2024 WINTER NEWS
THANK YOU FOR PUSHING OUR RESEARCH FORWARD
In 2024, the Project ALS Therapeutics Core, the Core, achieved outstanding progress in three critical areas: Models, Motor Neuron Rejuvenation, and Medicine.
Our goal for 2025? To fulfill the promise of these three “Ms” by advancing transformative therapies and analytic tools to ALS clinical trials.
Let’s keep moving forward—together.
With Gratitude,
Team Project ALS
SUPER MODELS EMERGE
In 2008, Project ALS, with its partners at the Jenifer Estess Lab for Stem Cell Research, Columbia, and Harvard, pioneered the world’s first laboratory models of human ALS. Known as “ALS in a Dish” or iPS/ALS modeling, this discovery platform has continuously evolved, becoming a more reliable predictor of preclinical drug efficacy.
Recognizing that no two cases of ALS are the same, the Core is now leveraging cutting-edge AI technologies to enhance these models. By integrating a suite of AI technologies with disease model systems, the Core has begun to identify discrete differences among ALS patients—a critical step toward developing personalized therapies.
AI is also driving model systems in the Core to pinpoint the earliest signs of ALS-related motor changes in people, setting the stage for earlier interventions and more effective treatments.
Learn more about “ALS in a Dish” here, and read TIME Magazine’s 2008 Medical Breakthrough on the subject here.
Motor Neuron Rejuvenation
Can we reverse the effects of aging? It might sound like science fiction, but this year, the Core uncovered promising evidence suggesting that we can restore a youthful state to adult motor neurons—the very brain cells targeted by ALS. Remarkably, when Core scientists reintroduced two transcription factors active during normal brain development, motor neurons in mice with ALS become disease resistant.
While it’s still early days, 2025 will reveal whether this approach can work not only in mice, but in people living with ALS. Learn more about this research innovation here.
Advancing Medicine
One of the reasons ALS clinical trials have a 99% failure rate is that many therapies that reach trial have not undergone thorough pre-clinical testing. That’s the mission at the Core: to conduct rational, rigorous, and aggressive testing of promising drugs and therapies long before they reach clinical trial.
Project ALS is proud to report that prosetin, the first new drug designed at the Core for the treatment of all forms of ALS, is now entering clinical trial for people living with ALS.
Looking ahead to 2025, the plan is to prepare additional therapies for trial. Among the most promising candidates are the “paullones.” Medicinal chemists at the Core have recently developed the fifth generation of kleinerpaullone, which is proving to be orally available, brain-penetrant, and neuroprotective. Learn more about the story of the paullones here.
Other exciting drugs under development for 2025 include protease inhibitors and ferrostatins. In ALS, proteases damage essential proteins and accelerate disease progression. By inhibiting these enzymes, protease inhibitors offer potential protection for cells, slowing disease progression. Ferrostatins, another class of compounds, block ferroptosis, a form of cell death first identified by Core researcher Dr. Brent Stockwell. By preventing ferroptosis, ferrostatins may help protect neurons from damage and degeneration.
