D-galactose Supplementation for the Treatment of Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE): A Pilot Trial of Precision Medicine After Epilepsy Surgery
AbstractMOGHE is defined as mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Approximately half of the patients with histopathologically confirmed MOGHE carry a brain somatic variant in theSLC35A2 gene encoding a UDP-galactose transporter. Previous research showed that D-galactose supplementation results in clinical improvement in patients with a congenital disorder of glycosylation due to germline variants inSLC35A2. We aimed to evaluate the effects of D-galactose supplementation in patients with histopathologically confirmed MOGHE, with uncontrolled seizures or cognitive impairment...
Source: Neurotherapeutics - June 6, 2023 Category: Neurology Source Type: research
Evolving Thrombolytics: from Alteplase to Tenecteplase
AbstractAlteplase has been the primary thrombolytic used in the treatment of acute ischemic stroke since thrombolysis was first established as an effective treatment of acute ischemic stroke in 1995. Tenecteplase, a genetically modified tissue plasminogen activator, has gained attention as an attractive alternative to alteplase given its practical workflow advantages and possible superior efficacy in large vessel recanalization. As more data is analyzed both from randomized trials and non-randomized patient registries, there is mounting support that tenecteplase appears to be at least equally, if not more, safe and potenti...
Source: Neurotherapeutics - June 5, 2023 Category: Neurology Source Type: research
Axonal Transport Defect in Gigaxonin Deficiency Rescued by Tubastatin A
SummaryGiant axonal neuropathy (GAN) is a disease caused by a deficiency of gigaxonin, a mediator of the degradation of intermediate filament (IF) proteins. A lack of gigaxonin alters the turnover of IF proteins, provoking accumulation and disorganization of neurofilaments (NFs) in neurons, a hallmark of the disease. However, the effects of IF disorganization on neuronal function remain unknown. Here, we report that cultured embryonic dorsal root ganglia (DRG) neurons derived fromGan−/− mice exhibit accumulations of IF proteins and defects in fast axonal transport of organelles. Kymographs generated by time-lapse mic...
Source: Neurotherapeutics - June 2, 2023 Category: Neurology Source Type: research
Machine Learning in Clinical Trials: A Primer with Applications to Neurology
AbstractWe reviewed foundational concepts in artificial intelligence (AI) and machine learning (ML) and discussed ways in which these methodologies may be employed to enhance progress in clinical trials and research, with particular attention to applications in the design, conduct, and interpretation of clinical trials for neurologic diseases. We discussed ways in which ML may help to accelerate the pace of subject recruitment, provide realistic simulation of medical interventions, and enhance remote trial administration via novel digital biomarkers and therapeutics. Lastly, we provide a brief overview of the technic...
Source: Neurotherapeutics - May 30, 2023 Category: Neurology Source Type: research
Peripheral Administration of the Kv1.3-Blocking Peptide HsTX1[R14A] Improves Cognitive Performance in Senescence Accelerated SAMP8 Mice
In this study, we show that microglial expression of Kv1.3 is increased in senescence accelerated mice (SAMP8), an animal model of sporadic AD, and that subcutaneous dosing of HsTX1[R14A] (1 mg/kg) every other day for 8 weeks provided a robust improvement in cognitive deficits in SAMP8 mice. The effect of HsTX1[R14A] on the whole brain was assessed using tr anscriptomics, which revealed that the expression of genes associated with inflammation, neuron differentiation, synapse function, learning and memory were altered by HsTX1[R14A] treatment. Further study is required to investigate whether these changes are downstream ...
Source: Neurotherapeutics - May 24, 2023 Category: Neurology Source Type: research
Racial and Ethnic Disparities in Stroke Reperfusion Therapy in the USA
AbstractRacial and ethnic inequities in stroke care are ubiquitous. Acute reperfusion therapies, i.e., IV thrombolysis (IVT) and mechanical thrombectomy (MT), are central to acute stroke care and are highly efficacious at preventing death and disability after stroke. Disparities in the use of IVT and MT in the USA are pervasive and contribute to worse outcomes among racial and ethnic minority individuals with ischemic stroke. A meticulous understanding of disparities and underlying root causes is necessary in order to develop targeted mitigation strategies with lasting effects. This review details racial and ethnic dispari...
Source: Neurotherapeutics - May 23, 2023 Category: Neurology Source Type: research
Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes
AbstractWe aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots ...
Source: Neurotherapeutics - May 22, 2023 Category: Neurology Source Type: research
Resveratrol Preconditioning Protects Against Ischemia-Induced Synaptic Dysfunction and Cofilin Hyperactivation in the Mouse Hippocampal Slice
AbstractPerturbations in synaptic function are major determinants of several neurological diseases and have been associated with cognitive impairments after cerebral ischemia (CI). Although the mechanisms underlying CI-induced synaptic dysfunction have not been well defined, evidence suggests that early hyperactivation of the actin-binding protein, cofilin, plays a role. Given that synaptic impairments manifest shortly after CI, prophylactic strategies may offer a better approach to prevent/mitigate synaptic damage following an ischemic event. Our laboratory has previously demonstrated that resveratrol preconditioning (RPC...
Source: Neurotherapeutics - May 19, 2023 Category: Neurology Source Type: research
