scholarly journals Critical Appraisal of Amyloid Lowering Agents in AD

2021 ◽  
Vol 21 (8) ◽  
Author(s):  
Boris Decourt ◽  
Fadel Boumelhem ◽  
Evans D. Pope ◽  
Jiong Shi ◽  
Zoltan Mari ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Drug Approval ◽  
Final Decision ◽  
Valuable Insight ◽  
Future Directions ◽  
Avant Garde ◽  
Aβ Aggregation ◽  
Disease Modifying ◽  
Disease Modifying Agents ◽  
Amyloid Cascade

Abstract Purpose of Review According to the amyloid cascade hypothesis, removing amyloid beta (Aβ) should cure Alzheimer’s disease (AD). In the past three decades, many agents have been tested to try to lower Aβ production, prevent Aβ aggregation, and dissolve Aβ deposits. However, the paucity in definitive preventative or curative properties of these agents in clinical trials has resulted in more avant-garde approaches to therapeutic investigations. Immunotherapy has become an area of focus for research on disease-modifying therapies for neurodegenerative diseases. In this review, we highlight the current clinical development landscape of monoclonal antibody (mAb) therapies that target Aβ plaque formation and removal in AD. Recent Findings Multiple potential disease-modifying therapeutics for AD are in active development. Targeting Aβ with mAbs has the potential to treat various stages of AD: prodromal, prodromal to mild, mild, and mild to moderate. Monoclonal antibodies discussed here include aducanumab, lecanemab, solanezumab, crenezumab, donanemab, and gantenerumab. Summary The final decision by the FDA regarding the approval of aducanumab will offer valuable insight into the trajectory of drug development for mAbs in AD and other neurodegenerative diseases. Future directions for improving the treatment of AD will include more inquiry into the efficacy of mAbs as disease-modifying agents that specifically target Aβ peptides and/or multimers. In addition, a more robust trial design for AD immunotherapy agents should improve outcomes such that objective measures of clinical efficacy will eventually lead to higher chances of drug approval.

scholarly journals She Doesn’t Even Go Here: The Role of Inflammatory Astrocytes in CNS Disorders

2021 ◽  
Vol 15 ◽  
Author(s):  
Jacqueline Kelsey Reid ◽  
Hedwich Fardau Kuipers
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Therapeutic Targeting ◽  
Future Directions ◽  
Cns Disorders ◽  
Disease Modifying Therapies ◽  
Astrocyte Heterogeneity ◽  
Disease Modifying ◽  
Innovative Techniques

Astrocyte heterogeneity is a rapidly evolving field driven by innovative techniques. Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are present in a variety of neurodegenerative diseases and may play a role in their pathogenesis. Moreover, genetic and therapeutic targeting of these astrocytes ameliorates disease in several models, providing support for advancing the development of astrocyte-specific disease modifying therapies. This review aims to explore the methods and challenges of identifying inflammatory astrocytes, the role these astrocytes play in neurological disorders, and future directions in the field of astrocyte heterogeneity.

Phenotypic Screens Targeting Neurodegenerative Diseases

2013 ◽  
Vol 19 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Minhua Zhang ◽  
Guangrui Luo ◽  
Yanjiao Zhou ◽  
Shaohui Wang ◽  
Zhong Zhong
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Phenotypic Screening ◽  
Disease Modifying Therapy ◽  
Medical Need ◽  
Alternative Approach ◽  
Key Characteristics ◽  
Compound Screening ◽  
Disease Modifying ◽  
Disease Modifying Agents

Neurodegenerative diseases affect millions of people worldwide, and the incidences increase as the population ages. Disease-modifying therapy that prevents or slows disease progression is still lacking, making neurodegenerative diseases an area of high unmet medical need. Target-based drug discovery for disease-modifying agents has been ongoing for many years, without much success due to incomplete understanding of the molecular mechanisms underlying neurodegeneration. Phenotypic screening, starting with a disease-relevant phenotype to screen for compounds that change the outcome of biological pathways rather than activities at certain specific targets, offers an alternative approach to find small molecules or targets that modulate the key characteristics of neurodegeneration. Phenotypic screens that focus on amelioration of disease-specific toxins, protection of neurons from degeneration, or promotion of neuroregeneration could be potential fertile grounds for discovering therapeutic agents for neurodegenerative diseases. In this review, we will summarize the progress of compound screening using these phenotypic-based strategies for this area, with a highlight on unique considerations for disease models, assays, and screening methodologies. We will further provide our perspectives on how best to use phenotypic screening to develop drug leads for neurodegenerative diseases.

scholarly journals Genetic and Transcriptomic Biomarkers in Neurodegenerative Diseases: Current Situation and the Road Ahead

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1030
Author(s):  
Julie Lake ◽  
Catherine S. Storm ◽  
Mary B. Makarious ◽  
Sara Bandres-Ciga
Keyword(s):  
Neurodegenerative Diseases ◽  
Large Scale ◽  
Disease Diagnosis ◽  
Open Science ◽  
Future Directions ◽  
The Road ◽  
Current State ◽  
Molecular Complexity ◽  
Science Framework ◽  
Lateral Sclerosis

Neurodegenerative diseases are etiologically and clinically heterogeneous conditions, often reflecting a spectrum of disease rather than well-defined disorders. The underlying molecular complexity of these diseases has made the discovery and validation of useful biomarkers challenging. The search of characteristic genetic and transcriptomic indicators for preclinical disease diagnosis, prognosis, or subtyping is an area of ongoing effort and interest. The next generation of biomarker studies holds promise by implementing meaningful longitudinal and multi-modal approaches in large scale biobank and healthcare system scale datasets. This work will only be possible in an open science framework. This review summarizes the current state of genetic and transcriptomic biomarkers in Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, providing a comprehensive landscape of recent literature and future directions.

scholarly journals P2-298: Assessing the economic value of potential disease-modifying agents in Alzheimer's disease using simulation

2013 ◽  
Vol 9 ◽  
pp. P467-P467
Author(s):  
Denis Getsios ◽  
Shien Guo ◽  
Nikhil Revankar ◽  
Linus Jonsson ◽  
Peter Neumann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Economic Value ◽  
Disease Modifying ◽  
Disease Modifying Agents
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