Repurposing Pomalidomide as a Neuroprotective Drug: Efficacy in an Alpha-Synuclein-Based Model of Parkinson ’s Disease
AbstractMarketed drugs for Parkinson ’s disease (PD) treat disease motor symptoms but are ineffective in stopping or slowing disease progression. In the quest of novel pharmacological approaches that may target disease progression, drug-repurposing provides a strategy to accelerate the preclinical and clinical testing of drugs alread y approved for other medical indications. Here, we targeted the inflammatory component of PD pathology, by testing for the first time the disease-modifying properties of the immunomodulatory imide drug (IMiD) pomalidomide in a translational rat model of PD neuropathology based on the int...
Source: Neurotherapeutics - January 24, 2022 Category: Neurology Source Type: research

Correction to: Peripheral Neuropathy: No Longer the  Land of Therapeutic Nihilism
(Source: Neurotherapeutics)
Source: Neurotherapeutics - January 24, 2022 Category: Neurology Source Type: research

Antibody Therapies in Autoimmune Encephalitis
AbstractAutoimmune encephalitis (AE) comprises a heterogeneous group of disorders in which the host immune system targets self-antigens expressed in the central nervous system. The most conspicuous example is an anti-N-methyl-d-aspartate receptor encephalitis linked to a complex neuropsychiatric syndrome. Current treatment of AE is based on immunotherapy and has been established according to clinical experience and along the concept of a B cell-mediated pathology induced by highly specific antibodies to neuronal surface antigens. In general, immunotherapy for AE follows an escalating approach. When first-line therapy with ...
Source: Neurotherapeutics - January 20, 2022 Category: Neurology Source Type: research

Phenotype Shifting in Astrocytes Account for Benefits of Intra-Arterial Selective Cooling Infusion in Hypertensive Rats of Ischemic Stroke
AbstractThe translational failure of neuroprotective therapies in stroke may be influenced by the mismatch of existing comorbidities between animal models and patients. Previous studies found that single-target neuroprotective agents reduced infarction in Sprague –Dawley but not in spontaneously hypertensive rats. It is of great interest to explore whether multi-target neuroprotectants and stroke models with comorbidities should be used in further translational researches. Ischemic stroke was induced in normotensive or hypertensive rats by 90- or 120-min m iddle cerebral artery occlusion (MCAO) and reperfusion. Intra...
Source: Neurotherapeutics - January 19, 2022 Category: Neurology Source Type: research

Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors
AbstractThe introduction of immune checkpoint inhibitors (ICIs) in oncologic therapies has led to a paradigm shift in cancer treatment. ICIs have increased the overall survival in patients with malignant melanoma, small-cell lung cancer, and many other tumor entities. Despite their clinical benefits, these novel cancer immunotherapies can induce neurological immune-related adverse events (irAEs). Such immune-mediated complications can manifest within the spectrum of paraneoplastic neurological syndromes (PNSs). PNSs are rare immune-mediated complications of systemic cancers that can involve every aspect of the nervous syst...
Source: Neurotherapeutics - January 18, 2022 Category: Neurology Source Type: research

An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
AbstractWhile behavioral interventions remain the mainstay of treatment of autism spectrum disorder (ASD), several potential targeted treatments addressing the underlying neurophysiology of ASD have emerged in the last few years. These are promising for the potential to, in future, become part of the mainstay treatment in addressing the core symptoms of ASD. Although it is likely that the development of future targeted treatments will be influenced by the underlying heterogeneity in etiology, associated genetic mechanisms influencing ASD are likely to be the first targets of treatments and even gene therapy in the future f...
Source: Neurotherapeutics - January 14, 2022 Category: Neurology Source Type: research

Emotional and Neuropsychiatric Disorders Associated with Alzheimer ’s Disease
AbstractAlzheimer ’s disease is associated with impairments in emotional communication including comprehension and production of facial emotional expressions, comprehension of affective prosody, and alexithymia. It is also associated with disorders of emotional experience including mood disorders (depression and an xiety), agitation/aggression, and psychosis. Agitation/aggression and psychosis are particularly disruptive, are associated with earlier institutionalization, and pose a major challenge to institutional management. Treatment of disorders of emotional experience has been primarily pharmacologic (revi ewed h...
Source: Neurotherapeutics - January 10, 2022 Category: Neurology Source Type: research

L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants
AbstractPathogenic missense variants inGRIN2A andGRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals withGRIN2A- orGRIN2B-related disorders who were treated with L-serine, each within an independentn-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a ...
Source: Neurotherapeutics - January 7, 2022 Category: Neurology Source Type: research

Neonatal Fc Receptor –Targeted Therapies in Neurology
AbstractAutoantibodies are increasingly recognized for their pathogenic potential in a growing number of neurological diseases. While myasthenia gravis represents the prototypic antibody (Ab)-mediated neurological disease, many more disorders characterized by Abs targeting neuronal or glial antigens have been identified over the past two decades. Depletion of humoral immune components including immunoglobulin G (IgG) through plasma exchange or immunoadsorption is a successful therapeutic strategy in most of these disease conditions. The neonatal Fc receptor (FcRn), primarily expressed by endothelial and myeloid cells, faci...
Source: Neurotherapeutics - January 7, 2022 Category: Neurology Source Type: research

L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants
AbstractPathogenic missense variants inGRIN2A andGRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals withGRIN2A- orGRIN2B-related disorders who were treated with L-serine, each within an independentn-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a ...
Source: Neurotherapeutics - January 7, 2022 Category: Neurology Source Type: research

Neonatal Fc Receptor –Targeted Therapies in Neurology
AbstractAutoantibodies are increasingly recognized for their pathogenic potential in a growing number of neurological diseases. While myasthenia gravis represents the prototypic antibody (Ab)-mediated neurological disease, many more disorders characterized by Abs targeting neuronal or glial antigens have been identified over the past two decades. Depletion of humoral immune components including immunoglobulin G (IgG) through plasma exchange or immunoadsorption is a successful therapeutic strategy in most of these disease conditions. The neonatal Fc receptor (FcRn), primarily expressed by endothelial and myeloid cells, faci...
Source: Neurotherapeutics - January 7, 2022 Category: Neurology Source Type: research

Peripheral Neuropathy: No Longer the Land of Therapeutic Nihilism
(Source: Neurotherapeutics)
Source: Neurotherapeutics - January 6, 2022 Category: Neurology Source Type: research

Dendrimer-2PMPA Delays Muscle Function Loss and Denervation in a Murine Model of Amyotrophic Lateral Sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease where muscle weakness and neuromuscular junction (NMJ) denervation precede motor neuron cell death. Although acetylcholine is the canonical neurotransmitter at the mammalian NMJ synapse, glutamate has recently been identified as a critical neurotransmitter for NMJ development and maintenance. One source of glutamate is through the catabolism ofN-acetyl-aspartyl-glutamate (NAAG), which is found in mM concentrations in mammalian motoneurons, where it is released upon stimulation and hydrolyzed to glutamate by the glial enzyme glutamate car...
Source: Neurotherapeutics - January 4, 2022 Category: Neurology Source Type: research

Vascular Cognitive Impairment (VCI)
AbstractVascular cognitive impairment (VCI) is predominately caused by vascular risk factors and cerebrovascular disease. VCI includes a broad spectrum of cognitive disorders, from mild cognitive impairment to vascular dementia caused by ischemic or hemorrhagic stroke, and vascular factors alone or in a combination with neurodegeneration including Alzheimer ’s disease (AD) and AD-related dementia. VCI accounts for at least 20–40% of all dementia diagnosis. Growing evidence indicates that cerebrovascular pathology is the most important contributor to dementia, with additive or synergistic interactions with neuro...
Source: Neurotherapeutics - December 22, 2021 Category: Neurology Source Type: research

Rapid Induction of Dopaminergic Neuron Loss Accompanied by Lewy Body-Like Inclusions in A53T BAC-SNCA Transgenic Mice
AbstractParkinson ’s disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) and intraneuronal α-synuclein (α-syn) inclusions. It is highly needed to establish a rodent model that recapitulates the clinicopatholog ical features of PD within a short period to efficiently investigate the pathological mechanisms and test disease-modifying therapies. To this end, we analyzed three mouse lines, i.e., wild-type mice, wild-type human α-syn bacterial artificial chromosome (BAC) transgenic (BAC-SNCA Tg) mice,...
Source: Neurotherapeutics - December 21, 2021 Category: Neurology Source Type: research

Neurobiological Opportunities in Diabetic Polyneuropathy
AbstractThis review highlights a selection of potential translational directions for the treatment of diabetic polyneuropathy (DPN) currently irreversible and without approved interventions beyond pain management. The list does not include all diabetic targets that have been generated over several decades of research but focuses on newer work. The emphasis is firstly on approaches that support the viability and growth of peripheral neurons and their ability to withstand a barrage of diabetic alterations. We include a section describing Schwann cell targets and finally how mitochondrial damage has been a common element in d...
Source: Neurotherapeutics - December 21, 2021 Category: Neurology Source Type: research

Genomics and Functional Genomics of Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is a complex and multifactorial neurodegenerative disease. Due to its long clinical course and lack of an effective treatment, AD has become a major public health problem in the USA and worldwide. Due to variation in age-at-onset, AD is classified into early-onset (
Source: Neurotherapeutics - December 21, 2021 Category: Neurology Source Type: research

Rapid Induction of Dopaminergic Neuron Loss Accompanied by Lewy Body-Like Inclusions in A53T BAC-SNCA Transgenic Mice
AbstractParkinson ’s disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) and intraneuronal α-synuclein (α-syn) inclusions. It is highly needed to establish a rodent model that recapitulates the clinicopatholog ical features of PD within a short period to efficiently investigate the pathological mechanisms and test disease-modifying therapies. To this end, we analyzed three mouse lines, i.e., wild-type mice, wild-type human α-syn bacterial artificial chromosome (BAC) transgenic (BAC-SNCA Tg) mice,...
Source: Neurotherapeutics - December 21, 2021 Category: Neurology Source Type: research

Neurobiological Opportunities in Diabetic Polyneuropathy
AbstractThis review highlights a selection of potential translational directions for the treatment of diabetic polyneuropathy (DPN) currently irreversible and without approved interventions beyond pain management. The list does not include all diabetic targets that have been generated over several decades of research but focuses on newer work. The emphasis is firstly on approaches that support the viability and growth of peripheral neurons and their ability to withstand a barrage of diabetic alterations. We include a section describing Schwann cell targets and finally how mitochondrial damage has been a common element in d...
Source: Neurotherapeutics - December 21, 2021 Category: Neurology Source Type: research

Genomics and Functional Genomics of Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is a complex and multifactorial neurodegenerative disease. Due to its long clinical course and lack of an effective treatment, AD has become a major public health problem in the USA and worldwide. Due to variation in age-at-onset, AD is classified into early-onset (
Source: Neurotherapeutics - December 21, 2021 Category: Neurology Source Type: research

EEG Neurofeedback in the Treatment of Adults with Binge-Eating Disorder: a Randomized Controlled Pilot Study
AbstractSpecific alterations in electroencephalography (EEG)-based brain activity have recently been linked to binge-eating disorder (BED), generating interest in treatment options targeting these neuronal processes. This randomized-controlled pilot study examined the effectiveness and feasibility of two EEG neurofeedback paradigms in the reduction of binge eating, eating disorder and general psychopathology, executive functioning, and EEG activity. Adults with BED and overweight (N = 39) were randomly assigned to either a food-specific EEG neurofeedback paradigm, aiming at reducing fronto-central beta activi...
Source: Neurotherapeutics - December 20, 2021 Category: Neurology Source Type: research

Correction to: Deferiprone Treatment in Aged Transgenic Tau Mice Improves Y-Maze Performance and Alters Tau Pathology
(Source: Neurotherapeutics)
Source: Neurotherapeutics - December 14, 2021 Category: Neurology Source Type: research

Correction to: ASENT2020 Annual Meeting Abstracts
(Source: Neurotherapeutics)
Source: Neurotherapeutics - December 14, 2021 Category: Neurology Source Type: research

Correction to: Deferiprone Treatment in Aged Transgenic Tau Mice Improves Y-Maze Performance and Alters Tau Pathology
(Source: Neurotherapeutics)
Source: Neurotherapeutics - December 14, 2021 Category: Neurology Source Type: research

Correction to: ASENT2020 Annual Meeting Abstracts
(Source: Neurotherapeutics)
Source: Neurotherapeutics - December 14, 2021 Category: Neurology Source Type: research

The Cannabidiol Analog PECS-101 Prevents Chemotherapy-Induced Neuropathic Pain via PPAR γ Receptors
AbstractChemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting adverse effect of chemotherapy drugs such as paclitaxel (PTX). PTX causes marked molecular and cellular damage, mainly in the peripheral nervous system, including sensory neurons in the dorsal root ganglia (DRG). Several studies have shown the therapeutic potential of cannabinoids, including cannabidiol (CBD), the major non-psychotomimetic compound found in the Cannabis plant, to treat peripheral neuropathies. Here, we investigated the efficacy of PECS-101 (former HUF-101), a CBD fluorinated analog, on PTX-induced neuropathic pain in mice. ...
Source: Neurotherapeutics - December 13, 2021 Category: Neurology Source Type: research

Chronic Administration of 13-cis-retinoic Acid Induces Depression-Like Behavior by Altering the Activity of Dentate Granule Cells
AbstractDepression is a common but serious mental disorder and can be caused by the side effects of medications. Evidence from abundant clinical case reports and experimental animal models has revealed the association between the classic anti-acne drug 13-cis-retinoic acid (13-cis-RA) and depressive symptoms. However, direct experimental evidence of this mechanism and information on appropriate therapeutic rescue strategies are lacking. Herein, our data revealed that chronic administration of 13-cis-RA to adolescent mice induced depression-like behavior but not anxiety-like behavior. We next demonstrated that chronic 13-ci...
Source: Neurotherapeutics - December 10, 2021 Category: Neurology Source Type: research

Chemogenetic Seizure Control with Clozapine and the Novel Ligand JHU37160 Outperforms the Effects of Levetiracetam in the Intrahippocampal Kainic Acid Mouse Model
AbstractExpression of inhibitory designer receptors exclusively activated by designer drugs (DREADDs) on excitatory hippocampal neurons in the hippocampus represents a potential new therapeutic strategy for drug-resistant epilepsy. To overcome the limitations of the commonly used DREADD agonist clozapine, we investigated the efficacy of the novel DREADD ligand JHU37160 in chemogenetic seizure suppression in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). In addition, seizure-suppressing effects of chemogenetics were compared to the commonly used anti-epileptic drug (AED), levetiracetam...
Source: Neurotherapeutics - December 3, 2021 Category: Neurology Source Type: research

Immunogenicity and safety of mRNA COVID-19 vaccines in people with multiple sclerosis treated with different disease-modifying therapies
AbstractThe potential impact of disease-modifying therapies (DMTs) for multiple sclerosis (MS) on COVID-19 vaccination is poorly understood. According to recent observations, the humoral immune response could be impaired in patients treated with ocrelizumab or fingolimod. Our study evaluated the immunogenicity and safety of mRNA COVID-19 vaccines in a convenience sample of 140 MS patients treated with different DMTs, undergoing vaccination between April and June 2021. Humoral immune response was tested 1  month after the second dose, using a chemiluminescent microparticle immunoassay to detect IgG against SARS-CoV-2 n...
Source: Neurotherapeutics - December 3, 2021 Category: Neurology Source Type: research

Chemogenetic Seizure Control with Clozapine and the Novel Ligand JHU37160 Outperforms the Effects of Levetiracetam in the Intrahippocampal Kainic Acid Mouse Model
AbstractExpression of inhibitory designer receptors exclusively activated by designer drugs (DREADDs) on excitatory hippocampal neurons in the hippocampus represents a potential new therapeutic strategy for drug-resistant epilepsy. To overcome the limitations of the commonly used DREADD agonist clozapine, we investigated the efficacy of the novel DREADD ligand JHU37160 in chemogenetic seizure suppression in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). In addition, seizure-suppressing effects of chemogenetics were compared to the commonly used anti-epileptic drug (AED), levetiracetam...
Source: Neurotherapeutics - December 3, 2021 Category: Neurology Source Type: research

Immunogenicity and safety of mRNA COVID-19 vaccines in people with multiple sclerosis treated with different disease-modifying therapies
AbstractThe potential impact of disease-modifying therapies (DMTs) for multiple sclerosis (MS) on COVID-19 vaccination is poorly understood. According to recent observations, the humoral immune response could be impaired in patients treated with ocrelizumab or fingolimod. Our study evaluated the immunogenicity and safety of mRNA COVID-19 vaccines in a convenience sample of 140 MS patients treated with different DMTs, undergoing vaccination between April and June 2021. Humoral immune response was tested 1  month after the second dose, using a chemiluminescent microparticle immunoassay to detect IgG against SARS-CoV-2 n...
Source: Neurotherapeutics - December 3, 2021 Category: Neurology Source Type: research

Intranasal Delivery of a Methyllanthionine-Stabilized Galanin Receptor-2-Selective Agonist Reduces Acute Food Intake
AbstractThe regulatory (neuro)peptide galanin is widely distributed in the central and peripheral nervous systems, where it mediates its effects via three G protein-coupled receptors (GAL1-3R). Galanin has a vast diversity of biological functions, including modulation of feeding behavior. However, the clinical application of natural galanin is not practicable due to its rapid in vivo breakdown by peptidases and lack of receptor subtype specificity. Much effort has been put into the development of receptor-selective agonists and antagonists, and while receptor selectivity has been attained to some degree, most ligands show ...
Source: Neurotherapeutics - December 2, 2021 Category: Neurology Source Type: research

Magnetic Resonance Neurography: Improved Diagnosis of Peripheral Neuropathies
AbstractPeripheral neuropathies account for the most frequent disorders seen by neurologists, and causes are manifold. The traditional diagnostic gold-standard consists of clinical neurologic examinations supplemented by nerve conduction studies. Due to well-known limitations of standard diagnostics and atypical clinical presentations, establishing the correct diagnosis can be challenging but is critical for appropriate therapies. Magnetic resonance neurography (MRN) is a relatively novel technique that was developed for the high-resolution imaging of the peripheral nervous system. In focal neuropathies, whether traumatic ...
Source: Neurotherapeutics - December 2, 2021 Category: Neurology Source Type: research

Lewy Body Dementias: Controversies and Drug Development
AbstractLewy body dementia (LBD) is one of the most common neurodegenerative dementias. Clinical trials for symptomatic and disease-modifying therapies in LBD remain a national research priority, but there are many challenges in both past and active drug developments in LBD. This review highlights the controversies in picking the appropriate populations, interventions, target selections, and outcome measures, which are all critical components of clinical trial implementation in LBD. The heterogeneity of LBD neuropathology and clinical presentations, limited understanding of core features such as cognitive fluctuations, and...
Source: Neurotherapeutics - December 2, 2021 Category: Neurology Source Type: research

Correction to: Fluid Biomarkers for Monitoring Structural Changes in Polyneuropathies: Their Use in Clinical Practice and Trials
(Source: Neurotherapeutics)
Source: Neurotherapeutics - December 2, 2021 Category: Neurology Source Type: research

Intranasal Delivery of a Methyllanthionine-Stabilized Galanin Receptor-2-Selective Agonist Reduces Acute Food Intake
AbstractThe regulatory (neuro)peptide galanin is widely distributed in the central and peripheral nervous systems, where it mediates its effects via three G protein-coupled receptors (GAL1-3R). Galanin has a vast diversity of biological functions, including modulation of feeding behavior. However, the clinical application of natural galanin is not practicable due to its rapid in vivo breakdown by peptidases and lack of receptor subtype specificity. Much effort has been put into the development of receptor-selective agonists and antagonists, and while receptor selectivity has been attained to some degree, most ligands show ...
Source: Neurotherapeutics - December 2, 2021 Category: Neurology Source Type: research

Magnetic Resonance Neurography: Improved Diagnosis of Peripheral Neuropathies
AbstractPeripheral neuropathies account for the most frequent disorders seen by neurologists, and causes are manifold. The traditional diagnostic gold-standard consists of clinical neurologic examinations supplemented by nerve conduction studies. Due to well-known limitations of standard diagnostics and atypical clinical presentations, establishing the correct diagnosis can be challenging but is critical for appropriate therapies. Magnetic resonance neurography (MRN) is a relatively novel technique that was developed for the high-resolution imaging of the peripheral nervous system. In focal neuropathies, whether traumatic ...
Source: Neurotherapeutics - December 2, 2021 Category: Neurology Source Type: research

Lewy Body Dementias: Controversies and Drug Development
AbstractLewy body dementia (LBD) is one of the most common neurodegenerative dementias. Clinical trials for symptomatic and disease-modifying therapies in LBD remain a national research priority, but there are many challenges in both past and active drug developments in LBD. This review highlights the controversies in picking the appropriate populations, interventions, target selections, and outcome measures, which are all critical components of clinical trial implementation in LBD. The heterogeneity of LBD neuropathology and clinical presentations, limited understanding of core features such as cognitive fluctuations, and...
Source: Neurotherapeutics - December 2, 2021 Category: Neurology Source Type: research

Correction to: Fluid Biomarkers for Monitoring Structural Changes in Polyneuropathies: Their Use in Clinical Practice and Trials
(Source: Neurotherapeutics)
Source: Neurotherapeutics - December 2, 2021 Category: Neurology Source Type: research