Nightmare Disorder and Isolated Sleep Paralysis
AbstractNightmare disorder and recurrent isolated sleep paralysis are rapid eye movement (REM) parasomnias that cause significant distress to those who suffer from them. Nightmare disorder can cause insomnia due to fear of falling asleep through dread of nightmare occurrence. Hyperarousal and impaired fear extinction are involved in nightmare generation, as well as brain areas involved in emotion regulation. Nightmare disorder is particularly frequent in psychiatric disorders and posttraumatic stress disorder. Nonmedication treatment, in particular imagery rehearsal therapy, is especially effective. Isolated sleep paralysi...
Source: Neurotherapeutics - November 23, 2020 Category: Neurology Source Type: research

Cannabidiol Modulates Behavioural and Gene Expression Alterations Induced by Spontaneous Cocaine Withdrawal
AbstractThe aim of this study was to evaluate the effects of cannabidiol (CBD) on the behavioural and gene expression changes in a new animal model of spontaneous cocaine withdrawal. For this purpose, male CD-1 mice were exposed to progressive increasing doses of cocaine for 12  days (15 to 60 mg/kg/day, i.p.), evaluating spontaneous cocaine withdrawal 6 h after the last cocaine administration. The effects of CBD (10, 20, and 40 mg/kg, i.p.) were evaluated on cocaine withdrawal–induced alterations in motor activity, somatic signs, and anxiety-like behaviour. Furtherm ore, gene expression changes i...
Source: Neurotherapeutics - November 23, 2020 Category: Neurology Source Type: research

Positive Airway Pressure Therapy in Sleep-Disordered Breathing
AbstractObstructive sleep apnea (OSA) is a highly prevalent condition with major neurocognitive and cardiovascular health effects. Positive airway pressure (PAP) therapy prevents the collapse of the pharyngeal airway to improve hypoxemia, hypercapnia, and sleep fragmentation caused by OSA. While adherence to PAP therapy has been thought to be a barrier to use, consistent usage is likely much higher than commonly thought. In addition, many strategies have been developed to assist providers in improving their patients ’ PAP adherence. (Source: Neurotherapeutics)
Source: Neurotherapeutics - November 23, 2020 Category: Neurology Source Type: research

Overlapping Molecular Pathways Leading to Autism Spectrum Disorders, Fragile X Syndrome, and Targeted Treatments
AbstractAutism spectrum disorders (ASD) are subdivided into idiopathic (unknown) etiology and secondary, based on known etiology. There are hundreds of causes of ASD and most of them are genetic in origin or related to the interplay of genetic etiology and environmental toxicology. Approximately 30 to 50% of the etiologies can be identified when using a combination of available genetic testing. Many of these gene mutations are either core components of the Wnt signaling pathway or their modulators. The full mutation of the fragile X mental retardation 1 (FMR1) gene leads to fragile X syndrome (FXS), the most common cause o...
Source: Neurotherapeutics - November 19, 2020 Category: Neurology Source Type: research

BDNF rs6265 Variant Alters Outcomes with Levodopa in Early-Stage Parkinson ’s Disease
This study investigated if theBDNF rs6265 single nucleotide polymorphism (SNP) is associated with differential outcomes with specific pharmacotherapy treatment strategies in the “NIH Exploratory Trials in PD Long-term Study 1” (NET-PD LS-1,n = 540). DNA samples were genotyped for the rs6265 SNP and others (rs11030094, rs10501087, rs1491850, rs908867, and rs1157659). The primary measures were the Unified Parkinson’s Disease Rating Scale (UPDRS) and its motor component (UPDRS-III). Groups were divided by genotype and treatment regi men (levodopa monotherapyvs levodopa with other medicationsvs ...
Source: Neurotherapeutics - November 19, 2020 Category: Neurology Source Type: research

Approaches to Disease Modification for Parkinson ’s Disease: Clinical Trials and Lessons Learned
AbstractDespite many clinical trials over the last three decades, the goal of demonstrating that a treatment slows the progression of Parkinson ’s disease (PD) remains elusive. Research advances have shed new insight into cellular pathways contributing to PD pathogenesis and offer increasingly compelling therapeutic targets. Here we review recent and ongoing clinical trials employing novel strategies toward disease modification, including those targeting alpha-synuclein and those repurposing drugs approved for other indications. Active and passive immunotherapy approaches are being studied with the goal to modify the...
Source: Neurotherapeutics - November 17, 2020 Category: Neurology Source Type: research

Approach to Cognitive Impairment in Parkinson ’s Disease
AbstractCognitive dysfunction is common in Parkinson ’s disease (PD) and predicts poor clinical outcomes. It is associated primarily with pathologic involvement of basal forebrain cholinergic and prefrontal dopaminergic systems. Impairments in executive functions, attention, and visuospatial abilities are its hallmark features with eventual involvem ent of memory and other domains. Subtle symptoms in the premotor and early phases of PD progress to mild cognitive impairment (MCI) which may be present at the time of diagnosis. Eventually, a large majority of PD patients develop dementia with advancing age and longer di...
Source: Neurotherapeutics - November 17, 2020 Category: Neurology Source Type: research

Double-Binding Botulinum Molecule with Reduced Muscle Paralysis: Evaluation in In Vitro and In Vivo Models of Migraine
AbstractWith a prevalence of 15%, migraine is the most common neurological disorder and among the most disabling diseases, taking into account years lived with disability. Current oral medications for migraine show variable effects and are frequently associated with intolerable side effects, leading to the dissatisfaction of both patients and doctors. Injectable therapeutics, which include calcitonin gene –related peptide–targeting monoclonal antibodies and botulinum neurotoxin A (BoNT/A), provide a new paradigm for treatment of chronic migraine but are effective only in approximately 50% of subjects. Here, we ...
Source: Neurotherapeutics - November 17, 2020 Category: Neurology Source Type: research

Chronic Toxoplasma gondii Infection Alleviates Experimental Autoimmune Encephalomyelitis by the Immune Regulation Inducing Reduction in IL-17A/Th17 Via Upregulation of SOCS3
This study suggests that the alleviation of EAE afterT. gondii infection is regulated in a SOCS3/STAT3/IL-17A/blood –brain barrier integrity-dependent manner. Although parasite infection would not be permitted for MS treatment, this study usingT. gondii infection identified potential targets that contribute to disease attenuation. (Source: Neurotherapeutics)
Source: Neurotherapeutics - November 17, 2020 Category: Neurology Source Type: research

Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis
AbstractMultiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it is thought to be involved in the disease pathogenesis. The present study investigated the role of post-transcriptional regulation of gene expression on the neuroinflammation related to experimental autoimmune encephalom...
Source: Neurotherapeutics - November 16, 2020 Category: Neurology Source Type: research

Correction to: Huntington Study Group Abstracts 2020
This erratum is to correct Huntington Study Group Abstracts. (Source: Neurotherapeutics)
Source: Neurotherapeutics - November 16, 2020 Category: Neurology Source Type: research

Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin
AbstractWhile anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT2A) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143  mg/kg) in 2 test sessions spaced 2 weeks apart. Subjects maintained headache diaries starting 2 weeks before the first session until 2 weeks after the second session. Physiological and psychological drug effects were monito...
Source: Neurotherapeutics - November 12, 2020 Category: Neurology Source Type: research

The Treatment of Sleep Dysfunction in Neurodegenerative Disorders
AbstractSleep dysfunction is highly prevalent across the spectrum of neurodegenerative conditions and is a key determinant of quality of life for both patients and their families. Mounting recent evidence also suggests that such dysfunction exacerbates cognitive and affective clinical features of neurodegeneration, as well as disease progression through acceleration of pathogenic processes. Effective assessment and treatment of sleep dysfunction in neurodegeneration is therefore of paramount importance; yet robust therapeutic guidelines are lacking, owing in part to a historical paucity of effective treatments and trials. ...
Source: Neurotherapeutics - November 11, 2020 Category: Neurology Source Type: research

Overcoming Barriers to Parkinson Disease Trial Participation: Increasing Diversity and Novel Designs for Recruitment and Retention
AbstractParkinson disease (PD) is highly prevalent among neurodegenerative diseases, affecting a diverse patient population. Despite a general willingness of patients to participate in clinical trials, only a subset of patients enroll in them. Understanding the barriers to trial participation will help to alleviate this discrepancy and improve trial participation. Underrepresented minorities, older patients, and patients with more medical comorbidities in particular are underrepresented in research. In clinical trials, this has the effect of delaying trial completion, exacerbating disparities, and limiting our ability to g...
Source: Neurotherapeutics - November 4, 2020 Category: Neurology Source Type: research

Sleep-Related Breathing Disorders: When CPAP Is Not Enough
AbstractThree decades ago, continuous positive airway pressure (CPAP) was introduced to treat obstructive sleep apnea (OSA). Shortly after, bilevel positive airway pressure devices (BPAP) that independently adjusted inspiratory and expiratory positive airway pressure were developed to treat complex sleep-related breathing disorders unresponsive to CPAP. Based on the bilevel positive airway pressure platform (hardware) governed by propriety algorithms (software), advanced modes of noninvasive ventilation (NIV) were developed to address complex cardiorespiratory pathophysiology beyond OSA. This review summarizes key aspects ...
Source: Neurotherapeutics - November 4, 2020 Category: Neurology Source Type: research

Ethyl Pyruvate –Derived Transdifferentiation of Astrocytes to Oligodendrogenesis in Cuprizone-Induced Demyelinating Model
AbstractAstrocytes redifferentiate into oligodendrogenesis, raising the possibility that astrocytes may be a potential target in the treatment of adult demyelinated lesion. Upon the basis of the improvement of behavior abnormality and demyelination by ethyl pyruvate (EP) treatment, we further explored whether EP affects the function of astrocytes, especially the transdifferentiation of astrocytes into oligodendrogenesis. The results showed that EP treatment increased the accumulation of astrocytes in myelin sheath and promoted the phagocytosis of myelin debris by astrocytesin vivo andin vitro. At the same time, EP treatmen...
Source: Neurotherapeutics - November 2, 2020 Category: Neurology Source Type: research

Gene and Cell-Based Therapies for Parkinson ’s Disease: Where Are We?
AbstractParkinson ’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainst ay for treatment of motor complications of advanced disease, but these have very significant drawbacks and offer no element of disease modification. In fact, there are currently no agents that are established to modify the course of the disease in clinical use for PD. Gene and cell therapies for PD are now...
Source: Neurotherapeutics - October 30, 2020 Category: Neurology Source Type: research

Blockers of Wnt3a, Wnt10a, or β-Catenin Prevent Chemotherapy-Induced Neuropathic Pain In Vivo
In conclusion, chemotherapy increases Wnt3a, Wnt10a, and β-catenin in DRG and their pharmacological blockers prevent and amelio rate CINP, suggesting a target for the prevention and treatment of CINP. (Source: Neurotherapeutics)
Source: Neurotherapeutics - October 30, 2020 Category: Neurology Source Type: research

A Nitroalkene Benzoic Acid Derivative Targets Reactive Microglia and Prolongs Survival in an Inherited Model of ALS via NF- κB Inhibition
AbstractMotor neuron degeneration and neuroinflammation are the most striking pathological features of amyotrophic lateral sclerosis (ALS). ALS currently has no cure and approved drugs have only a modest clinically therapeutic effect in patients. Drugs targeting different deleterious inflammatory pathways in ALS appear as promising therapeutic alternatives. Here, we have assessed the potential therapeutic effect of an electrophilic nitroalkene benzoic acid derivative, (E)-4-(2-nitrovinyl) benzoic acid (BANA), to slow down paralysis progression when administered after overt disease onset in SOD1G93A rats. BANA exerted a sig...
Source: Neurotherapeutics - October 28, 2020 Category: Neurology Source Type: research

Surgical Treatment of Parkinson ’s Disease: Devices and Lesion Approaches
AbstractSurgical treatments have transformed the management of Parkinson ’s disease (PD). Therapeutic options available for the management of PD motor complications include deep brain stimulation (DBS), ablative or lesioning procedures (pallidotomy, thalamotomy, subthalamotomy), and dopaminergic medication infusion devices. The decision to pursue these advanced treatme nt options is typically done by a multidisciplinary team by considering factors such as the patient’s clinical characteristics, efficacy, ease of use, and risks of therapy with a goal to improve PD symptoms and quality of life. DBS has become the...
Source: Neurotherapeutics - October 28, 2020 Category: Neurology Source Type: research

Iron and Ferroptosis as Therapeutic Targets in Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD), one of the most common neurodegenerative diseases worldwide, has a devastating personal, familial, and societal impact. In spite of profound investment and effort, numerous clinical trials targeting amyloid-β, which is thought to have a causative role in the disease, have not yie lded any clinically meaningful success to date. Iron is an essential cofactor in many physiological processes in the brain. An extensive body of work links iron dyshomeostasis with multiple aspects of the pathophysiology of AD. In particular, regional iron load appears to be a risk factor for more r ap...
Source: Neurotherapeutics - October 27, 2020 Category: Neurology Source Type: research

α6GABA A Receptor Positive Modulators Alleviate Migraine-like Grimaces in Mice via Compensating GABAergic Deficits in Trigeminal Ganglia
AbstractMigraine is caused by hyperactivity of the trigeminovascular system, where trigeminal ganglia (TG) play an important role. This hyperactivity might originate from an underfunctional GABAergic system in TG. To investigate this possibility, we adapted a mouse model of migraine by inducing migraine-like grimaces in male mice via repeated injections of nitroglycerin (NTG, 10  mg/kg, i.p.), once every 2 days, for up to 5 sessions. Migraine-like facial pain scores were measured using the mouse grimace scale. Repeated NTG treatments in mice caused significant increases in migraine-like grimaces that were aborted...
Source: Neurotherapeutics - October 27, 2020 Category: Neurology Source Type: research

Treatment of Dystonia: Medications, Neurotoxins, Neuromodulation, and Rehabilitation
This article reviews existing evidence for treatments from each of these categories. To date, there are many examples of incomplete response to available treatments, and improved therapies are needed. (Source: Neurotherapeutics)
Source: Neurotherapeutics - October 23, 2020 Category: Neurology Source Type: research

Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System
AbstractGo-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine. In clinical practice, GJG is effective against neuropathic pain and hypersensitivity induced by chemotherapy or diabetes. In our previous study using a chronic constriction injury mouse model, we showed that GJG inhibited microglia activation by suppressing the expression of tumor necrosis factor- α (TNF-α) and p38 mitogen-activated protein kinase (p38 MAPK) in the peripheral nervous system. To investigate whether GJG can suppress inflammation in the central nervous system (CNS) in the context of neurological disorders, we examined the ef...
Source: Neurotherapeutics - October 20, 2020 Category: Neurology Source Type: research

Huntington Study Group Abstracts 2020
(Source: Neurotherapeutics)
Source: Neurotherapeutics - October 20, 2020 Category: Neurology Source Type: research

Withaferin-A Treatment Alleviates TAR DNA-Binding Protein-43 Pathology and Improves Cognitive Function in a Mouse Model of FTLD
AbstractWithaferin-A, an active withanolide derived from the medicinal herbal plantWithania somnifera induces autophagy, reduces TDP-43 proteinopathy, and improves cognitive function in transgenic mice expressing mutant TDP-43 modelling FTLD. TDP-43 is a nuclear DNA/RNA-binding protein with cellular functions in RNA transcription and splicing. Abnormal cytoplasmic aggregates of TDP-43 occur in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). To date, no effective treatment is available...
Source: Neurotherapeutics - October 19, 2020 Category: Neurology Source Type: research

Amnion-Derived Multipotent Progenitor Cells Suppress Experimental Optic Neuritis and Myelitis
AbstractThe human amnion has been used for decades in wound healing, particularly burns. Amnion epithelial cells (AECs) have been the focus of extensive research based on their possible pluripotent differentiation ability. A novel, cultured cell population derived from AECs, termed human amnion –derived multipotent progenitor (AMP) cells, secrete numerous cytokines and growth factors that enhance tissue regeneration and reduce inflammation. This AMP cell secretome, termed ST266, is a unique biological solution that accumulates in eyes and optic nerves following intranasal delivery, resul ting in selective suppression...
Source: Neurotherapeutics - October 16, 2020 Category: Neurology Source Type: research

Novel Analgesics with Peripheral Targets
AbstractA limited number of peripheral targets generate pain. Inflammatory mediators can sensitize these. The review addresses targets acting exclusively or predominantly on sensory neurons, mediators involved in inflammation targeting sensory neurons, and mediators involved in a more general inflammatory process, of which an analgesic effect secondary to an anti-inflammatory effect can be expected. Different approaches to address these systems are discussed, including scavenging proinflammatory mediators, applying anti-inflammatory mediators, and inhibiting proinflammatory or facilitating anti-inflammatory receptors. New ...
Source: Neurotherapeutics - October 15, 2020 Category: Neurology Source Type: research

Aligning New Approaches to Accelerate the Development of Non-opioid Analgesic Therapies
(Source: Neurotherapeutics)
Source: Neurotherapeutics - October 14, 2020 Category: Neurology Source Type: research

The Pharmacogenetics of Rituximab: Potential Implications for Anti-CD20 Therapies in Multiple Sclerosis
AbstractThere are a broad range of disease-modifying therapies (DMTs) available in relapsing-remitting multiple sclerosis (RRMS), but limited biomarkers exist to personalise DMT choice. All DMTs, including monoclonal antibodies such as rituximab and ocrelizumab, are effective in preventing relapses and preserving neurological function in MS. However, each agent harbours its own risk of therapeutic failure or adverse events. Pharmacogenetics, the study of the effects of genetic variation on therapeutic response or adverse events, could improve the precision of DMT selection. Pharmacogenetic studies of rituximab in MS patien...
Source: Neurotherapeutics - October 14, 2020 Category: Neurology Source Type: research

Lentiviral Interleukin-10 Gene Therapy Preserves Fine Motor Circuitry and Function After a Cervical Spinal Cord Injury in Male and Female Mice
We examined behavioral recovery using a ladder beam, tissue sparing using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2  weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12 weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons, axon s, and muscle innervation at 2 weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ...
Source: Neurotherapeutics - October 13, 2020 Category: Neurology Source Type: research

CREB Participates in Paclitaxel-Induced Neuropathic Pain Genesis Through Transcriptional Activation of Dnmt3a in Primary Sensory Neurons
AbstractChemotherapy-induced peripheral neuropathic pain (CIPNP) often occurs in cancer patients treated with antineoplastic drugs. Therapeutic management of CIPNP is very limited, at least in part due to the largely unknown mechanisms that underlie CIPNP genesis. Here, we showed that systemic administration of the chemotherapeutic drug paclitaxel significantly and time-dependently increased the levels of cyclic AMP response element-binding protein (CREB) in dorsal root ganglion (DRG) neurons. Blocking this increase through DRG microinjection ofCreb siRNA attenuated paclitaxel-induced mechanical, heat, and cold nociceptive...
Source: Neurotherapeutics - October 13, 2020 Category: Neurology Source Type: research

Levistolide A Attenuates Alzheimer ’s Pathology Through Activation of the PPARγ Pathway
AbstractAlzheimer ’s disease (AD) is a neurodegenerative disease characterized by β-amyloid (Aβ) protein deposition, neurofibrillary tangle (NFT) formation, and neuronal loss in the brain. The current study was designed to investigate the potential mechanisms by which levistolide A affects the pathogenesis of AD in an amyloid precursor protein/presenilin 1 (APP/PS1) transgenic (Tg) mouse model of AD and N2a/APP695swe cells. Specifically, behavioral changes in levistolide A–treated APP/PS1 Tg mice were assessed by the nest-building and Morris water maze (MWM) tests. Levistolide A treatment clearly amel...
Source: Neurotherapeutics - October 9, 2020 Category: Neurology Source Type: research

Modulation of the Microbiome in Parkinson ’s Disease: Diet, Drug, Stool Transplant, and Beyond
AbstractThe gastrointestinal microbiome is altered in Parkinson ’s disease and likely plays a key role in its pathophysiology, affecting symptoms and response to therapy and perhaps modifying progression or even disease initiation. Gut dysbiosis therefore has a significant potential as a therapeutic target in Parkinson’s disease, a condition elusive to disea se-modifying therapy thus far. The gastrointestinal environment hosts a complex ecology, and efforts to modulate the relative abundance or function of established microorganisms are still in their infancy. Still, these techniques are being rapidly developed...
Source: Neurotherapeutics - October 9, 2020 Category: Neurology Source Type: research

Central Nervous System Targets: Inhibitory Interneurons in the Spinal Cord
AbstractPain is a percept of critical importance to our daily survival. In most cases, it serves both an adaptive function by helping us respond appropriately in a potentially hostile environment and also a protective role by alerting us to tissue damage. Normally, it is evoked by the activation of peripheral nociceptive nerve endings and the subsequent relay of information to distinct cortical and sub-cortical regions, but under pathological conditions that result in chronic pain, it can become spontaneous. Given that one in three chronic pain patients do not respond to the treatments currently available, the need for mor...
Source: Neurotherapeutics - October 6, 2020 Category: Neurology Source Type: research

Sleep Issues in Parkinson ’s Disease and Their Management
AbstractParkinson ’s disease (PD) is an alpha-synucleinopathy that leads to prominent motor symptoms including tremor, bradykinesia, and postural instability. Nonmotor symptoms including autonomic, neurocognitive, psychiatric symptoms, and sleep disturbances are also seen frequently in PD. The impact of PD on sleep is related to motor and nonmotor symptoms, in addition to the disruption of the pathways regulating sleep by central nervous system pathology. Rapid eye movement sleep behavior disorder is a parasomnia that can lead to self-injury and/or injury to partners at night. Restless legs syndrome is a subj ective ...
Source: Neurotherapeutics - October 6, 2020 Category: Neurology Source Type: research

Behavioral, Hormonal, Inflammatory, and Metabolic Effects Associated with FGF21-Pathway Activation in an ALS Mouse Model
In this study, we aimed to determine the relevance of FGF21 pathway stimulation in a male mouse model of ALS (mutatedSOD1-G93A mice) by using a pharmacological agonist of FGF21, R1Mab1. Mice (SOD1-WT and mutant SOD1-G93A) were treated with R1Mab1 or vehicle. Longitudinal data about clinical status (motor function, body weight) and biological parameters (including hormonal, immunological, and metabolomics profiles) were collected from the first symptoms to euthanasia at week 20. Multivariate models were performed to identify the main parameters associated with R1Mab1 treatment and to link them with clinical status, and meta...
Source: Neurotherapeutics - October 5, 2020 Category: Neurology Source Type: research

Update on the Treatment of Ataxia: Medication and Emerging Therapies
AbstractWhile rehabilitation therapies always help patients with ataxia, there are currently no FDA-approved treatments for ataxia. Medications are available to treat symptoms that may complicate an ataxic illness, e.g., tremor, myoclonus, dystonia, and rigidity, which are discussed elsewhere in this volume. Spasticity, pain, fatigue, depression, sleep disturbances, cognitive decline, and bowel and bladder dysfunction, if they occur, all have multiple available drugs and therapies for symptomatic use. There is also an extensive literature on off-label uses of various medications to improve imbalance. The pipeline of emergi...
Source: Neurotherapeutics - October 5, 2020 Category: Neurology Source Type: research

P2X3-Containing Receptors as Targets for the Treatment of Chronic Pain
AbstractCurrent therapies for the treatment of chronic pain provide inadequate relief for millions of suffering patients, demonstrating the need for better therapies that will treat pain effectively and improve the quality of patient ’s lives. Better understanding of the mechanisms that mediate chronic pain is critical for developing drugs with improved clinical outcomes. Adenosine triphosphate (ATP) is a key modulator in nociceptive pathways. Release of ATP from injured tissue or sympathetic efferents has sensitizing effects on sensory neurons in the periphery, and presynaptic vesicular release of ATP from the centr...
Source: Neurotherapeutics - October 1, 2020 Category: Neurology Source Type: research

A Highly Selective MNK Inhibitor Rescues Deficits Associated with Fragile X Syndrome in Mice
AbstractFragile X syndrome (FXS) is the most common inherited source of intellectual disability in humans. FXS is caused by mutations that trigger epigenetic silencing of theFmr1 gene. Loss ofFmr1 results in increased activity of the mitogen-activated protein kinase (MAPK) pathway. An important downstream consequence is activation of the mitogen-activated protein kinase interacting protein kinase (MNK). MNK phosphorylates the mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E). Excessive phosphorylation of eIF4E has been directly implicated in the cognitive and behavioral deficits associated with FXS. Pharmac...
Source: Neurotherapeutics - September 30, 2020 Category: Neurology Source Type: research

Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3
We report that the treatment of epSPCs and human pluripotent stem cell –derived neural progenitors (hPSC-NPs) with the GSK-3 inhibitor Ro3303544 activates β-catenin signaling and increases the expression of the bIII-tubulin neuronal marker; furthermore, the differentiation of Ro3303544-treated cells prompted an increase in the number of terminally differentiated neu rons. Administration of a water-soluble, bioavailable form of this GSK-3 inhibitor (Ro3303544-Cl) in a severe SCI mouse model revealed the increased expression of bIII-tubulin in the injury epicenter. Treatment with Ro3303544-Cl increased survival of...
Source: Neurotherapeutics - September 29, 2020 Category: Neurology Source Type: research

Relapses in Patients Treated with High-Dose Biotin for Progressive Multiple Sclerosis
AbstractHigh-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), b...
Source: Neurotherapeutics - September 21, 2020 Category: Neurology Source Type: research

Methionine-Mediated Protein Phosphatase 2A Catalytic Subunit (PP2Ac) Methylation Ameliorates the Tauopathy Induced by Manganese in Cell and Animal Models
In conclusion, our data suggest that SAM and PP2Ac methylation may be novel targets for the treatment of Mn poisoning and neurotoxic mechanism-related tauopathies. (Source: Neurotherapeutics)
Source: Neurotherapeutics - September 20, 2020 Category: Neurology Source Type: research

Prolonged Beneficial Effect of Brief Erythropoietin Peptide JM4 Therapy on Chronic Relapsing EAE
AbstractPotent beneficial immunomodulatory and anti-inflammatory effects of whole-molecule erythropoietin have been demonstrated in a variety of animal disease models including experimental autoimmune encephalomyelitis (EAE); however, excessive hematopoiesis limits its use in clinical applications. Our group previously generated an Epo-derived small peptide JM4 that is side-effect free and has strong neuroprotective activity without hematologic effects. Here, we investigated the long-term clinical effects of brief treatment with JM4 in chronic relapsing EAE using bioluminescence imaging (BLI) in transgenic mice containing ...
Source: Neurotherapeutics - September 20, 2020 Category: Neurology Source Type: research

FTH1 Inhibits Ferroptosis Through Ferritinophagy in the 6-OHDA Model of Parkinson ’s Disease
AbstractParkinson ’s disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons associated with dysregulation of iron homeostasis in the brain. Ferroptosis is an iron-dependent cell death process that serves as a significant regulatory mechanism in PD. However, its underlying mechanisms are not yet fully understood. By performing RNA sequencing analysis, we found that the main iron storage protein ferritin heavy chain 1 (FTH1) is differentially expressed in the rat 6-hydroyxdopamine (6-OHDA) model of PD compared with control rats. Our present work demonstrates that FTH1 is invo...
Source: Neurotherapeutics - September 20, 2020 Category: Neurology Source Type: research

Pharmacological Treatment of Early Motor Manifestations of Parkinson Disease (PD)
AbstractParkinson disease (PD), as a slowly progressive neurodegenerative disorder, undergoes six neuropathological stages. The earliest clinical manifestation presents in the middle stage of the disorder pathologically, when 50% or more of the dopaminergic neurons have degenerated in the substantia nigra. This discrepancy between the early stage clinically and that pathologically has, in part, spurred the debate as to when it is best to initiate symptomatic therapy. The most well-studied monotherapeutic agents for PD in its early course include levodopa (the cornerstone of PD therapy), dopamine agonists, and monoamine oxi...
Source: Neurotherapeutics - September 14, 2020 Category: Neurology Source Type: research

Neuronal Adenylyl Cyclase Targeting Central Plasticity for the Treatment of Chronic Pain
AbstractChronic pain is a major health problem and the effective treatment for chronic pain is still lacking. The recent crisis created by the overuse of opioids for pain treatment has clearly shown the need for non-addictive novel pain medicine. Conventional pain medicines usually inhibit peripheral nociceptive transmission and reduce central transmission, especially pain-related excitatory transmission. For example, both opioids and gabapentin produce analgesic effects by inhibiting the release of excitatory transmitters and reducing neuronal excitability. Here, we will review recent studies of central synaptic plasticit...
Source: Neurotherapeutics - September 14, 2020 Category: Neurology Source Type: research

Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood –Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats
AbstractBrain edema is a vital contributor to early brain injury after subarachnoid hemorrhage (SAH), which is responsible for prolonged hospitalization and poor outcomes. Pharmacological therapeutic targets on edema formation have been the focus of research for decades. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to participate in neural development and brain injury. Here, we used PACAP knockout CRISPR to demonstrate that endogenous PACAP plays an endogenous neuroprotective role against brain edema formation after SAH in rats. The exogenous PACAP treatment provided both short- and long-term n...
Source: Neurotherapeutics - September 10, 2020 Category: Neurology Source Type: research

Managing Essential Tremor
We present our treatment algorithm. (Source: Neurotherapeutics)
Source: Neurotherapeutics - September 10, 2020 Category: Neurology Source Type: research

Emerging Targeted Therapeutics for Genetic Subtypes of Parkinsonism
AbstractIn recent years, a precision medicine approach, which customizes medical treatments based on patients ’ individual profiles and incorporates variability in genes, the environment, and lifestyle, has transformed medical care in numerous medical fields, most notably oncology. Applying a similar approach to Parkinson’s disease (PD) may promote the development of disease-modifying agents that could help slow progression or possibly even avert disease development in a subset of at-risk individuals. The urgent need for such trials partially stems from the negative results of clinical trials where intervention...
Source: Neurotherapeutics - September 9, 2020 Category: Neurology Source Type: research