Challenges in the Development of Drugs for Sarcopenia and Frailty - Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force

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Abstract

Sarcopenia and frailty represent two burdensome conditions, contributing to a broad spectrum of adverse outcomes. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually in September 2021 to discuss the challenges in the development of drugs for sarcopenia and frailty. Lifestyle interventions are the current mainstay of treatment options in the prevention and management of both conditions. However, pharmacological agents are needed for people who do not respond to lifestyle modifications, for those who are unable to adhere, or for whom such interventions are inaccessible/unfeasible. Preliminary results of ongoing trials were presented and discussed. Several pharmacological candidates are currently under clinical evaluation with promising early results, but none have been approved for either frailty or sarcopenia. The COVID-19 pandemic has reshaped how clinical trials are conducted, in particular by enhancing the usefulness of remote technologies and assessments/interventions.

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Sarcopenia: revised European consensus on definition and diagnosis

Alfonso Cruz-Jentoft, Gulistan Bahat, Jürgen Bauer … (2018)

Abstract Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.

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A global clinical measure of fitness and frailty in elderly people.

Kenneth Rockwood, Xiaowei Song, Chris MacKnight … (2005)

There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. The CSHA Clinical Frailty Scale was highly correlated (r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%-30.6%) and entry into an institution (23.9%, 95% CI 8.8%-41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.

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Frailty consensus: a call to action.

John E. Morley, Bruno Vellas, G van Kan … (2013)

Frailty is a clinical state in which there is an increase in an individual's vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. 1. Physical frailty is an important medical syndrome. The group defined physical frailty as "a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual's vulnerability for developing increased dependency and/or death." 2. Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy. 3. Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons. 4. For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (>5%) due to chronic disease should be screened for frailty. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

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Contributors

Matteo Cesari: macesari@gmail.com

Journal

Journal ID (nlm-ta): J Frailty Aging

Journal ID (iso-abbrev): J Frailty Aging

Title: The Journal of Frailty & Aging

Publisher: Springer International Publishing (Cham )

ISSN (Print): 2260-1341

ISSN (Electronic): 2273-4309

Publication date (Electronic): 1 April 2022

Publication date PMC-release: 1 April 2022

Publication date (Print): 2022

Volume: 11

Issue: 2

Pages: 135-142

Affiliations

[1 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, , University of Milan (UNIMI), ; Via Camaldoli 64, 20138 Milano, Italy

[2 ]Department of Aging, Neurology, Orthopedic della Testa-Collo, Agostino Gemelli Policlinic Foundation, Roma, Italy

[3 ]GRID grid.411175.7, ISNI 0000 0001 1457 2980, Gérontopôle, , CHU Toulouse, ; Toulouse, France

[4 ]GRID grid.508992.f, ISNI 0000 0004 0601 7786, Nutrition, Exercise Physiology, and Sarcopenia Laboratory, , Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, ; Boston, MA USA

[5 ]GRID grid.418424.f, ISNI 0000 0004 0439 2056, Translational Medicine, , Novartis Institutes for Biomedical Research Inc., ; Cambridge, USA

[6 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, Biophytis, , Université Pierre et Marie Curie, ; Paris, France

[7 ]Longeveron Inc., Miami, USA

[8 ]GRID grid.38142.3c, ISNI 000000041936754X, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women’s Hospital, , Harvard Medical School, ; Boston, USA

Article

Publisher ID: 141

DOI: 10.14283/jfa.2022.30

PMC ID: 9017069

PubMed ID: 35441189

SO-VID: 99357dcc-8276-405f-9fdd-befd7ec89f94

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Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

History

Date received : 10 February 2022

Date accepted : 13 March 2022

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Keywords: aging,pharmacological interventions,physical performance,clinical trial,sarcopenia,frailty

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Keywords: aging, pharmacological interventions, physical performance, clinical trial, sarcopenia, frailty

Challenges in the Development of Drugs for Sarcopenia and Frailty - Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force

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Novel Coronavirus Disease COVID-19

Most cited references 42

Sarcopenia: revised European consensus on definition and diagnosis

A global clinical measure of fitness and frailty in elderly people.

Frailty consensus: a call to action.

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