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

At the Healey & AMG Center, we continue tirelessly in our quest in the fight against ALS. With a new treatment approved by the FDA and advances in research, we look forward to what is to come as the fall approaches and 2023 comes to a close. 

We were excited to begin administering the new, FDA-approved gene therapy treatment (Qalsody) to our patients with SOD1 ALS. Led by Suma Babu, MD, and Jen Scalia, NP, who quickly established this clinic so that our patients could get it as soon as Qalsody was available, we know this breakthrough will be the first of many to provide new hope for individuals with ALS.



We are channeling our research progress into applications for several new National Institute of Health Grant programs in ALS funded by the new ACT for ALS bill.

At the Healey & AMG Center, we continue to make progress in research and therapy development and we share this knowledge widely.

Thank you again for all you do to raise awareness of and for your active participation in our ALS work. We know that the growing interest in ALS research around the globe, as well as awareness of the urgency of our efforts are increasing thanks to your advocacy and support.

We are so grateful to have you as part of our team. Together we will find the cures.

Warmly,

 Merit Cudkowicz, MD, MSc

HEALEY ALS PLATFORM TRIAL UPDATES

The HEALEY ALS Platform Trial continues to make progress in the fight against ALS. As of September 2023, there are over 1,400 people with ALS enrolled across seven regimens. Results from the initial four investigational products have been shared. Two are moving forward to phase 3 testing (CNM-AU8, Clene Nanomedicine, and Pridopidine, Prilenia). Two others were found ineffective and are not moving forward (Zilucoplan, UCB, and Verdipistat, Biohaven). CNM-AU8 showed benefit in survival at the 30 mg/day dose and delays in key clinical events. Pridopidine demonstrated substantial improvements in speech production, including sustained phonation, speaking rate, articulation rate, and articulatory precision. Results from the fifth regimen (Trehelose, Seelos) are expected by the end of 2023. 

Looking forward, the HEALEY ALS Platform Trial continues to test promising compounds: We dosed the first participant with our sixth investigational product, ABBV-CLS-7262 from Calico Life Sciences in collaboration with AbbVie as well as our seventh compound, DNL-343 from Denali Therapeutics. We continue to enroll individuals in these studies while working with two additional companies to add their compounds in 2024. We prioritize sharing the work that comes out of this trial with our patient, academic, and industry communities, including publications and presentations from team members at the Healey & AMG Center and throughout all collaborating institutions. By broadly sharing our learnings and results, we hope to initiate new studies and breakthroughs that will lead to more effective treatments for people with ALS.

Find the latest list of HEALEY ALS Platform Trial participating sites here.

Sean M. Healey & AMG Center for ALS Announces First Participant Dosed in Regimen G of the HEALEY ALS Platform Trial Evaluating DNL343 by Denali Therapeutics

DNL343 is a novel investigational ALS therapy that aims to target intracellular stress and reduce TDP-43, a protein involved in most forms of ALS and frontotemporal dementia. DNL343 targets eIF2B, a central regulator of the integrated stress response (ISR), which is overactive in ALS, causing a buildup of TDP-43, which leads to neuronal degeneration. In laboratory models inhibition of the ISR by DNL343 dissolves TDP-43 containing stress granules and decreases ISR biomarkers. We look forward to reporting on the results of this compound.  

Earlier this summer as part of the HEALEY ALS Platform Trial Science & Mechanism of Action Webinar Series, Merit Cudkowicz, MD, MSc along with regimen co-lead Suma Babu, MBBS, MPH, and research scientists from Denali Therapeutics, presented the rationale and science behind DNL343, the investigational product being tested in Regimen G of the HEALEY ALS Platform Trial.

Watch the webinar here

Sharing our Research on the HEALEY ALS Platform Trial

We are delighted to announce two papers published in Annals of Neurology, describing the design and biostatistical analysis plan for the Healey ALS Platform Trial: “Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development" and “Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis." These articles are available to download at no cost and we are hoping that by sharing our methods we will inspire more researchers to adopt this platform trial approach.  

Find our full list of publications here

Marianne Chase, the Platform Trial's Director of Operations, was recently interviewed by DPHARM: Disruptive Innovations to Modernize Clinical Research. Marianne discussed the creation and operational aspects of the HEALEY ALS Platform Trial. Read the full article here. Marianne will also be participating in a virtual FDA public meeting, "Mitigating Clinical Study Disruptions during Disasters and Public Health Emergencies" on October 18-19. We will share details on how to join as they become available.

Join our HEALEY ALS Platform Trial #WeeklyWebinar Series!

Healey & AMG Center investigators hold weekly informal Q&A sessions about the HEALEY ALS Platform Trial, as well as monthly comprehensive updates.

See schedule & recordings

Drug Science Webinars 

Below, you can find our most recent drug science webinars, which present the rationale and science behind the investigational products being tested in Regimens F and G of the HEALEY ALS Platform Trial. 

Regimen F- Calico’s ABBV-CLS-7262: Drug Science Webinar

Regimen G- Denali’s DNL343: Drug Science Webinar

EXPANDING ACCESS TO EXPERIMENTAL THERAPIES

At the Healey & AMG Center, we are dedicated to developing effective treatments for ALS and to providing people with ALS access to experimental therapies through our Expanded Access Protocol (EAP) programs. We continue to partner with several stakeholders to create new EAP models for ALS. We are thrilled to have over 400 participants across 26 clinical sites testing 17 investigational products.

Sean M. Healey & AMG Center for ALS and the University of California, Irvine Announce First Participant Enrolled in Expanded Access Protocol Program for Trehalose

The University of California, Irvine (UCI) successfully enrolled the first participant in its newly established Expanded Access Protocol (EAP) program. Under the direction of Namita Goyal, MD, Professor of Neurology, UCI School of Medicine, and Director of UCI Health ALS Services, the EAP program allows people with ALS who do not qualify for trials to access investigational drugs that are not yet approved by the FDA. UCI’s EAP program is made possible by support from the axeALS Foundation in partnership with the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital.

Dr. Merit Cudkowicz is featured in a poignant article from The New Yorker, "When Dying Patients Want Unproven Drugs." The article explores the patient perspective of research and the road to FDA approval.

REDUCING TIME TO DIAGNOSIS

One of our major areas of research is focused on the earliest signs of ALS (biological, digital or/and clinical) to allow for much earlier diagnosis and treatment intervention. The time from symptom onset to diagnosis for an aggressive disease like ALS is unacceptably long, especially since we know that early intervention is more effective. Our Healey & AMG Center researchers are developing tools to reduce the time to diagnosis from nine months to a matter of weeks. Efforts include a potential blood test for ALS – indicating the existence of the disease before symptoms appear – and a wearable device that can detect changes in gait sooner, among others. Most recently, Healey Center teams and our collaborators were awarded three grants from ALS Finding a Cure, the ALS Association, and the Muscular Dystrophy Association.

ALS Finding a Cure® (ALSFAC) and The ALS Association’s ALS Early Diagnostics Grants

ALS Finding a Cure (ALSFAC) has awarded a $400,000 grant to a team of researchers from Massachusetts General Hospital, led by Ghazaleh Sadri-Vakili, MS, PhD, NemDx and the International Centre for Genetic Engineering and Biotechnology for their project “Developing a Comprehensive Blood Test for Sporadic and Familial ALS.” Sadri-Vakili, Director of NeuroEpigenetics Laboratory at the Mass General Institute for Neurodegenerative Diseases and Associate Investigator at the Neurological Clinical Research Institute, serves as Co- Principal Investigator. Read the full article here.

Ghazaleh Sadri-Vakili, PhD, also received a grant for her project which aims to identify specific gene fusions that can be measured in the blood and spinal fluid and may serve as biomarkers of early ALS. The project specifically targets so-called breakpoint gene fusions.

Mark Garret, MD, was awarded an ALS Early Diagnostics grant with Everything ALS for his project which aims to develop a decentralized and open innovation platform that will enable remote assessments of limb activity, speech, cognition, and behavior. 

Muscular Dystrophy Association (MDA) Awards Grant to Team Testing Syde Device from SysNav

A team of investigators from the Healey & AMG Center, including James Berry, MD, MPH, have been awarded an MDA grant to test a wrist and ankle-work sensor called the Syde device from SysNav in people with ALS. The study builds on data from Duchenne Muscular Dystrophy (DMD), showing that gait velocity slows over time. This endpoint has acceptance by the EMA as a primary endpoint in registration drug trials for DMD. The team is working with Drs. Laurent Servais and Margaux Poleur, colleagues in Belgium and the UK, to test the device in people living with ALS.

DATA SHARING IN ALS RESEARCH

Mass General’s ALS team, with the Neurological Clinical Research Institute’s Center of Innovation and Bioinformatics (CIB), has been a leader in the collection, curation, and sharing of data from clinical trials, natural history studies, digital outcome measure studies, and patient samples, sharing this valuable information widely and globally.

Under Alex Sherman’s leadership, the CIB team has introduced innovative breakthrough concepts and products like NeuroBANK^®, a patient-centric research platform and accelerated research environment, used by hundreds of investigators at 80+ clinical sites in 14 countries; PRO-ACT™, a harmonized anonymized dataset from 23 ALS clinical trials that is an invaluable resource for the design of future clinical trials and the identification of unique observations, novel correlations and biomarkers of ALS; and The SigNET^™ (NeuroGUID) Platform for unique and secure patient identification across the research continuum.

PatientsLikeMe ALS contribution expands free PRO-ACT database

Earlier this summer, ALS News Today published a fantastic article about the new PRO-ACT database and the work Alex Sherman & team are doing. The collaboration between the NCRI and PatientsLikeMe (PLM) allows scientists around the world to access the PRO-ACT database, bringing us closer to a cure for ALS.

Mitsubishi Tanabe Pharma America (MTPA) to Partner with ALS/MND Natural History Study Consortium to Collect Real-World Data in ALS with the Goal of Improving Patient Care

MTPA announced a partnership with the ALS/MND Natural History Study Consortium at Mass General to expand ALS research. "We’re honored to collaborate with the Consortium to advance our understanding of this complex disease," they said.

UPDATES FROM THE MULTIDISCIPLINARY CARE CLINIC

New Employee Feature: Jamie Cormier, MS, Genetic Counselor

We are thrilled to welcome Jamie Cormier, our new Genetic Counselor to the team at the Healey & AMG Center. Jamie comes to us with experience from Kean University in New Jersey, where she obtained her Master of Science in Genetic Counseling. She currently serves as a reviewer for the Journal of Genetic Counseling, at which she evaluates papers eligible for publication. We are pleased to welcome Jamie’s expertise and passion for genetic studies and look forward to her contributions to the Healey & AMG Center.

“The first three words that come to my mind when I think about my job are education, advocacy, and compassion,” Jamie says.

With mentoring from Diane Lucente, MS, LCGC, Jamie has started seeing participants (individuals who may have an ALS causative gene) enrolled in the Dominant Inherited ALS Network study (DIALS) for genetic counseling consultations. Her days involve prepping for appointments, which includes reviewing the personal and family history of the participants. Genetic knowledge continues to evolve, so part of her job also includes variant interpretation. There are many resources available to help research genetic changes, what is currently known about the change, and how it could affect an individual/family.

She is very grateful to be someone who hears the intimate details and emotions of individuals and their families. She hopes the information she provides, and the conversations are helpful to them.

The Healey & AMG Center annual Young Investigator awards encourage early-career scientists to pursue ALS research. Thanks to the generosity of our donors, we are able to award three investigators with resources toward investigations that exemplify innovation in ALS. These awardees and fellows are expanding our community of ALS researchers with new ideas and approaches that we know will bring us more quickly to the answers we need. 

We are thrilled to announce the following award recipients: 

2023 Byrne Family and Judith & Pape Adams Fellow

Nandini Ramesh, PhD 

Dr. Ramesh is a third-year postdoctoral research fellow working under the mentorship of Dr. Clotilde Lagier-Tourenne at Mass General and Harvard Medical School. She received her PhD in Human Genetics at the University of Pittsburgh where she worked on developing genetic models in Drosophila to investigate the role of RNA-binding proteins in neuromuscular diseases. Dr. Ramesh is interested in understanding the molecular basis of neurodegenerative disease pathogenesis to aid in developing targeted therapeutic interventions. Her postdoctoral research focuses on TDP-43, a key pathogenic protein in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In patient tissues, TDP-43 is abnormally mislocalized and aggregated in the cytoplasm of affected neurons. The goal of Dr. Ramesh’s project is to apply high-throughput optical-pooled CRISPR screening technology, in collaboration with the laboratory of Dr. Paul Blainey at the Broad Institute, to discover novel genes that directly influence TDP-43 localization and function in human neurons. The genes and downstream pathways identified from the screens will help elucidate the underlying mechanisms of TDP-43 mislocalization and lay the foundation for the development of new therapeutic strategies for ALS/FTD patients.

Corcoran Family Award from the Sean M. Healey & AMG Center for ALS

Mark Garret, MD for the PREVENT ALS/DIALS Study 

The PREVENT ALS / DIALS (Dominantly Inherited ALS Network) study is an observational research study studying >200 individuals at risk for genetic forms of ALS (10-15% of total ALS cases) led by Dr. Garret and Dr. James Berry at Mass General. The study involves genetic testing to determine if individuals carry genetic variants that cause ALS, after which they undergo blood and/or spinal fluid collection, strength testing, cognitive testing and speech recordings at regular intervals over many years to help identify markers of disease prior to onset of ALS symptoms. Dr. Garret proposes to analyze existing data in the DIALS study to determine the psychological impacts of returning genetic testing results to at risk individuals and to compare the sensitivity of different methods of quantitative strength testing to detect early weakness in ALS. This award will also allow continued expansion in the enrollment of DIALS to reach a broader and more diverse group of ALS gene carriers.

We are so grateful to the generosity of the Corcoran family who made this award possible in memory of John M. Corcoran, who was committed to helping those who need it the most.

2023 Wood Family Award: 

Tiziana Petrozziello, PhD for “Deciphering the Role of Tau in ALS”

Tau is a neuronal protein involved in several critical cellular functions, including stabilizing the cytoskeleton of neurons. Tau can undergo different modifications, including phosphorylation (pTau). Accumulation of pTau led to the disruption of its normal function in neurodegenerative disorders, such as Alzheimer’s disease (AD). Given the critical role played by tau in the degeneration of neurons, several tau targeting therapies have been developed and are currently in trials for AD. Similarly, the measurement of tau protein in patient biofluids, such as cerebrospinal fluid (CSF) and plasma, suggest that tau may be a viable biomarker of disease. Alterations in pTau have been linked to both sporadic and familial ALS, and Dr. Petrozziello’s studies have supported and provided additional clarity on the role of tau in ALS. She recently demonstrated that pTau is increased in C9ORF72-ALS post-mortem brain samples. Furthermore, the team demonstrated that increases in CSF tau levels in people living with ALS correlated with a faster disease progression, suggesting that tau could be used as a biomarker in ALS. Currently, Dr. Petrozziello’s studies are focused on better understanding how alterations in pTau contribute to motor neuron loss in C9ORF72-ALS and the role of nuclear tau in ALS. In addition, her studies will determine whether targeting tau and/or molecular pathways altered by pTau could serve as a new therapeutic strategy for the treatment of ALS. Lastly, the team has successfully measured plasma tau and is currently focused on determining whether plasma tau could serve as a biomarker for ALS and thereby hasten diagnosis of disease and/or predict disease progression. 

We are excited to partner with the Wood family to attract young scientists to the field of ALS and train the next generation of talented scientists. 

COMMUNITY EVENTS

We are so grateful for our ALS community, which brings people together to celebrate and fundraise for our important work. Thank you for your participation at any level.

The Bourque Family Foundation Captains Ball 2023 took place on Thursday, September 21, 2023 at Big Night Live. More information is available here.

The Cabell Fooshe Golf Tournament was held on September 25, 2023. Keller Williams and the McLean/Great Falls office hosted a golf tournament at the Westwood Country Club in Vienna, VA. Part of the proceeds will be donated to the Healey & AMG Center in memory of Healey & AMG Center patients, Beth Albright and Tyler Suiters.

Two Thumbs Up Initiative: Yossi Nasser and fellow supporters of the Healey & AMG Center for ALS are planning to summit Mt. Kilimanjaro on October 18.

As he saw his mother lose her mobility throughout her battle with ALS, Yossi decided to never take his own for granted, and more than that, it would be meaningful to achieve a physical challenge in her honor. In fact, during her last few months, when Yossi told his mother about the idea of climbing the 7 peaks of each continent in the world, to raise awareness and funds to advance research for individuals with ALS, she gave him two thumbs up, which was the only way she was able to communicate at that time. Hence, Yossi dubbed the 7-peak challenge, as Ariella's "two thumbs up". Mt. Kilimanjaro will be climbed in late October as the first of the seven peaks. 

If you are interested in more information on the Two Thumbs Up Initiative and supporting Yossi’s climb of Mt. Kilimanjaro, please click here.  

The Pete Frates 5K will be held on Sunday, November 5, 2023 10 a.m. at Lynch Park, in Beverly. Learn more/ register here. This year, proceeds will benefit the ALS House Call Program.

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