ALS oral therapy
ALS oral therapy slows disease progression in preclinical testing
M102, an oral therapy for ALS, slowed disease progression in preclinical tests. It protects nerve cells by activating NRF2 and HSF1 pathways. The therapy improved muscle function and body weight in mouse models.
M102, an experimental oral therapy designed to simultaneously activate two molecular pathways that protect against nerve cell damage, showed promise in preclinical models of amyotrophic lateral sclerosis (ALS), according to a study.
The compound, discovered and developed by researchers at the University of Sheffield’s Institute for Translational Neuroscience (SITraN) in the U.K., significantly slowed disease progression and preserved muscle function in mouse models of the disease, as well as protected nerve cells from damage in lab experiments.
“The preclinical studies not only showed improvement in movement, gait, and nerve function in mouse models, but it also protected motor neurons grown in the laboratory from damage,” Pamela Shaw, co-author of the study and director of SITraN, said in a university news story.
The study, “M102 activates both NRF2 and HSF1 transcription factor pathways and is neuroprotective in cell and animal models of amyotrophic lateral sclerosis,” was published in Molecular Neurodegeneration.
M102 designed to simultaneously activate two molecular pathways ALS, also called motor neuron disease or MND, is marked by the progressive degeneration and death of motor neurons, the specialized nerve cells that control movement.
The disease’s underlying causes aren’t fully understood, but a few molecular factors have been shown to play key roles. These include oxidative stress — a form of cell damage caused by highly reactive molecules that contain oxygen — as well as the misfolding and clumping up of certain proteins.
M102 is an oral small molecule designed to simultaneously activate two molecular pathways, called NRF2 and HSF1. The NRF2 pathway activates antioxidant mechanisms that help cells mitigate oxidative stress, while the HSF1 pathway plays key roles in stabilizing proteins to prevent abnormal folding and clumping.
“MND is one of the cruellest diseases, robbing people of their mobility and independence often at an alarming speed. We are now at a point where scientific understanding is finally catching up,” Shaw said. “Our discovery of M102 gives real hope that we can substantially slow the progression of this disease.”
The experimental therapy is currently being developed by Aclipse Therapeutics, which has received millions of dollars in grants to advance the therapy into clinical trials. Aclipse has been running preclinical tests to support an Investigational New Drug application, which is a formal request to U.S. authorities for permission to begin clinical testing in people. Aclipse is now planning to advance the therapy into clinical trials pending additional funding.
