Publications by authors named "Thomas B Stoker"

We have developed an efficient approach to generate functional induced dopaminergic (DA) neurons from adult human dermal fibroblasts. When performing DA neuronal conversion of patient fibroblasts with idiopathic Parkinson's disease (PD), we could specifically detect disease-relevant pathology in these cells. We show that the patient-derived neurons maintain age-related properties of the donor and exhibit lower basal chaperone-mediated autophagy compared with healthy donors.

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  • Huntington's disease (HD) is a hereditary neurodegenerative disorder marked by neuropsychiatric symptoms, a movement disorder (mainly chorea), and cognitive decline, diagnosed by detecting increased CAG repeat lengths in the huntingtin gene.
  • While diagnosing HD is typically clear-cut, some patients present in atypical ways, complicating the identification of when an asymptomatic carrier develops the disease.
  • Managing HD effectively requires specialized multidisciplinary clinics, especially for genetic testing, as current treatments focus on alleviating symptoms like chorea and behavioral issues, though evidence supporting these treatments is often limited.
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  • Parkinson's disease (PD) is a neurodegenerative disorder characterized by movement issues like bradykinesia, tremors, and rigidity, with limited treatment options primarily focusing on dopamine levels.
  • Current treatments fail to address the progression of PD and non-motor symptoms, such as cognitive decline, which significantly affect patients' quality of life.
  • Emerging therapeutic strategies include drug repurposing, gene therapies, and advanced surgical techniques, which aim to improve symptoms and potentially slow the disease's progression, with many approaches already in clinical trials.
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  • Variants in certain genes are linked to an increased risk of Parkinson's disease (PD), with both pathogenic mutations and non-pathogenic variants being identified.
  • This study focused on PD patients in Cambridgeshire, examining the long-term effects of these genetic variants on issues like dementia, postural instability, and mortality.
  • Results revealed that both types of variants can lead to faster disease progression, with pathogenic variants leading to earlier death compared to non-carriers, regardless of dementia development.
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  • Direct neuronal reprogramming can be done through various methods, including using specific transcription factors or microRNAs, and reducing the influence of neuron-repressing elements.
  • There is significant variability in the quality and maturity of the induced neurons, influenced by the reprogramming strategy chosen.
  • The study finds that adding specific microRNAs (miR124 and miR9/9*) helps improve neuronal maturation, enhancing gene expression, protein levels, and electrophysiological characteristics.
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  • Parkinson's disease (PD) is a neurodegenerative disorder characterized by movement issues and non-motor symptoms, primarily caused by the loss of dopaminergic neurons in the brain.
  • Currently, there are no effective treatments to modify the disease, with existing therapies mainly focused on managing symptoms through dopaminergic drugs and some surgical options.
  • New research is exploring regenerative cell-based and gene therapies that show promise in early trials, aiming to restore dopamine levels and reduce harmful α-synuclein aggregates, potentially transforming PD management in the near future.
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  • Parkinson's disease is the second most common neurodegenerative disorder, characterized by movement issues from the loss of dopamine-producing neurons in the brain.
  • Current treatments mainly involve dopaminergic medications, which can have significant side effects, especially in later stages of the disease, highlighting the need for better solutions.
  • Advances in regenerative treatments like stem-cell therapy and viral gene delivery are being developed, with upcoming clinical trials aiming to ensure these treatments are effective, safe, and practical for patient use.
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  • Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopamine-producing neurons, leading to movement issues, and current treatments have significant side effects.
  • *Cell-based regenerative treatments aim to replace these neurons more effectively, with various sources for dopamine neurons including fetal tissue, but ethical and logistical challenges limit its widespread use.
  • *Induced pluripotent stem cells and embryonic stem cells are potential alternatives for producing neurons, with embryonic stem cells showing promise for standardized therapies, though ethical concerns remain.
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Internal carotid artery dissection is an important cause of ischaemic stroke in those aged under 50 years. Awareness of the clinical features is crucial as they may offer the opportunity to intervene to reduce strokes occurring or recurring.

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  • - Over the last 30 years, progress in regenerative cell-based therapies for neurodegenerative diseases, especially Parkinson's, has been notable, yet challenges remain, such as ethical issues and risks of immune rejection and tumor development.
  • - Fetal ventral mesencephalon grafts have shown success in preclinical trials, prompting clinical trials that demonstrate their effectiveness in certain cases.
  • - There's a growing interest in using stem cell-derived dopaminergic neurons for future clinical applications, with trials expected to start in the next few years.
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