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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse w.dalton dietrich Allan D.Levi James D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Clinical significance and potential translation of neural regeneration and functional recovery in monkeys after spinal cord injury

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Science China(Life Sciences) 2018年第10期61卷 1291-1292页

作者： w.dalton dietrich Leonard M.Miller School of Medicine University of MiamiMiami FL 33136 USA

The recent manuscript by Dr. Rao and colleagues （Rao et al., 2018） reports on a new combinational strategy that significantly promotes neural regeneration and improves motor and sensory function in nonhuman primates after severe spinal cord injury （SCI）. This acute reparative strategy that included the insertion of neurotrophin 3-loaded chitosan biodegradable material into a l-cm gap of the hemisectioned spinal cord had previously been tested in rodent models of SCI. In addition to showing that this reparative approach led to corticospinal tract axonal growth across the lesion area with extension into the distal spinal cord.

关键词：绳索新生神经翻译猴子临床最小公倍数感觉功能

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New treatment strategies targeting experimental traumatic brain injury

New treatment strategies targeting experimental traumatic br...

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第七届全国创伤学术会议暨2009海峡两岸创伤医学论坛

作者： w.dalton dietrich Department of Neurological Surgery The Miami Project to Cure Paralysis University of Miami Miller School of Medicine MiamiFL

Traumatic brain injury(TBI) results in significant hippocampal pathology and hippocampal dependent memory loss,both of which have been shown to be improved by hypothermia *** laboratory has been interested in examining the molecular mechanisms regulated by hypothermia after *** example,previous studies have assessed the effects of temperature modifications after brain injury on excitotoxicity, inflammatory and apoptotic cell death *** one recent study,the modulation of the cyclic AMP(cAMP) signaling pathway was evaluated following fluid percussion brain *** observed that TBI leads to prolonged depression of the cAMP/protein kinase A(PKA) pathway in vulnerable brain ***,although phosphodiesterase(PDE) inhibition with the typeⅣinhibitor Rolipram rescued cAMP/PKA signaling cascades,posttraumatic hypothermia had no effect on cyclic AMP levels in this ***,Rolipram treatment reduced overall contusion volume, preserved NeuN positive cells in the overlying cerebral cortex and CA3 hippocampus and inhibited increases in proinflammatory cytokines including IL-1βand TNFα.To determine the molecular pathways involved in the beneficial effects of hypothermia on learning and memory,we also investigated the effects of TBI and temperature modification on protein kinases involved in learning and *** observed that following TBI,various memory kinases including CAMKⅠ,CAMKⅡand CAMKⅣwere transiently elevated in the *** of MAPK and CREB were also ***, posttraumatic hypothermia enhanced MAPK and CREB activation prolonging the elevation of these important signaling *** have recently noticed in our studies evidence for mossy fiber sprouting in the hippocampus after *** brain injury is a major risk factor for the subsequent development of epilepsy,we chose to evaluate the effects of posttraumatic hypothermia on seizure threshold in these *** this end,animals unde

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Does being female provide a neuroprotective advantage following spinal cord injury?

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Neural Regeneration Research 2015年第10期10卷 1533-1536页

作者： Jeffrey P.Datto Jackie Yang w.dalton dietrich Damien D.Pearse The Miami Project to Cure Paralysis University of Miami Miller School of Medicine The Department of Neurological Surgery University of Miami Miller School of Medicine The Department of Neurology University of Miami Miller School of Medicine The Department of Cell Biology University of Miami Miller School of Medicine The Neuroscience Program University of Miami Miller School of Medicine The Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine

It has been controversial whether gender has any effect on recovery following spinal cord injury（SCI）. Past experimental and clinical research aimed at addressing this subject has led to constrasting findings on whether females hold any advantage in locomotor recovery. Additionally, for studies supporting the notion of a female gender related advantage, a definite cause has not been explained. In a recent study, using large sample sizes for comparative male and female spinal cord injury cohorts, we reported that a significant gender advantage favoring females existed in both tissue preservation and functional recovery after taking into consideration discrepancies in age and weight of the animals across sexes. Prior animal research frequently used sample sizes that were too small to determine significance with certainty and also did not account for two other factors that influence locomotor performance： age and weight. Our finding is important in light of controversy surrounding the effect of gender on outcome and the fact that SCI affects more than ten thousand new individuals annually, a population that is disproportionately male. By deepening our understanding of why a gender advantage exists, potential new therapeutics can be designed to improve recovery for the male population following the initial trauma or putatively augment the neuroprotective privilege in females for enhanced outcomes.

关键词： sex gender hormone neuroprotection estrogen progesterone apoptosis Schwann cell

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Models and detection of spontaneous recurrent seizures in laboratory rodents

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Zoological Research 2017年第4期38卷 171-179页

作者： Bin Gu Katherine A. dalton Department of Cell Biology and Physiology University of North Carolina Chapel Hill NC 27599 USA Psychology & Neuroscience Program University of North Carofina Chapel Hill NC 27599 USA

Epilepsy, characterized by spontaneous recurrent seizures （SRS）, is a serious and common neurological disorder afflicting an estimated 1% of the population worldwide. Animal experiments, especially those utilizing small laboratory rodents, remain essential to understanding the fundamental mechanisms underlying epilepsy and to prevent, diagnose, and treat this disease. while much attention has been focused on epileptogenesis in animal models of epilepsy, there is little discussion on SRS, the hallmark of epilepsy. This is in part due to the technical difficulties of rigorous SRS detection. In this review, we comprehensively summarize both genetic and acquired models of SRS and discuss the methodology used to monitor and detect SRS in mice and rats.

关键词： Spontaneous recurrent seizures Animal model Epilepsy

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Reviewing guppy color vision： integrating the molecular and physiological variation in visual tuning of a classic system for sensory drive

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Current Zoology 2018年第4期64卷 535-545页

作者： Benjamin SANDKAM Brian dalton Felix BREDEN Karen CARLETON Department of Biology University of Maryland College Park College Park MD 20742 USA Department of Biological Sciences Simon Fraser University Burnaby BC VSA 1S6 Canada

Sensory drive predicts coevolution of mate choice signals with the sensory systems detecting those sig nals. Guppies are a classic model for sensory drive as mate preferences based on coloration differ across individuals and populations. A large body of work has identified variation in color vision, yet we lack a dir ect tie between how such variation in color vision influences variation in color preference. Here we bring together studies that have investigated guppy vision over the past 40years to：（1） highlight our current understanding of where variation occurs in the guppy color vision pathway and （2） suggest future ave nues of research into sources of visual system variation that could influence guppy color preference. This will allow researchers to design careful studies that couple measures of color preference with measures of visual system variation from the same individual or population. Such studies will finally provide im portant answers as to what sets the direction and speed of mate preference evolution via sensory drive.

关键词： colour vision mate choice opsin Poecilia reticulata sensory bias visual ecology

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Cellulose-based materials in wastewater treatment of petroleum industry

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Green Energy & Environment 2020年第1期5卷 37-49页

作者： Baoliang Peng Zhaoling Yao Xiaocong wang Mitchel Crombeen dalton GSweeney Kam Chiu Tam Research Institute of Petroleum Exploration&Development(RIPED) PetroChinaBeijing100083China Key Laboratory of Nano Chemistry Key Laboratory of Oilfield ChemistryCNPCBeijing100083China Department of Chemical Engineering Waterloo Institute for NanotechnologyUniversity of WaterlooWaterlooOntarioN2L 3G1Canada Institute of Porous Flow&Fluid Mechanics Chinese Academy of SciencesLangfangHebei065007China

The most abundant natural biopolymer on earth, cellulose fiber, may offer a highly efficient, low-cost, and chemical-free option for wastewater treatment. Cellulose is widely distributed in plants and several marine animals. It is a carbohydrate polymer consisting of β-1,4-linked anhydro-D-glucose units with three hydroxyl groups per anhydroglucose unit(AGU). Cellulose-based materials have been used in food, industrial, pharmaceutical, paper, textile production, and in wastewater treatment applications due to their low cost, renewability,biodegradability, and non-toxicity. For water treatment in the oil and gas industry, cellulose-based materials can be used as adsorbents, flocculants, and oil/water separation membranes. In this review, the uses of cellulose-based materials for wastewater treatment in the oil & gas industry are summarized, and recent research progress in the following aspects are highlighted: crude oil spill cleaning, flocculation of solid suspended matter in drilling or oil recovery in the upstream oil industry, adsorption of heavy metal or chemicals, and separation of oil/water by cellulosic membrane in the downstream water treatment.

关键词： Cellulose wastewater treatment Petroleum industry

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Selective androgen receptor modulators for the treatment of late onset male hypogonadism

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Asian Journal of Andrology 2014年第2期16卷 256-261,I0009页

作者： Christopher C Coss Amanda Jones Michael L Hancock Mitchell S Steiner James T dalton GTx Inc. Memphis Tennessee USA.

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators （SARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

关键词： hypogonadism late onset hypogonadism selective androgen receptor modulators testosterone

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Note on the Formation of Supermassive Black Holes

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Journal of High Energy Physics, Gravitation and Cosmology 2020年第3期6卷 321-323页

作者： Kenneth dalton Th. Pongprasart Bang Saphan Prachuap Kiri Khan Thailand

Supermassive black holes formed during the lepton epoch of the Big Bang. what follows is a description of how this may have happened.

关键词： Supermassive Black Holes Electron-Positron Model

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The Explosion at the Center of Our Galaxy

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Journal of High Energy Physics, Gravitation and Cosmology 2020年第3期6卷 440-442页

作者： Kenneth dalton Th. Pongprasart Bang Saphan Prachuap Kiri Khan Thailand

At the center of the Milky way, our black hole may have suddenly changed from supermassive to intermediate-mass status. In doing so, it would have emitted an enormous burst of electromagnetic radiation. Here, the tota... 详细信息

关键词： Black Hole Explosion Fermi Bubbles

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