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

We have reached a critical turning point in our quest to develop effective treatments for ALS. As we move closer to understanding what triggers the disease, we are making great progress with slowing disease progression with FDA approval of two new therapies over the last year and promising results from our HEALEY ALS Platform Trial. We are also focused on increasing access through our national network of Expanded Access Protocol (EAP) sites to reduce barriers to access and allow more individuals with ALS to participate in our evaluation of investigational compounds, bringing us more quickly to the answers we need.

We are excited to share that the Healey & AMG Center received several new National Institute of Health grants this year to greatly expand our national PREVENT ALS, biomarker and personalized medicine research approaches. We are eager to expand our efforts to identify biomarkers for early diagnosis and treatment response.

Your support is critical to our success and we rely on your continued partnership to bring us to the finish line we are confident is within reach. Our goal is to continue to provide 24/7 care to our patients and also ensure we sustain our ground-breaking work and make the discoveries that will make ALS a disease of the past.

We are extremely encouraged by the progress our basic scientists are making in strategies and treatments that will allow for repair and regeneration. Our fundraising goals are ambitious but reflect our determination to keep our momentum going to move closer to our goals: stop, repair, and prevent ALS.

We look forward with you to a year of new breakthroughs and new treatments for people living with ALS.

Warmly,

Merit Cudkowicz, MD, MSC

EAPs: Extending Experimental Therapy Access

The Healey & AMG Center for ALS continues to be a leader not only in developing effective treatments for ALS but also ensuring that as many people with ALS (PALS) as possible have access to experimental drugs. We do so through our Expanded Access Protocol (EAP) programs, which give those who are not eligible for clinical trials across the country access to experimental drugs not yet approved by the FDA. 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.

Read our EAP Newsletter

Your support of this innovative approach to accelerating the testing of promising compounds is making outstanding progress, with two of the first four compounds tested moving forward to Phase 3 trials thanks to positive results; three more compounds are currently being tested and two more are in development. We continue to fundraise to allow us to test products in the pipeline and keep testing until we find the cures.

Opening Doors for Scientists

Attracting the world’s brightest and most inquisitive scientists to devote their investigative skills to ALS requires resources, mentoring and opportunities to collaborate with experts in basic research and clinical trial design. We are enormously proud of the scholars who have worked with us already and look forward to the achievements that will emerge from this year’s cohort. Philanthropy makes it possible to offer these opportunities. Thank you.

To learn more about the ALS Scholars in Therapeutics program at the Healey & AMG Center, click here.

Support for ALS Nursing

The work that we do here at the Healey & AMG Center would not be possible without our amazing team of nurses. Their dedication to our patients, advocacy for better and safer clinical practice, and, most importantly, their expertise in our divisions exemplifies the standards of care at Mass General. Philanthropic support is vital to improving access to registered nurses (RNs) and funding nursing services that unfortunately are not covered by medical insurance. We are grateful to the donors to the Healey & AMG Center for their belief in us. Your partnership is essential to our success.

THE YEAR AHEAD

Biomarkers for Early Diagnosis and Treatment Response

The HEALEY ALS Platform Trial has exceeded all our expectations, allowing us not only to quickly determine the effectiveness of promising investigational compounds, but also to collect important information around biomarkers we can use to measure the presence of ALS. Identifying more biomarkers that reflect the variability of this disease will allow us to identify more therapeutic targets, and then rapidly screen and test potential therapies that reverse and repair damage and ultimately prevent ALS from occurring in the first place.

The HEALEY ALS Platform Trial serves as an efficient and effective tool to accomplish this goal. The first four compounds tested in the Platform Trial leveraged biomarkers that included a speech app, home spirometry (a breathing test that can be done at home) and neurofilaments (which indicate axonal damage), all valuable measurements of disease progression. While encouraging, we need more, and more precise, biomarkers that can detect and predict clinical effect sooner. We would now like to build out the biomarker component of the HEALEY Platform Trial by adding iPSC lines (induced pluripotent stem cells) to all regimens to see if we can predict responders; ensure all participants have their neurofilament and other fluid biomarkers measured; analyze genomics; and employ digital apps to assess gait, mobility and function in the home. Embedding these biomarkers into the existing HEALEY Platform Trial piggybacks on the already successful protocols we have in place. We need philanthropic support to add these biomarkers to the next two regimens scheduled to be tested in the platform.

Repair and Regeneration

To individuals living with ALS, any return of function can significantly improve their quality of life. Researchers at the Healey & AMG Center are identifying the specific biological pathways in cells involved in muscle and nerve function that are lost during the development of ALS and working on strategies to repair them. Damaged nerves are common in many diseases and disorders of the brain and spinal cord system, and repairing these neuron functions and connections will help individuals with ALS as well as many other conditions. Cross-disciplinary research like this often does not fit within the governmental and foundation grant parameters and we are grateful for our partnerships with our supporters who help to further this important research.We are so grateful for the opportunity to raise awareness and funds for this exciting research. A few examples of our work on repair and regeneration are described here:

Using Stem Cells to Repair Neurons Damaged by ALS -

Brian Wainger, MD, PhD

Dr. Wainger is collaborating with members of our neurosurgery team to develop a novel therapy to improve neurosurgical outcomes after nerve or spinal cord injury. Building on the nerve transfer surgeries performed at Mass General – replacing a damaged nerve with a healthy nerve from a nearby muscle to restore strength – our research teams are pioneering a novel approach to nerve transplants using motor neurons derived in the laboratory from non-embryonic, human stem cells. Such motor neurons have already shown promise in animal experiments where they were injected near the muscle, grew, made connections to the muscle and maintained muscle health. The muscles did not undergo irreversible damage, setting the stage for a successful nerve transplant. Because muscle degeneration is implicated in ALS, there may be additional benefits of the stem cell derived motor neurons in ALS as well as other spinal cord injuries that need repair.

This work to return function for individuals who have spinal cord injury is at the cutting-edge of both neurosurgery and basic science. Dr. Wainger’s commitment to adapting and expanding this research to apply to individuals with ALS is exciting and innovative and outside the boundaries of traditional funding mechanisms. Philanthropic support for this work is critical to move this into patients.

Restoring the Stathmin -2 (STMN2) Protein to Restore Function – Clotilde Lagier-Tourenne, MD, PhD

The discovery that loss of the protein TDP-43 from the cell nucleus occurs in 98% of people with ALS – both sporadic and inherited – has recently led to insights about the gene and related protein most affected by that loss: Stathmin-2 (STMN2). STMN2 is critical to the repair of motor neurons and the formation of healthy neuromuscular junctions -- points of contact between neurons and muscle cells where they communicate with each other. In people with ALS, STMN2 protein levels are dramatically reduced leading to disconnection of the motor nerve from muscles. Failure of muscle function is a primary symptom of ALS, and so identifying molecules that can allow surviving motor neurons to regenerate and reconnect with the muscles will be an extraordinary breakthrough.

Promising Gene Therapy: Dr. Lagier-Tourenne and her colleagues demonstrated that increasing the levels of STMN2 can restore the ability of neurons to grow axons after injury. In collaboration with Ionis Pharmaceuticals, Dr. Lagier-Tourenne and her team developed a gene therapy – antisense oligonucleotides (ASOs: an approach successfully developed to treat several neurological diseases, including a familial form of ALS) – that blocks the abnormal splicing of STMN2 in cultured motor neurons. Dr. Lagier-Tourenne’s team now needs to test this gene therapy in animal models to ensure it is safe and effective before moving into patients.

Statins and other chemical compounds: Dr. Lagier-Tourenne and her collaborators are also searching for chemical compounds that may increase the levels of STMN2. Her team’s initial screen identified statins (medication widely used to lower cholesterol in individuals with heart disease) as potent inducers of STMN2. The challenge for Dr. Lagier-Tourenne’s team now is to understand how neuronal axons respond to statins. Researchers have observed that statins promote the growth of axons in cultured neurons, but their impact needs to be tested in animal models before moving into clinical trials in humans. Dr. Lagier-Tourenne received initial support from ALS Finding a Cure and Mass General Brigham Innovation for her work investigating statins and developing novel compounds similar to statins but designed for neurological diseases with the ability to get into the brain and spinal cord.

Statins are only one potential therapeutic option that needs to be investigated. The screening also revealed other small molecules that can increase STMN2 levels by targeting other steps along the pathway. Support will help us learn more about the mechanics behind the molecules that increase STMN2 levels and allow neurons to regenerate. With your commitment, we will screen more candidates quickly, revealing the therapy with the most potential to help, and refer into clinical trials that can make a meaningful difference to our patients.

rivALS Teaming Up to Raise Funds for ALS

The Healey & AMG Center is proud to partner with former NFL player, Tim Green and his family on raising funds to accelerate research as we continue advancing towards the cures, through the Tackle ALS fundraising campaign. Rival franchises, the Atlanta Falcons and New Orleans Saints are teaming up to host two special “rivALS” games in both of their NFL matchups this season. There will be a 50/50 raffle at each game, with partial proceeds benefitting the Tackle ALS campaign.

Read more here, and tune in to the first game on November 26!

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/.