The goal of this clinical trial is to compare corresponding inter- and intraindividual pharmacokinetic and pharmacodynamic profiles including assessments of safety & tolerability.

开始日期2023-05-05

申办/合作机构

Reconnect Labs

100 项与 Dimethyltryptamine/Telepathine 相关的临床结果

登录后查看更多信息

100 项与 Dimethyltryptamine/Telepathine 相关的转化医学

登录后查看更多信息

100 项与 Dimethyltryptamine/Telepathine 相关的专利（医药）

登录后查看更多信息

项与 Dimethyltryptamine/Telepathine 相关的文献（医药）

2024-06-01·Regenerative Therapy

Novel cell therapy with ex vivo cultured peripheral blood mononuclear cells significantly impacts angiogenesis in the murine ischemic limb model

Article

作者: Tanaka, Rica ; Furukawa, Satomi ; Fujimura, Satoshi ; Hirano, Rie ; Sugawara, Ai

IntroductionAutologous mononuclear cells (MNCs) have been used in vascular regenerative therapy since the identification of endothelial progenitor cells (EPCs). However, the efficacy of autologous EPC therapy for diseases such as diabetes and connective tissue disorders is limited due to deficiencies in the number and function of EPCs. To address this, we developed a novel RE-01 cells that enriches pro-angiogenic cells from peripheral blood MNCs (PBMNCs).MethodsPBMNCs were collected from healthy volunteers following ethical guidelines. RE-01 cells were cultured in the presence of specific growth factors for 5 days without media change. Flow cytometry was used to analyze cell surface markers. Tube formation assays, EPC culture assays, and mRNA analysis were performed to evaluate angiogenic potential. The efficacy of RE-01 cells upon transplantation into ischemic hind limbs of mice was evaluated.ResultsRE-01 cells exhibited a significant increase in pro-angiogenic cells such as M2 macrophages and angiogenic T cells, in contrast to PBMNCs, while the number of inflammatory cells reduced. In vitro assays demonstrated the enhanced angiogenic abilities of RE-01 cells, supported by increased mRNA expression of angiogenesis-related cytokines. In vivo studies using mouse ischemic hind limb models have shown that blood flow and angiogenesis improved following RE-01 cell transplantation. Transplantations for 3 consecutive days significantly improved the number of pericyte-recruited vessels in the severely ischemic hind limbs of mice.ConclusionsRE-01 cells showed promising results in enhancing angiogenesis and arteriogenesis, possibly owing to the presence of M2 macrophages and angiogenic T cells. These cells also demonstrated anti-fibrotic effects. The efficacy of RE-01 cells has been confirmed in mouse models, suggesting their potential for treating ischemic vascular diseases. Clinical trials are planned to validate the safety and efficacy of RE-01 cell therapy in patients with connective tissue disease and unhealed ulcers. We hope that this new RE-01 cell therapy will prevent many patients from undergoing amputation.

2020-09-01·The Journal of Physiology2区 · 医学

Modulation of Kv3.1/Kv3.2 promotes gamma oscillations by rescuing Aβ‐induced desynchronization of fast‐spiking interneuron firing in an AD mouse model in vitro

2区 · 医学

Article

作者: Arroyo‐García, Luis Enrique ; Andrade‐Talavera, Yuniesky ; Chen, Gefei ; Johansson, Jan ; Fisahn, André

Key points

Gamma oscillations (30–80 Hz) are important for cognitive functions and depend on the synchronized activity of fast‐spiking interneurons (FSN), which is crucial for network stability.

Gamma oscillations are degraded in Alzheimer's disease (AD) patients exhibiting cognitive impairment, with the degree of cognitive decline correlating with the severity of gamma disruption in response to neurotoxic amyloid‐beta peptide (Aβ).

Small molecule compounds EX15 and RE01 modulate Kv3.1/Kv3.2 potassium channels on FSN, resulting in faster activation kinetics and increased firing frequency, suggesting direct consequences for cognition‐relevant gamma oscillations, particularly in a situation where network activity is pathologically compromised in the presence of neurotoxic Aβ.

Using electrophysiological techniques in an in vitro AD model, we found a significant effect of EX15 and RE01 with respect to counteracting toxic Aβ effects on neuronal dynamics, advocating for targeting FSN activity to rescue cognitive performance from impairment caused by neurodegenerative triggers.

AbstractRhythmic electrical activity in neuronal networks such as gamma oscillations (30–80 Hz) underlies cognitive functions such as sensory perception, attention and memory. Gamma oscillations are disrupted in Alzheimer's disease (AD) patients and animal AD models, with the severity of cognitive decline correlating with the degree of rhythm disruption. Misfolded amyloid‐β peptide (Aβ) is assumed to be a key trigger of AD pathology and has been show to de‐synchronize action potential firing in fast‐spiking interneurons (FSN), which is crucial for entraining neuronal network activity into the gamma rhythm. The synchronizing activity of FSN therefore has become one of the most suitable targets to counteract disease‐driven degradation of gamma oscillations and consequent cognitive decline. EX15 and RE01 are small‐molecule compounds that modulate Kv3.1/Kv3.2 potassium channels, resulting in faster activation kinetics and increased FSN firing frequency. In the present study, we investigated the potential pro‐cognitive effects of EX15 and RE01 by testing their ability to modulate FSN activity during ongoing gamma oscillations in normal and Aβ‐disrupted network states in mouse hippocampus in vitro. In the compromised, but not the uncompromised, network state with gamma oscillations partially disrupted by Aβ, both compounds improve gamma oscillation regularity by promoting re‐synchronization of FSN action potential firing. Our data suggest a therapeutic potential for compounds such as EX15 and RE01, which can rescue normal action potential firing parameters in FSN, in the search for disease‐modifying drug candidates counteracting the progressive dysfunction of neuronal network dynamics that underlies the cognitive impairment typical of AD and other cognitive brain disorders.

2018-08-01·European Journal of Pharmacology3区 · 医学

Pharmacological rescue of mutated Kv3.1 ion-channel linked to progressive myoclonus epilepsies

3区 · 医学

Article

作者: Anders Sonne Munch ; Thomas Jespersen ; Morten Grunnet ; Charlotte Hougaard ; Kim Boddum ; Arnela Saljic

Progressive myoclonus epilepsies (PMEs) constitute a cluster of inherent, genetically diverse, rare seizure disorders characterized by ataxia, tonic-clonic seizures, and action myoclonus. Recently, a mutation in the KCNC1 gene (Arg320His) was described in a group of PME patients. The KCNC1 gene encodes the K_v3.1 potassium ion channel responsible for the rapid repolarization of the membrane potential following action potential firing in fast spiking GABAergic interneurons (FSI), thereby enabling high firing frequency. In the present study, we demonstrate that the Arg320His mutation cause a reduction in the K_v3.1 current amplitude and acts in a dominantly negative fashion. The mutation profoundly affects channel activation and deactivation kinetics, and we further find that it impairs recruitment of the K_v3.1 channel to the plasma membrane. The K_v3 activating compound, RE01, partly rescues the electrophysiological deficit, suggesting that pharmacological activation of K_v3.1 activity might be a feasible approach for treatment of this cohort of PME patients.

100 项与 Dimethyltryptamine/Telepathine 相关的药物交易

登录后查看更多信息