...
Abstract Increasingly, repeat expansions are being identified as part of the complex genetic architecture amyotrophic lateral sclerosis. To date, several have been genetically associated with disease: intronic in C9orf72, polyglutamine ATXN2 and polyalanine NIPA1. Together previously published data, identification an sclerosis patient a family history spinocerebellar ataxia type 1, caused by ATXN1, suggested similar disease association for expansion ATXN1. We, therefore, performed...
The COVID-19 pandemic presents two main concerns for patients with myasthenia gravis (MG); chronic immunosuppression may put them at greater risk, and some proposed treatments could cause MG exacerbation.
Neurodegenerative diseases are challenging for systems biology because of the lack reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease. CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling neuronal survival, overexpression of ameliorates ALS phenotypes in vivo. Genome-wide association studies localize a large proportion risk variants within the non-coding genome, but further characterization has been limited by lack appropriate tools. By designing applying pipeline to identify pathogenic genetic variation enhancer...