Emerging Drugs for the Treatment of Amyotrophic Lateral Sclerosis: A Focus on Recent Phase 2 Trials.

Emerging Drugs for the Treatment of Amyotrophic Lateral Sclerosis: A Focus on Recent Phase 2 Trials. Expert Opin Emerg Drugs. 2020 May 27;:1-20 Authors: Barp A, Gerardi F, Lizio A, Sansone VA, Lunetta C Abstract INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease involving both upper and lower motor neurons and resulting in increasing disability and death 3-5 years after onset of symptoms. Over 40 large clinical trials for ALS have been negative, except for Riluzole that offers a modest survival benefit, and Edaravone that modestly reduces disease progression in patients with specific characteristics. Thus, the discovery of efficient disease modifying therapy is an urgent need. AREAS COVERED: Although the cause of ALS remains unclear, many studies have demonstrated that neuroinflammation, proteinopathies, glutamate-induced excitotoxicity, microglial activation, oxidative stress, and mitochondrial dysfunction may play a key role in the pathogenesis. This review highlights recent discoveries relating to these diverse mechanisms and their implications for the development of therapy. Ongoing phase 2 clinical trials aimed to interfere with these pathophysiological mechanisms are discussed. EXPERT OPINION: This review describes the challenges that the discovery of an efficient drug therapy faces and how these issues may be addressed. With the continuous advances coming from basic research, we provide...
Source: Expert Opinion on Emerging Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Emerg Drugs Source Type: research

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This study aimed to characterize the role of BDNF in age-related microglial activation. Initially, we found that degrees of microglial activation were especially evident in the substantia nigra (SN) across different brain regions of aged mice. The levels of BDNF and TrkB in microglia decreased with age and negatively correlated with their activation statuses in mice during aging. Interestingly, aging-related microglial activation could be reversed by chronic, subcutaneous perfusion of BDNF. Peripheral lipopolysaccharide (LPS) injection-induced microglial activation could be reduced by local supplement of BDNF, while shTrkB...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Multiple sclerosis (MS) is a central nervous system inflammatory demyelinating disease and the most common cause of non-traumatic disability in young adults. Despite progress in the treatment of the active relapsing disease, therapeutic options targeting irreversible progressive decline remain limited. Studies using skin fibroblasts derived from patients with neurodegenerative disorders demonstrate that cell stress pathways and bioenergetics are altered when compared to healthy individuals. However, findings in MS skin fibroblasts are limited. Here, we collected skin fibroblasts from 24 healthy control in...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
In conclusion, the concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate. A Discussion of Recent Work on Allotopic Expression of Mitochondrial Genes at the SENS Research Foundation https://www.fightaging.org/archives/2020/02/a-discussion-of-recent-work-on-allotopic-expression-of-mitochondrial-genes-at-the-sens-research-foundation/ A paper published last month outlines recent progress on allotopic expression of mitochondrial genes carried out by the SENS Research ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study provides novel insight into genetic determinants of poor outcomes after acute injury to the neonatal brain and how early-life brain injury can influence adult-onset neurodegenerative disease during aging.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Albert Sanfeliu1, Karsten Hokamp2, Michael Gill1 and Daniela Tropea1,3*1Neuropsychiatric Genetics, Department of Psychiatry, School of Medicine, Trinity Translational Medicine Institute, St James Hospital, Dublin, Ireland2Department of Genetics, School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland3Department of Psychiatry, School of Medicine, Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, IrelandRett syndrome is a rare neuropsychiatric disorder with a wide symptomatology including impaired communication and movement, cardio-respiratory abno...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Conclusion The key problem with the ND field is the lack of understanding in the events preceding the development of protein-based markers – such as Tau – currently used to diagnose NDs. By this stage, the diseases become more difficult to treat. SncRNAs play an important regulatory role in the maintenance of the homeostatic brain. Therefore, changes in their concentration levels can be indicative of mechanistic changes that could precede protein-based markers. One single sncRNA biomarker is unlikely to differentiate between diseases. However, a combination of sncRNA biomarkers could be illustrative of the me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions Stroke comprises ischemic stroke and ICH. The immuno-inflammatory process is involved in neural plasticity following events such as a hemorrhage or ischemic stroke. After ischemia, astrocytes, microglia, and MDMs play important roles during rehabilitation with the modulation of cytokines or chemokines, such as TNF-α and IL-1. Moreover, MiRNAs are also important posttranscriptional regulators in these glial mitochondrial responses to cerebral ischemia. ICH involves processes similar and different to those seen in ischemia, including neuronal injury, astrocytic and microglial/macrophage activation, and neu...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes. Intron Retention via Alternative Splicing as a Signature of Aging https://www.fightaging.org/archives/2019/03/intron-retention-via-alternative-splicing-as-a-signature-of-aging/ In recent years researchers have inv...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, this is the first report to show that pyroptotic cell death occurs in the aging brain and that the inflammasome can be a viable target to decrease the oxidative stress that occurs as a result of aging. Reducing Levels of Protein Manufacture Slows Measures of Aging in Nematodes https://www.fightaging.org/archives/2018/12/reducing-levels-of-protein-manufacture-slows-measures-of-aging-in-nematodes/ Researchers here demonstrate that an antibiotic slows aging in nematode worms, providing evidence for it to work through a reduction in protein synthesis. Beyond a slowing of aging, one of the con...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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