A5070193666- Tuberous Sclerosis Complex Research
- Epilepsy research and treatment
- Pharmacological Effects and Toxicity Studies
- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Renal cell carcinoma treatment
- Neuroscience and Neuropharmacology Research
- Neurogenetic and Muscular Disorders Research
- Pharmaceutical studies and practices
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Congenital Anomalies and Fetal Surgery
- Histiocytic Disorders and Treatments
- Genomics and Rare Diseases
- Vascular Tumors and Angiosarcomas
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Connective tissue disorders research
- Pain Management and Placebo Effect
- Renal and related cancers
- Glycogen Storage Diseases and Myoclonus
- Cardiac electrophysiology and arrhythmias
- Chemical Reactions and Isotopes
Ministry of Health of the Russian Federation
2016-2025
Pirogov Russian National Research Medical University
2016-2025
Velti (Greece)
2023
Schlumberger (Russia)
2018
Moscow Clinical Scientific Center
2018
Scientific Center of Children's Health
2016
Regional Clinical Research
2016
Hanover College
2016
Oncology Hematology Care
2016
V.M. Koretsky Institute of State and Law
2014
Background Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs) and other manifestations tuberous sclerosis complex (TSC). However, long-term use mTOR inhibitors might be necessary. This analysis explored safety everolimus from the conclusion EXIST-1 study (NCT00789828). Methods Findings was an international, prospective, double-blind, placebo-controlled phase 3 trial examining patients with new or...
Objectives We examined the long-term effects of everolimus in patients with renal angiomyolipoma associated tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Methods Following favorable results from double-blind core phase EXIST-2 (NCT00790400), were allowed to receive open-label (extension phase). Patients initially randomly assigned continued on same dose; those who receiving placebo crossed over 10 mg/day. Dose modifications based tolerability. The primary end point was...
Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double-blind, placebo-controlled trial presented. Following favorable results the primary analysis (data cutoff 30 June 2011) EXIST-2 trial, patients still receiving study were allowed to enter an...
BackgroundTuberous sclerosis complex (TSC) is characterized by benign tumours in multiple organs, including the brain, kidneys, skin, lungs and heart. Our objective was to evaluate everolimus, an mTOR inhibitor, treatment of angiomyolipoma patients with subependymal giant cell astrocytoma (SEGA) associated TSC.
Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology management of TSC, several questions remain unanswered. A disease registry could be effective tool to gain more insights into TSC thus help development improved strategies. TuberOus SClerosis increase Awareness (TOSCA) multicentre, international assess manifestations,...
To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens decline in ambulatory ability boys with Duchenne muscular dystrophy (DMD).Three hundred thirty-one participants DMD 7 14 years of age taking glucocorticoids were tadalafil 0.3 mg·kg-1·d-1, 0.6 or placebo. The efficacy measure was 6-minute walk distance (6MWD) after weeks. Secondary measures included North Star Ambulatory Assessment and timed function tests....
Spinal muscular atrophy 5q (SMA) is one of the most common inherited neuromuscular diseases in children with an autosomal recessive type inheritance. Homozygous deletion exons 7 or 7–8 SMN1 gene encoding motor neuron survival protein responsible for 95 % cases. SMA characterized by a steadily progressive course development paresis, muscle atrophy, loss previously acquired skills, respiratory failure and skeletal deformities. The introduction pathogenetic therapy recent years has...
A reduction in renal angiomyolipoma volume observed with everolimus (EVE) treatment patients tuberous sclerosis complex (TSC) has been postulated to translate clinical benefit by reducing the risk of hemorrhage and chronic failure.The long-term effects EVE on function (∼4 years treatment) were examined treated Phase 3 EXIST-1 EXIST-2 studies. Patients had TSC subependymal giant cell astrocytoma (SEGA), a definite diagnosis or sporadic lymphangioleiomyomatosis. was administered at 4.5...
Patients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney. This was a post hoc analysis of pediatric patients being treated for subependymal giant cell astrocytomas (SEGAs) during phase 3, randomized, double-blind, placebo-controlled EXIST-1 trial. were initially randomly assigned to receive everolimus 4.5 mg/m2/day (target blood trough 5–15 mg/dl) or placebo could continue an open-label extension phase. Angiomyolipoma...
Abstract Background Tuberous sclerosis complex ( TSC ) is a genetic disorder associated with tumour growth in various organs, including the brain, kidneys, heart and skin. Cutaneous lesions are prevalent manifestations of , occurring up to 90% patients. Oral mammalian target rapamycin inhibitors, such as everolimus, believed be effective for treatment ‐associated because they act on underlying disease pathophysiology. Objective We evaluated long‐term effect oral everolimus skin secondary...
Introduction The EXIST-2 (NCT00790400) study demonstrated the superiority of everolimus over placebo for treatment renal angiomyolipomas associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). This post hoc analysis aimed to assess angiomyolipoma tumor behavior among patients who submitted continued radiographic examination following discontinuation in noninterventional follow-up phase. Methods For discontinued at completion extension phase reasons other...
Spinal muscular atrophy (SMA) is a hereditary, autosomal recessive disease that debuts at different ages. Neurological symptoms are progressive and lead to significant limitation of life activity reduced expectancy. Currently, there several drugs for the pathogenetical treatment SMA. This article reflects evolution clinicians’ views on patients with SMA as scientific evidence from clinical trials experience in managing real‑world practice accumulates. The biggest debate about 4 copies SMN2...
The progress of genetic diagnostic methods and a significant improvement in the quality next-generation sequencing (NGS) have led to revolution study genetics epilepsy. Genome-wide (PSG) is «gold standard» research epilepsy.Material methods. was performed 168 probands aged from 1 month 18 years with suspected diagnosis PSG prescribed patients who, alongside epilepsy, had delayed intellectual/speech development and/or motor disorders behavioral disorders.Results. According results PSG,...
Epileptic encephalopathies (EE) are the group of progressive conditions with various etiologies that can produce neurocognitive deficit both per se and due to constant epileptiform discharges. constitute about 15% epilepsy in childhood 40% all seizures occurring first 3 years life. Ten syndrome forms EE identified. Genetic factors contribute 70-80% epileptic diseases approximately idiopathic epilepsies have a monogenic mode inheritance. Thirty-five genes been identified search is still...
356 Background: We evaluated everolimus, an oral mTOR inhibitor, for treating angiomyolipoma (AML) in patients with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sLAM). Methods: EXIST-2 ( NCT00790400 ) is a prospective, international, randomized, double-blind, placebo-controlled, phase III study. Patients (≥1 AML longest diameter ≥3 cm) were stratified by (i) TSC and enzyme-inducing anti-epileptic drug (EIAED) use, (ii) EIAED non-use, (iii) sLAM randomized 2:1 to...
Angelman syndrome is a genetic disorder characterized by mental retardation and severe speech delay, movement disorders ataxia, dysmorphic features, behavioral disorders. caused the loss of 15q11.2-q13 region chromosome 15 received from mother, which leads to violation expression UBE3A gene. Purpose. To analyze clinical manifestations in children with identify early-onset characteristic signs. Characteristics research methods. The study included 60 children. In all cases, was diagnosed on...
Cognitive problems in epilepsy have a multifactorial origin with etiology, seizures, and the «central» side-effects of drug treatment being involved. side effects antiepileptic drugs (AEDs) been demonstrated to be one most important tolerability chronic AED treatment, especially children epilepsy. Memory impairments, mental slowing, attentional deficits are frequently reported ones. Neuropsychological profiles AEDs considerations for selection, particularly adolescents. In evaluating studies...
The tuberous sclerosis complex genes (TSC1 and TSC2) function as classic tumor suppressor in health; a loss of these results activation the kinase m-TOR to development benign tumors. Despite their slow progression, renal subependymal giant cell astrocytomas angiomyolipomas can cause fatal outcomes. Both Phases I–II III EXIST-1 EXIST-2 trials demonstrated that inhibitor everolimus had good efficacy tolerability: volume angomyolipomas were reduced by 50% or more 35 41% patients, respectively....