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Defining Disease Modifying Therapy for Alzheimer's Disease

Cummings, J; Fox, N; (2017) Defining Disease Modifying Therapy for Alzheimer's Disease. The Journal of Prevention of Alzheimer’s Disease , 4 (2) pp. 109-115. 10.14283/jpad.2017.12. Green open access

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Abstract

BACKGROUND: Disease-modifying therapies (DMTs) are urgently needed to treat the growing number of individuals with Alzheimer's disease (AD) or at immanent risk for AD. A definition of DMT is required to facilitate the process of DMT drug development. PROCESS: This is a review of the state of the science with regard to definition and development of DMTs. RESULTS: A DMT is as an intervention that produces an enduring change in the clinical progression of AD by interfering in the underlying pathophysiological mechanisms of the disease process that lead to cell death. Demonstration of DMT efficacy is garnered through clinical trial designs and biomarkers. Evidence of disease modification in the drug development process is based on trial designs such as staggered start and delayed withdrawal showing an enduring effect on disease course or on combined clinical outcomes and correlated biomarker evidence of an effect on the underlying pathophysiological processes of the disease. Analytic approaches such as showing change in slope of cognitive decline, increasing drug-placebo difference over time, and delay of disease milestones are not conclusive by themselves but support the presence of a disease modifying effect. Neuroprotection is a related concept whose demonstration depends on substantiating disease modification. No single type of evidence in itself is sufficient to prove disease modification - consistency, robustness, and variety of sources of data will all contribute to convincing stakeholders that an agent is a DMT. CONCLUSION: DMT is defined by its enduring effect on processes leading to cell death. A variety of types of data can be used to support the hypothesis that disease modification has occurred.

Type: Article
Title: Defining Disease Modifying Therapy for Alzheimer's Disease
Location: France
Open access status: An open access version is available from UCL Discovery
DOI: 10.14283/jpad.2017.12
Publisher version: https://doi.org/10.14283/jpad.2017.12
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alzheimer’s disease, amyloid, biomarker, disease modifying therapy, staggered start
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10034299
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