Thomas Klopstock
A5026565602- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- ATP Synthase and ATPases Research
- Drug-Induced Ocular Toxicity
- Retinal Development and Disorders
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- Hereditary Neurological Disorders
- Parkinson's Disease Mechanisms and Treatments
- Glycogen Storage Diseases and Myoclonus
- Neurological disorders and treatments
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Genetic and rare skin diseases.
- Muscle Physiology and Disorders
- Lysosomal Storage Disorders Research
- Porphyrin Metabolism and Disorders
- Blood disorders and treatments
- Photosynthetic Processes and Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Retinal Diseases and Treatments
- Immunodeficiency and Autoimmune Disorders
Munich Cluster for Systems Neurology
2016-2025
Ludwig-Maximilians-Universität München
2016-2025
Friedrich Baur Stiftung
2016-2025
German Center for Neurodegenerative Diseases
2016-2025
LMU Klinikum
1999-2024
Istituto delle Scienze Neurologiche di Bologna
2013-2023
University of Bologna
2013-2023
Massachusetts General Hospital
2023
John Wiley & Sons (United States)
2023
Hudson Institute
2023
Abstract Mutations in the cytosine‐5 RNA methyltransferase NSun2 cause microcephaly and other neurological abnormalities mice human. How post‐transcriptional methylation contributes to human disease is currently unknown. By comparing gene expression data with global methylomes patient fibroblasts NSun2‐deficient mice, we find that loss of increases angiogenin‐mediated endonucleolytic cleavage transfer RNAs ( tRNA ) leading an accumulation 5′ ‐derived small fragments. Accumulation fragments...
Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments proven efficacy. Leber’s hereditary optic neuropathy is most common disorder causing irreversible blindness young adult life. Anecdotal reports support use idebenone neuropathy, but this has not been evaluated a randomized controlled trial. We conducted 24-week multi-centre double-blind, randomized, placebo-controlled trial 85 patients...
The identification of NOX4 as a major source oxidative stress in stroke and demonstration dramatic protection after mice by deletion or NOX inhibition, opens up new avenues for treatment.
Mutations in the gene coding for catalytic subunit of mitochondrial DNA (mtDNA) polymerase gamma (POLG1) have recently been described patients with diverse clinical presentations, revealing a complex relationship between genotype and phenotype their families. POLG1 was sequenced from different European diagnostic research centres to define phenotypic spectrum advance understanding recurrence risks. were identified 38 cases, majority being sporadic compound heterozygotes. Eighty-nine sequence...
Aging is a major risk factor for large number of disorders and functional impairments. Therapeutic targeting the aging process may therefore represent an innovative strategy in quest novel broadly effective treatments against age-related diseases. The recent report lifespan extension mice treated with FDA-approved mTOR inhibitor rapamycin represented first demonstration pharmacological maximal mammals. Longevity effects may, however, be due to rapamycin’s on specific life-limiting...
Leber hereditary optic neuropathy (LHON) is a genetic disorder primarily due to mutations of mitochondrial DNA (mtDNA). Environmental factors are thought precipitate the visual failure and explain marked incomplete penetrance LHON, but previous small studies have failed confirm this be case. LHON has no treatment, so identifying environmental triggers key disease prevention, whilst potentially revealing new mechanisms amenable therapeutic manipulation. To address issue, we conducted large,...
Summary Purpose: Epilepsies have a highly heterogeneous background with strong genetic contribution. The variety of unspecific and overlapping syndromic nonsyndromic phenotypes often hampers clear clinical diagnosis prevents straightforward testing. Knowing the basis patient’s epilepsy can be valuable not only for but also guiding treatment estimating recurrence risks. Methods: To overcome these diagnostic restrictions, we composed panel genes Next Generation Sequencing containing most...
Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history now fairly well understood. LHON also first for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by European Medicine Agency, under exceptional circumstances because of rarity severity disease. However, what remains unclear includes optimal target population, timing, dose, frequency...
At 96 weeks after unilateral intravitreal injection of rAAV2/2- ND4 , vision improved in both eyes 78% subjects affected with LHON.
Abstract Background Lack of functional evidence hampers variant interpretation, leaving a large proportion individuals with suspected Mendelian disorder without genetic diagnosis after whole genome or exome sequencing (WES). Research studies advocate to further sequence transcriptomes directly and systematically probe gene expression defects. However, collection additional biopsies establishment lab workflows, analytical pipelines, defined concepts in clinical interpretation aberrant are...
Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was first to be genetically defined by a point mutation in DNA (mtDNA). A molecular diagnosis achieved up 95% of cases, vast majority which are accounted for 3 mutations within complex I subunit–encoding genes mtDNA (mtLHON). Here, we resolve enigma LHON absence pathogenic mutations. We describe biallelic nuclear encoded gene, DNAJC30, 33 unsolved patients from 29 families establish an autosomal...
PurposeTo evaluate the efficacy of a single intravitreal injection rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON).DesignRESCUE is multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial.ParticipantsSubjects m.11778G>A mitochondrial DNA mutation and vision ≤6 months onset 1 or both eyes were included.MethodsEach subject’s right eye was randomly assigned (1:1) to treatment (single 9 × 1010 viral genomes 90 μl) sham injection. The...
In April 2023, the antisense oligonucleotide tofersen was approved by U.S. Food and Drug Administration (FDA) for treatment of
Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown be effective in stabilizing restoring patients treated within 1 year of onset The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy safety idebenone treatment (900 mg/day) with LHON up 5 years after symptom (N = 199) over period 24 months, compared an external history...