Publications by authors named "L A Bindoff"
Article Synopsis
- Mitochondrial diseases cause neuronal death and depletion of mitochondrial DNA (mtDNA), with astrocytes potentially playing a damaging role in neurodegeneration.
- Research using induced pluripotent stem cells (iPSCs) from patients with POLG mutations showed that the resulting astrocytes experienced significant mitochondrial dysfunction and developed a toxic phenotype.
- When these dysfunctioning astrocytes interacted with neurons, they induced neuronal death, highlighting a novel toxic contribution of astrocytes to the progression of POLG-related diseases.
Objective: To investigate the prevalence and natural history of POLG disease in the Norwegian population.
Methods: A national, population-based, retrospective study using demographic, clinical, and genetic data of patients with genetically confirmed POLG disease. The patients were diagnosed between 2002 and 2022, and were included into the Norwegian POLG Patient Registry.
We aimed to provide a detailed phenotypic description of status epilepticus (SE) in a large cohort of patients with POLG disease and identify prognostic biomarkers to improve the management of this life-threatening condition. In a multinational, retrospective study with data on patients with POLG disease from seven European countries, we identified those who had SE. The age of SE onset, accompanying clinical, laboratory, imaging and genetic findings were analysed.
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- A 3D brain organoid model is created to investigate POLG-related encephalopathy, a mitochondrial disease caused by POLG mutations, using patient-derived induced pluripotent stem cells (iPSCs).
- The generated cortical organoids display key disease features like abnormal structure, neuron loss, and depleted mitochondrial DNA, along with changes in critical neuronal development pathways and increased NOTCH and JAK-STAT signaling.
- Metformin treatment improved several issues found in the organoids, but did not resolve problems with inhibitory dopamine-glutamate neurons, making this model a useful tool for studying POLG disorders and related diseases linked to mitochondrial dysfunction.
Purpose: Pyridoxine-dependent epilepsy due to variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is imperative to prevent uncontrolled seizures. We have explored the role of EEG in the diagnosis and management of PDE.
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