Pharmacotherapy for Traumatic Brain Injury: The Next Generation of Clinical Trials
(Source: Neurotherapeutics)
Source: Neurotherapeutics - September 12, 2023 Category: Neurology Source Type: research
Phosphodiesterase-5 (PDE-5) Inhibitors as Therapy for Cerebrovascular Dysfunction in Chronic Traumatic Brain Injury
AbstractMultiple phase III randomized controlled trials (RCTs) for pharmacologic interventions in traumatic brain injury (TBI) have failed despite promising results in experimental models. The heterogeneity of TBI, in terms of pathomechanisms and impacted brain structures, likely contributes to these failures. Biomarkers have been recommended to identify patients with relevant pathology (predictive biomarkers) and confirm target engagement and monitor therapy response (pharmacodynamic biomarkers). Our group focuses on traumatic cerebrovascular injury as an understudied endophenotype of TBI and is validating a predictive an...
Source: Neurotherapeutics - September 11, 2023 Category: Neurology Source Type: research
Functional Brain Networks to Evaluate Treatment Responses in Parkinson ’s Disease
AbstractNetwork analysis of functional brain scans acquired with [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, to map cerebral glucose metabolism), or resting-state functional magnetic resonance imaging (rs-fMRI, to map blood oxygen level-dependent brain activity) has increasingly been used to identify and validate reproducible circuit abnormalities associated with neurodegenerative disorders such as Parkinson ’s disease (PD). In addition to serving as imaging markers of the underlying disease process, these networks can be used singly or in combination as an adjunct to clinical diagnosis and as a scree...
Source: Neurotherapeutics - September 8, 2023 Category: Neurology Source Type: research
Evolving Therapeutic Options for the Treatment of Duchenne Muscular Dystrophy
AbstractDuchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy. It is caused by mutations in theDMD gene, leading to reduced or absent expression of the dystrophin protein. Clinically, this results in loss of ambulation, cardiomyopathy, respiratory failure, and eventually death. In the past decades, the use of corticosteroids has slowed down the disease progression. More recently, the development of genetically mediated therapies has emerged as the most promising treatment for DMD. These strategies include exon skipping with antisense oligonucleotides, gene replacement therapy with adeno-...
Source: Neurotherapeutics - September 6, 2023 Category: Neurology Source Type: research
Neurosteroid Receptor Modulators for Treating Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) triggers wide-ranging pathology that impacts multiple biochemical and physiological systems, both inside and outside the brain. Functional recovery in patients is impeded by early onset brain edema, acute and chronic inflammation, delayed cell death, and neurovascular disruption. Drug treatments that target these deficits are under active development, but it seems likely that fully effective therapy may require interruption of the multiplicity of TBI-induced pathological processes either by a cocktail of drug treatments or a single pleiotropic drug. The complex and highly interconnected...
Source: Neurotherapeutics - August 31, 2023 Category: Neurology Source Type: research
Application of P7C3 Compounds to Investigating and Treating Acute and Chronic Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) is a leading worldwide cause of disability, and there are currently no medicines that prevent, reduce, or reverse acute or chronic neurodegeneration in TBI patients. Here, we review the target-agnostic discovery of nicotinamide adenine dinucleotide (NAD+)/NADH-stabilizing P7C3 compounds through a phenotypic screen in mice and describe how P7C3 compounds have been applied to advance understanding of the pathophysiology and potential treatment of TBI. We summarize how P7C3 compounds have been shown across multiple laboratories to mitigate disease progression safely and effectively in a br...
Source: Neurotherapeutics - August 31, 2023 Category: Neurology Source Type: research
Neurosteroid Receptor Modulators for Treating Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) triggers wide-ranging pathology that impacts multiple biochemical and physiological systems, both inside and outside the brain. Functional recovery in patients is impeded by early onset brain edema, acute and chronic inflammation, delayed cell death, and neurovascular disruption. Drug treatments that target these deficits are under active development, but it seems likely that fully effective therapy may require interruption of the multiplicity of TBI-induced pathological processes either by a cocktail of drug treatments or a single pleiotropic drug. The complex and highly interconnected...
Source: Neurotherapeutics - August 31, 2023 Category: Neurology Source Type: research
Application of P7C3 Compounds to Investigating and Treating Acute and Chronic Traumatic Brain Injury
AbstractTraumatic brain injury (TBI) is a leading worldwide cause of disability, and there are currently no medicines that prevent, reduce, or reverse acute or chronic neurodegeneration in TBI patients. Here, we review the target-agnostic discovery of nicotinamide adenine dinucleotide (NAD+)/NADH-stabilizing P7C3 compounds through a phenotypic screen in mice and describe how P7C3 compounds have been applied to advance understanding of the pathophysiology and potential treatment of TBI. We summarize how P7C3 compounds have been shown across multiple laboratories to mitigate disease progression safely and effectively in a br...
Source: Neurotherapeutics - August 31, 2023 Category: Neurology Source Type: research
An Understated Comorbidity: The Impact of Homelessness on Traumatic Brain Injury
AbstractTraumatic brain injury (TBI), a neurovascular injury caused by external force, is a common diagnosis among veterans and those experiencing homelessness (HL). There is a significant overlap in the veteran and homeless population, possibly accounting for the two to seven times greater incidence of TBI among those experiencing HL than the general population. Despite these statistics, individuals experiencing HL are often underdiagnosed and ineffectively treated for TBI. We introduced a novel model of HL. Over 5 weeks, adult Sprague–Dawley rats were randomly assigned to one of the following conditions: TBI only, HL...
Source: Neurotherapeutics - August 28, 2023 Category: Neurology Source Type: research
Interleukin-1 Receptor Antagonist as Therapy for Traumatic Brain Injury
AbstractTraumatic brain injury is a common type of acquired brain injury of varying severity carrying potentially deleterious consequences for the afflicted individuals, families, and society. Following the initial, traumatically induced insult, cellular injury processes ensue. These are believed to be amenable to treatment. Among such injuries, neuroinflammation has gained interest and has become a specific focus for both experimental and clinical researchers. Neuroinflammation is elicited almost immediately following trauma, and extend for a long time, possibly for years, after the primary injury. In the acute phase, the...
Source: Neurotherapeutics - August 23, 2023 Category: Neurology Source Type: research
Effectiveness of Ocrelizumab in Primary Progressive Multiple Sclerosis: a Multicenter, Retrospective, Real-world Study (OPPORTUNITY)
AbstractOcrelizumab is a recombinant humanized monoclonal antibody selectively targeting CD20-expressing B cells. The effect of ocrelizumab on primary progressive multiple sclerosis (PPMS) has been evaluated during phase 3 trials that enrolled patients under 55 years with a maximum Expanded Disability Status Scale (EDSS) of 6.5. However, little is known on older disabled patients with longer disease duration. We aimed to assess the clinical effectiveness of ocrelizumab in PPMS patients out of the ORATORIO eligibility criteria. This multicenter retrospect ive study collected data about the effectiveness of ocrelizumab in ...
Source: Neurotherapeutics - August 23, 2023 Category: Neurology Source Type: research
