Living with ALS

_____

Alan I. Leshner, Rebecca A. English, and Joe Alper, Editors

Committee on Amyotrophic Lateral Sclerosis:
Accelerating Treatments and Improving Quality of Life

Board on Health Care Services

Board on Health Sciences Policy

Health and Medicine Division

Consensus Study Report

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This activity was supported by a contract between the National Academy of Sciences and the National Institute of Neurological Disorders and Stroke, National Institutes of Health (contract number HHSN263201800029I, task order 75N98022F00011). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-71801-1
International Standard Book Number-10: 0-309-71801-5
Digital Object Identifier: https://doi.org/10.17226/27739
Epub ISBN: 978-0-309-71804-2

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2024. Living with ALS. Washington, DC: The National Academies Press. https://doi.org/10.17226/27739.

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COMMITTEE ON AMYOTROPHIC LATERAL SCLEROSIS: ACCELERATING TREATMENTS AND IMPROVING QUALITY OF LIFE

ALAN I. LESHNER (Chair), Chief Executive Officer, Emeritus, American Association for the Advancement of Science (retired)

SUMA BABU, Assistant Professor of Neurology, Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital, Harvard Medical School; Co-Director, Neurological Clinical Research Institute, Massachusetts General Hospital

CHELSEY R. CARTER, Assistant Professor of Public Health, Yale University

MACEO CARTER, Person living with ALS

GEORGE DEMIRIS, Penn Integrates Knowledge University Professor, University of Pennsylvania

JOHN DUNLOP, Chief Scientific Officer, Aliada Therapeutics

EVA L. FELDMAN, James W. Albers Distinguished University Professor, University of Michigan; Director, NeuroNetwork for Emerging Therapies and ALS Center of Excellence

HOLLY FERNANDEZ LYNCH, Assistant Professor of Medical Ethics and Law, University of Pennsylvania

ILEANA HOWARD, Medical Co-Director, ALS Center of Excellence, VA Puget Sound, Veterans Health Administration

JEROME E. KURENT, Professor of Neurology and Medicine, Medical University of South Carolina; Ralph H. Johnson Veterans Affairs Medical Center ALS Interdisciplinary Clinic

WON YOUNG LEE, Associate Professor of Pulmonary, Critical Care, and Sleep Medicine, University of Texas Southwestern Medical Center

HAROLD L. PAZ, Operating Partner, Khosla Ventures

TONYA J. ROBERTS, Associate Professor, University of Wisconsin–Madison

RITA SATTLER, Professor of Translational Neuroscience, Barrow Neurological Institute

JOEL SHAMASKIN, Person living with ALS; Professor Emeritus of Medicine, University of Rochester School of Medicine and Dentistry (retired)

JOSHUA SHARFSTEIN, Professor of the Practice, Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health

ANANTHA SHEKHAR, Senior Vice Chancellor for the Health Sciences, John and Gertrude Petersen Dean, School of Medicine, University of Pittsburgh

MINDY UHRLAUB, Author and familial ALS activist; member, Peer Mentor Team and Familial ALS Team at I AM ALS; founding member, Genetic ALS & FTD: End the Legacy

Study Staff

REBECCA A. ENGLISH, Study Director

ASHLEY BOLOGNA, Senior Program Assistant

LYLE CARRERA, Research Associate

SHARYL NASS, Senior Director, Board on Health Care Services

CLARE STROUD, Senior Director, Board on Health Sciences Policy

Consultants

JOE ALPER, Science writer

SARAH LUNSFORD, Public engagement consultant

Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

JINSY ANDREWS, Columbia University

LORA CLAWSON, Johns Hopkins University School of Medicine

MARY CATHERINE COLLET, Independent ALS advocate

KULDIP DAVE, ALS Association

GREGG GONSALVES, Yale University

JOHN HANSEN-FLASCHEN, University of Pennsylvania

KATHLEEN U. HOLT, Center for Medicare Advocacy

COLLIN HOVINGA, Critical Path Institute

STORY LANDIS, National Institute of Neurological Disorders and Stroke (retired)

NANCY LEAMOND, AARP

JEAN SWIDLER, Genetic ALS & FTD: End the Legacy

NETA ZACH, Takeda

BERNIE ZIPPRICH, Healthcare innovation expert and person living with ALS

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by JONATHAN M. SAMET, Colorado School of Public Health, and DAN G. BLAZER II, Duke University School of Medicine. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Acknowledgments

The committee and project staff extend their gratitude to the many people and organizations who were critical in supporting and informing the committee’s work. This study was sponsored by the National Institutes of Health (NIH) and, in particular, was supported by the National Institute of Neurological Diseases and Stroke (NINDS). The committee thanks NIH and NINDS for their support, and the committee thanks Congress for initiating this important study.

People with amyotrophic lateral sclerosis (ALS), their caregivers and family members, representatives of ALS nonprofit organizations, researchers, and clinicians graciously offered their expertise and perspectives throughout the study process. This information was not only useful but also courageous, heartfelt, and inspiring. The committee heard from many people in different ways throughout the study and would like to extend its appreciation to each.

Over the course of its meetings, the committee heard from many people who shared their stories about ALS. This allowed the committee to center their work in the real-world lived experiences of those living with and affected by this disease, as well as to gain valuable insight as to the challenges and opportunities faced by those who fight against ALS in their daily lives, at labs or clinics, and alongside countless community organizations. The committee thanks the many participants in its public sessions: Lori Banker-Horner, James Berry, Sunny Brous, Katrina Byrd, Nora Capocci, Blair Casey, Jim Clingman, Sylvia Clingman, Cathy Collet, Norah Crossnohere, Penny Dacks, Dan Doctoroff, Sonya Elling, Ron Faretra, Albert Faro, Sarah Fontaine, Renee Golden, John

Hansen-Flaschen, Bob Hebron, Terry Heiman-Patterson, Colleen Hoarty, Collin Hovinga, Justin Ichida, Vanessa Jackson, Asia Jami, Desiree Galvez Kessler, Lisa Latts, Ashley Lee, Melanie Lendnal, Joanne Lynn, Paul Mehta, Paul Melmeyer, Indu Navar, Siobhan Pandya, Juliet Pierce, Terri Postma, Kristin Rankin, Julian Rodriguez, Bruce Rosenblum, Paul Seifert, Jean Swidler, Neil Thakur, Fernando Vieira, and William Woods.

The committee also benefited from the perspectives of six individuals appointed as lived experience consultants (volunteers). The lived experience consultants provided reflections on some excerpts of draft report text between January and March 2024. The committee expresses its gratitude to Michael Cosgray, Desiree Galvez Kessler, Bernadine A. Okeke, Ann Oliff, Kristin Rankin, and Julian (Jules) Rodriguez for their participation in the study process as lived experience consultants.

The committee also thanks Sarah Lunsford, who served as a consultant to organize many of these public engagement opportunities.

The staff of the National Academies of Sciences, Engineering, and Medicine contributed in many ways throughout the study process. The committee extends its sincerest gratitude to the study team for their hard work and dedication throughout this project: Rebecca A. English, Lyle Carrera, and Ashley Bologna. The committee is grateful for the many staff within the Health and Medicine Division who provided support for the project. Special thanks are extended to Christie Bell, senior financial business partner; Lori Brenig, editorial projects coordinator; and Mark Goodin for his editorial assistance in preparing the report.

Contents

ACRONYMS AND ABBREVIATIONS

PREFACE

SUMMARY

1 INTRODUCTION AND STUDY CONTEXT

Epidemiology

Study Task

The Nature of ALS and Its Symptoms

Study Approach and Scope

References

2 LIVING WITH ALS TODAY

Making ALS Livable in 10 Years

Racial Inequities in ALS Diagnosis, Care, and Outcomes

Concluding Comments

References

3 MAKING ALS LIVABLE IN THE NEAR TERM

Insurance Challenges

Inadequate Home Services

High Out-of-Pocket Costs

Supporting Caregivers

Respiratory Management of ALS

References

4 CREATING A SUSTAINABLE AND ACCESSIBLE ALS CLINICAL CARE AND RESEARCH SYSTEM

ALS Multidisciplinary Care

Integrating Clinical Research into the ALS Care Delivery Network

Building the Ideal ALS Care Delivery System

ALS Care System Challenges

References

5 ADVANCING ALS RESEARCH AND ACCELERATING THERAPEUTIC DEVELOPMENT

ALS Drug Development Through the Years

ALS Clinical Trials and Natural History Studies

Developing ALS Biomarkers and Other Clinical Endpoints to Serve as Indicators of Drug Efficacy

Trade-offs in ALS Drug Development and Approval

Establishing a Comprehensive ALS Registry

New and Emerging Nonpharmacological Technologies

References

6 PREVENTING ALS

Identifying At-Risk Genetic Carriers

Nongenetic Factors and Prevention

References

APPENDIXES

A Public Session Agendas

B Biographical Sketches of Committee Members and Staff

C Disclosure of Unavoidable Conflicts of Interest

Boxes, Figures, and Tables

BOXES

1-1 Statement of Task

1-2 Lived Experience Consultants

2-1 Perspectives on Living with ALS

2-2 Caregiver Views on Quality of Life

2-3 Action List for the ALS Community

2-4 Diagnostic Delay in ALS

3-1 Perspectives from Caregivers of People Living with ALS

4-1 ALSA Certification Process for Treatment Centers of Excellence

4-2 Specialty Care Medical Home: A Model for Coordinating Community-Based Multidisciplinary Care for ALS

5-1 Types of Biomarkers

5-2 Registries and Natural History Studies

5-3 National ALS Registry Data Needs

FIGURES

1-1 Most common ALS subtypes, natural history, and multidisciplinary treatment

Acronyms and Abbreviations

Preface

Amyotrophic lateral sclerosis (ALS) is a terrible, inevitably fatal disease. Receiving a diagnosis of ALS is devastating for people living with ALS, their families, and their caregivers. Dealing with this illness requires a complex array of medical and support service interventions, and the intensity of care required increases exponentially over time. This report lays out an agenda that, if implemented, would provide greater and more equitable access to state-of-the-art multidisciplinary care, accelerate the development of more effective treatments, improve the quality of life and health of those individuals suffering from the illness both now and in the future, and provide better support for their families and caregivers. Implementing this agenda would go far toward the goal set in the committee’s charge of making ALS a livable disease within a decade.

This consensus report is the product of a committee of scientific and clinical experts from a variety of fields, as well as individuals living with the disease and people at clear risk for developing it. In addition, the committee met with a variety of other people living with the illness and asked them to reflect on the relevance of the committee’s thinking and its potential recommendations. Including these individuals in our work helped greatly to ground the committee’s work in real-life experiences and, I believe, significantly improved both the quality of this report and the appropriateness of its recommendations.

As discussed in the report, the committee was aware that at the same time it was working on this project, many other, often parallel projects with similar goals were ongoing. We tried to remain cognizant of those efforts in framing our report and recommendations so as to avoid inadvertent conflicts or excessive duplication in strategies for accomplishing our shared goals.

Achieving the vision underlying this report will require commitment and leadership from many different stakeholders. Some of the report’s recommendations require substantial resources, but their impacts will be great for the more than 30,000 individuals living with ALS and the thousands more who are at clear risk of developing the disease. The steps recommended here include developing a comprehensive multidisciplinary care and research network that would do much to ensure substantially more equitable access to state-of-the-art care for all individuals with ALS, reduce unacceptably long delays in receiving an accurate diagnosis, significantly expand the research infrastructure needed to develop new and improved treatments and support services, and explore new ways to help finance appropriate care and supports. As with all endeavors with grand goals, achieving the agenda laid out here will not only require substantial resources and leadership from a variety of stakeholders, but these diverse groups will have to come together with a common focus and consistent messages about what is needed to make real progress against this dreaded disease.

I am extremely grateful to my colleagues on the National Academies of Sciences, Engineering, and Medicine committee that authored this report. It was both an honor and a pleasure to work with them all. I also want to express, on behalf of the whole committee, our gratitude to the exceptionally competent and dedicated staff of the National Academies, led by the study director, Rebecca English, and the many others cited in the acknowledgments.

Alan I. Leshner, Chair

Committee on Amyotrophic Lateral Sclerosis: Accelerating Treatments and Improving Quality of Life