Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons begin to deteriorate, preventing voluntary muscle movements. Without this innervation the muscles begin to atrophy, and the average person ultimately dies around 39 months after diagnosis. A recent study identified a new genetic pathway to target in conjunction with medication, which reduced neurodegeneration and extended life span in an animal model. The research was led by Kevin Eggan of Harvard University and the paper was published in Science Translational Medicine.
ALS, or Lou Gehrig’s disease as it is sometimes known, is the most common motor neuron disease and affects about 2 in every 100,000 people, including world renowned physicist Stephen Hawking. Current treatment options focus on palliative care and managing symptoms, including medications to soothe spastic muscle movements and exercises to maintain breathing.
Eggan and his team discovered about 7 years ago that motor neuron degeneration is connected to glial cells; non-neuronal cells that support the nervous system. They were later able to implicate prostanoid molecules, which facilitate inflammatory and anaphylactic responses, as the mechanism affecting glial cells that have mutated receptors. This current research revealed that inhibiting the receptors in these cells was actually able to slow damage to the motor neurons.
As a result of this method, the extended survival time by 5-10 percent in animal models. Applying that to the 39 month survival rate in humans, this could mean an extra 2-4 months of life. Though this might not sound like much and is still far away from a cure, it’s a promising start for developing a new treatment.
“[A]ny ALS patient would be excited about this extended life span,” Eggan said in a press release.
Prior to this study, Eggan had completed in vitro testing of this target on motor neuron cells grown from human stem cells. Having successful testing in an animal model in the current study was incredibly important, as it is the first indication that it can work at the systemic level and could possibly be adapted into a functional treatment. Additionally, the fact that the two experiments had nearly identical results could mean that more research can take place in a dish, reducing the amount of animals that need to be used as the treatment is developed.
“This is a very exciting period for those whose lives are threatened by ALS, and it is exciting for my lab,” Eggan said. “First, we recently identified a pathway that we think is important for degeneration inside the motor neuron, and now we’ve found this pathway in cells outside the motor neuron. This has potential to have a very substantial effect on what’s happening in ALS.”
Eggan’s lab is also nearing the first phase human trials of the effects on ALS with a drug that was developed to treat epilepsy. Though the drug has already gone through FDA approval, this off label use will also need to be tested for safety and efficacy before being used in a clinical setting.