Begun in 2017, the Project ALS Pre-Clinical Core (the Core) is the first rational, aggressive effort to rapidly and thoroughly test promising therapies for safety and potential efficacy in ALS before they reach human clinical trial.
Located at the Columbia University Motor Neuron Center in New York, in partnership with leading research universities and drug companies, the facility utilizes the most predictive laboratory models of ALS disease to fast-track the best drug candidates to human trial. Directed by Drs. Serge Przeborski, Hynek Wichterle, and Neil Shneider, the Core subjects drug candidates to a rigorous battery of testing to measure for such outcomes as dosing and delivery methods, brain penetrance, and, ultimately, target engagement and efficacy.
In its first year, the Core tested four potential ALS therapies: (1) An FDA approved drug called sunitinib, originally developed for the treatment of cancer (2) AMYLYX, a drug already being tested in ALS patients (3) alsterpaullone, a powerful molecule that may be neuroprotective (4) PB Compound, a novel drug developed by Core scientists that shows early signs of promise. This year the Core is testing eight additional drug candidates.
The Core is the culmination of 20 years of Project ALS research achievements in genetics, stem cell research, and basic research studies. These breakthroughs allow the Core to target ALS more accurately.
Recent discoveries in ALS genetics provide new therapeutic targets for the Core and beyond. For example, when Project ALS incorporated in 1998, only two genes had been identified as contributors to ALS disease. Now there are well over 50 ALS genes in play. Breakthroughs in genetics have also generated helpful new laboratory models of the disease. Project ALS piloted many of the first experiments to “turn off” gene mutations in ALS.
Additionally, the identification of new “constellations” or combinations of ALS genes across thousands of ALS patients has given researchers major clues about why the brain goes wrong in ALS, and exactly where to intervene therapeutically. For example, genetics findings led Project ALS research scientists to focus recently on the autophagy pathway—a new target in ALS treatment. Several drug candidates—including autophagy modulators–are now being tested in the Core.
It is highly unlikely that a cure for ALS disease will come until we understand more about brain development, motor behavior and circuitry. Project ALS remains committed to supporting select basic research, as much of its 20 years of progress has resulted from the observations in this field. In fact, basic research has inspired many recent approaches to ALS therapies, including gene therapy, small molecule screenings, and stem cell approaches.
Project ALS enables communication between basic researchers and doctors. For example, a basic study in motor neuron biology in 2001, resulted in the generation of patient-specific motor neurons, a technique named Scientific Breakthrough of the Year by Time magazine in 2009. Doctors now routinely use a tool known as “ALS in a Dish”—a small model of an individual patient’s ALS—to screen for drugs.
Project ALS nurtures a network of scientists from academic centers including Columbia University, Harvard University, Boston Children’s Hospital, New York University, Massachusetts General Hospital, Johns Hopkins, The Salk Institute, Memorial Sloan Kettering Cancer Center, among others, that feed each other’s ideas and observations—and the Core. The Project ALS network shares one goal—to deliver drugs to human trial that will slow and/or stop ALS.