Clinical trials of disease-modifying therapies for neurodegenerative diseases: the challenges and the future

2010 ◽  
Vol 16 (11) ◽  
pp. 1223-1226 ◽  
Author(s):  
Anthony E Lang
Keyword(s):  
Clinical Trials ◽  
Neurodegenerative Diseases ◽  
Disease Modifying Therapies ◽  
The Future ◽  
Disease Modifying

Does protein aggregation drive postmitotic tissue degeneration?

2021 ◽  
Vol 13 (577) ◽  
pp. eaax0914 ◽  
Author(s):  
Jeffery W. Kelly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Protein Aggregation ◽  
Protein Aggregate ◽  
Tissue Degeneration ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Amyloid Diseases ◽  
Aggregate Structures

Pharmacological evidence, from clinical trials where patients with systemic amyloid diseases are treated with disease-modifying therapies, supports the notion that protein aggregation drives tissue degeneration in these disorders. The protein aggregate structures driving tissue pathology and the commonalities in etiology between these diseases and Alzheimer’s disease are under investigation.

REPORT FROM THE FIRST CLINICAL TRIALS ON ALZHEIMER’S DISEASE (CTAD) ASIA-CHINA 2018 : BRINGING TOGETHER GLOBAL LEADERS

2019 ◽  
pp. 1-4
Author(s):  
J.K. Chhetri ◽  
P. Chan ◽  
B. Vellas ◽  
J. Touchon ◽  
S. Gauthier
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Chinese Population ◽  
The West ◽  
Disease Modifying Therapies ◽  
Increased Risk ◽  
Disease Modifying ◽  
Past Experiences

Population of older adults in Asia, and particularly in China is increasing rapidly. Older population are at increased risk of Alzheimer’s disease (AD) and other dementias. Soon, the Chinese population with AD will represent almost half of the world’s AD population. There is a desperate need of disease modifying therapies to delay or slow the progression of AD, to tackle this emerging healthcare emergency. In this context, the first CTAD Asia-China conference was held in China to bring together Western and Asian leaders in AD. This meeting focused largely on how to develop successful trials in China, utilizing past experiences from the West.

scholarly journals Disease-Modifying Therapies in Type 1 Diabetes: A Look into the Future of Diabetes Practice

Drugs ◽  
2019 ◽  
Vol 79 (1) ◽  
pp. 43-61 ◽  
Author(s):  
Carla Greenbaum ◽  
Dana VanBuecken ◽  
Sandra Lord
Keyword(s):  
Type 1 Diabetes ◽  
Disease Modifying Therapies ◽  
The Future ◽  
Disease Modifying

scholarly journals Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials

2020 ◽  
Vol 13 ◽  
pp. 175628642096901
Author(s):  
Yinan Zhang ◽  
Natalia Gonzalez Caldito ◽  
Afsaneh Shirani ◽  
Amber Salter ◽  
Gary Cutter ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Disease Activity ◽  
Meta Analysis ◽  
Group Level ◽  
T2 Lesions ◽  
Disease Modifying Therapies ◽  
Level Data ◽  
Disease Modifying ◽  
Magnetic Resonance Imaging Mri

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing–remitting MS (RRMS). Methods: DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new T2 lesions, and gadolinium-enhanced lesions on MRI. Using the mean baseline patient age from each trial, a weighted linear regression was fitted to determine whether age was associated with treatment efficacy on a group level. Results: Group-level data from a total of 28,082 patients from 26 trials of 14 different DMTs were included in the meta-analysis. There were no statistically significant associations between age and reductions in ARR, new T2 lesions, and gadolinium-enhanced lesions of the treatment group compared with placebo. Conclusion: DMTs for RRMS show efficacy in treating disease activity independent of age as demonstrated by group-level data from DMT clinical trials. Nevertheless, clinical trials select for patients with baseline disease activity regardless of age, thereby not representing real-world patients with RRMS, where disease activity declines with age.

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.

scholarly journals Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Wojciech Kozubski ◽  
Kevin Ong ◽  
Wioletta Waleszczyk ◽  
Matthew Zabel ◽  
Jolanta Dorszewska
Keyword(s):  
Synaptic Plasticity ◽  
Neurodegenerative Diseases ◽  
Learning And Memory ◽  
Neural Plasticity ◽  
Lewy Bodies ◽  
Brain Diseases ◽  
Memory And Learning ◽  
Disease Modifying Therapies ◽  
Disease Modifying

Neural plasticity—the ability to alter a neuronal response to environmental stimuli—is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer’s disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases. While vascular lesions are the principal cause of VaD, neurodegenerative processes have been established as etiological agents of many dementia diseases. Chief among such processes is the deposition of pathological protein aggregates in vivo including β-amyloid deposition in AD, the formation of neurofibrillary tangles in AD and FTD, and the accumulation of Lewy bodies composed of α-synuclein aggregates in DLB and PDD. The main symptoms of dementia are cognitive decline and memory and learning impairment. Nonetheless, accurate diagnoses of neurodegenerative diseases can be difficult due to overlapping clinical symptoms and the diverse locations of cortical lesions. Still, new neuroimaging and molecular biomarkers have improved clinicians’ diagnostic capabilities in the context of dementia and may lead to the development of more effective treatments. Both genetic and environmental factors may lead to the aggregation of pathological proteins and altered levels of cytokines, such that can trigger the formation of proinflammatory immunological phenotypes. This cascade of pathological changes provides fertile ground for the development of neural plasticity disorders and dementias. Available pharmacotherapy and disease-modifying therapies currently in clinical trials may modulate synaptic plasticity to mitigate the effects neuropathological changes have on cognitive function, memory, and learning. In this article, we review the neural plasticity changes seen in common neurodegenerative diseases from pathophysiological and clinical points of view and highlight potential molecular targets of disease-modifying therapies.

Translational research on disease-modifying therapies for neurodegenerative diseases

2013 ◽  
Vol 1 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Masahisa Katsuno ◽  
Hirohisa Watanabe ◽  
Fumiaki Tanaka ◽  
Gen Sobue
Keyword(s):  
Neurodegenerative Diseases ◽  
Translational Research ◽  
Disease Modifying Therapies ◽  
Disease Modifying
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