Sean M. Healey & AMG Center for ALS

MESSAGE FROM THE DIRECTOR

Greetings from the ALS Multidisciplinary Clinic in the Sean M. Healey & AMG Center for ALS at Mass General,

We started 2024 with exciting research from the bench that reveals new mechanisms of ALS biology. We are confident these new discoveries will open the door to many new therapeutic targets and treatments. Our goal and focus is to translate the most promising discoveries into therapies that can be tested in people with ALS in clinical trials while also providing personalized, accessible care to improve the quality of life of individuals who are living with ALS today.

Our ability to move quickly is made possible by your continued support. We are thrilled to announce an exciting opportunity to match gifts we receive to support our rapid ALS drug platform screening and evaluation program. We have been offered to match up to $1.3 million, which will provide a major boost and allow to expand our search for effective therapies while reaching more people living with ALS.

Your continued advocacy and support of this work keeps us going.

Thank you for staying with us on this journey. Together, we will find the cures.

Warmly,

Merit Cudkowicz, MD, MSC

From the Bench: Latest in ALS Research

At the Sean M. Healey & AMG Center for ALS, we are dedicated to leading the charge to cure ALS through innovation and research. Our labs in Charlestown, MA are the scientific hub of our center, where our team works tirelessly to advance our studies and develop treatments for ALS and other neurodegenerative diseases. We are excited to announce that we received a major grant from the National Institute of Neurological Disorders and Stroke (NINDS) to fund a bold, new initiative from the team of Clotilde Lagier-Tourenne, MD, PhD. In addition, our leading ALS research scientists have made breakthroughs in their work understanding molecular mechanisms, biomarkers and genetics in ALS.

NINDS Awards Collaborative Opportunities for Multidisciplinary, Bold, and Innovative Neuroscience (COMBINE) Program Grant

Dr. Lagier-Tourenne’s team and her collaborators at the Broad Institute and at the NINDS will receive funding for their project, “Targeting Dysregulated RNA Splicing in Neurodegenerative Diseases.” This groundbreaking study will provide new insight into the intricate cellular mechanisms of ALS and offer a clearer understanding of the molecular events leading to the onset and progression of the disease.

This information will allow the team to identify potential targets for drug therapy, by understanding how RNA-binding proteins (RBPs) such as TDP-43 are dysfunctional in different cell types (neurons and immune cells) of the brain. Indeed, several RBPs are abnormally aggregated in cells from people with ALS leading to aberrant processing of RNAs and errors in their splicing (which is a maturation step of the RNAs). The three labs will collaborate to apply new technologies that make it possible for the first time to comprehensively track the abnormal splicing events occurring in ALS, and to identify genetic modulators that correct this process.

These awards support multidisciplinary teams that seek to cross technical and conceptual boundaries through interdisciplinary collaboration to achieve a single, focused, and transformative goal. To learn more about the program, visit the website

Understanding Molecular Mechanisms in Neurodegenerative Diseases

The lab of Dr. Clotilde Lagier-Tourenne works to develop new therapeutic strategies that target molecular mechanisms. Recently, they published three manuscripts on the importance of restoring the Stathmin-2 (STMN2) protein to restore function in people with ALS (pALS) and those with dementia. These manuscripts can be found here.

A Team Effort to Accelerate ALS Drug Development

The HEALEY ALS Platform Trial continues to be the leading clinical trial in ALS research. We are testing seven investigational products (potential therapies) across Regimens A-G with over 1,400 participants and look forward to adding new therapies. Two of the first four therapies are moving forward in Phase 3 studies (CNM-AU8 and Pridopidine). Two of the therapies are currently actively enrolling participants; Regimen F testing ABBV-CLS-7262 by Calico Life Sciences in collaboration with AbbVie Inc. and Regimen G testing DNL343 by Denali Therapeutics.

HEALEY ALS Platform Trial Q&A Webinar

Please join us every Thursday for our weekly updates on the platform trial at 5:00 pm EST (4:00 pm CST/2:00 pm PST) scan the QR code to register.

A generous donor will match up to $1.3 million in philanthropic support toward this effort, which will allow us to build on this success. We are adding two innovative trial features to further accelerate, target, and improve how treatments are developed for people with ALS:

1. greatly expand the biomarkers tested in the HEALEY ALS Platform trial and

2. accelerate the pace of participant enrollment.

Expanding Biomarkers to Accurately Measure ALS:

Our ability to slow, repair and prevent ALS depends on accurate measurements of disease. Biomarkers measured in biofluids, as well as digital data, are revealing the fundamental biology of ALS and quantifying functional changes people with ALS experience. These details will improve our ability to diagnosis ALS accurately and earlier. We must accelerate our efforts to identify more biomarkers. The HEALEY ALS Platform Trial can serve as an efficient and effective tool to accomplish this goal.

Expanding Participation in ALS Clinical Trials:

The HEALEY ALS Platform Trial has accelerated the launch of clinical trials and expanded access to more individuals, but bottlenecks around enrollment continue. To accelerate enrollment, broaden access, and get answers faster, we plan to launch Centers for Clinical Trial Excellence, providing training and salary support for top clinical trial coordinators and site investigators – Nurse Practitioners or Medical Doctors. Our initial goal is to triple the speed of participant enrollment. These “super enroller sites” will allow individuals to join every day, eliminating delays in study launches so that we can move more clinical trials forward quickly. No person with ALS will be told again that they need to wait to participate in a trial!

Thank you in advance for considering supporting this effort. If you have questions or would like to learn more about how you can support this effort, please contact Emily Monteiro at emonteiro7@mgh.harvard.edu.

Other Clinical Trials and Clinical Research: Latest Updates

34th Annual MND Symposium

The 34th annual MND Symposium was held in December in Basel, Switzerland. Drs. Jeremy Shefner (Barrow Neurological Institute) and Ben Saville (Berry Consultants) presented the latest updates from the HEALEY ALS Platform Trial. Dr. Saville presented on the joint model of function and survival, which is implemented in the Platform Trial, and Dr. Shefner discussed the results from the trial of Pridopidine (regimen D). The results from Regimen D, initially released in February of 2023, did not meet the criterion on the primary outcome measures, however, we found significant improvements in regard to speech and bulbar function, as well as overall function in those earlier in the disease course. Dr. Shefner provided insight on these encouraging findings and discussed the ongoing open-label extension and planned phase III study. Dr. Cudkowicz presented the long-term follow-up date from the toferson (qalsody) study in people with ALS from mutations in SOD1, including updates that a significant number of participants had improvement in strength and function. Additionally, Dr. Suma Babu shared results of a double-blind, placebo-controlled clinical trial of AIT-10.

The 5th annual Sean M. Healey International Prize for Innovation in ALS and 3rd annual Drs. Ayeez and Shelena Lalji & Family ALS Endowed Award for Innovative Healing were also presented in celebration of the most innovative research advance in ALS.

The NADALS Basket Trial

The Neurodegenerative Alzheimer’s Disease and Amyotrophic Lateral Sclerosis (NADALS) study is testing the FDA-approved drug baricitinib (used to treat rheumatoid arthritis) to see if it reduces inflammation in individuals with either Alzheimer’s disease or ALS. Although the trial is

expected to continue through December 2024, Dr. Albers and his team have already learned a great deal about how the drug affects the nervous system and how well it accesses the brain and are eager to determine if it reduces inflammation or neurodegeneration link.

Learn more

Access for ALL in ALS (ALL ALS)

The NIH established a transformative national ALS clinical research consortium called Access for All in ALS (ALL ALS). This new consortium is a multi-institutional effort to accelerate research discoveries in ALS. The consortium is led by principal investigators at the Healey & AMG Center for ALS, the Barrow Neurological Institute, and Columbia University.

Extending Experimental Therapy Access

We are proud to be leaders in ensuring that as many people with ALS (PALS) as possible have access to experimental drugs that are based on great science.

ACT for ALS NIH Grants for Expanded Access

The Healey & AMG Center at Mass General was awarded three grants from the National Institutes of Health (NIH) to support Expanded Access Protocol Programs at over 45 centers across the country

Learn more

Never Surrender Inc Awards Grant to Launch Two New EAP Sites in Minnesota

Never Surrender Inc has made a gift to the Healey & AMG Center to establish two new Expanded Access Protocol (EAP) Program sites in Minnesota. Establishing these sites will allow access to experimental treatments for pALS in the state of Minnesota and surrounding areas, as well as the collection of safety and biomarker data.

News From Our Clinic

Daniella Lipper ALS House Call and ALS Parenting at a Challenging Time Programs

The Healey & AMG Center is thrilled to share that the EGL Charitable Foundation has generously endowed the ALS House Call and ALS Parenting at a Challenging Time (PACT) Programs, named in honor of Daniella Lipper.

In the Community

rivALS Teaming Up to Raise Funds for ALS

Through the Tackle ALS campaign, a partnership between former NFL player, Tim Green and his family and the Healey & AMG Center, the Atlanta Falcons and New Orleans Saints partnered to host two special “rivALS” games in both of their NFL matchups this season (11/26 and 1/7). There was a 50/50 raffle at each game, with partial proceeds benefitting Tackle ALS. A total of $300,000 was raised which will go towards our new repair and regeneration initiative, focused on developing therapies that repair or reverse damage caused by ALS and ultimately preventing the disease entirely.

Impact of Philanthropy

Our work at the Sean M. Healey & AMG Center for ALS combines outstanding, multidisciplinary care with clinical and basic research informed by the needs of our patients. Philanthropy allows us to accelerate the pace of discovery and make a meaningful difference to our patients and their families. Your support helps to fuel breakthroughs and discoveries in the field of ALS and ensure everyone with ALS can access effective treatments and therapies We are determined to find the cures and we are confident your partnership will get us there. Thank you for your consideration.

If you have questions or would like to learn more about how you can support the Sean M. Healey & AMG Center for ALS, please contact Emily Monteiro at emonteiro7@mgh.harvard.edu or visit https://www.massgeneral.org/neurology/als/support/.

on our clinical programs and research initiatives.