BALTIMORE — Johns Hopkins researchers believe they've uncovered a potential window in treating ALS.
Amyotrophic Lateral Sclerosis also known as Lou Gehrig's Disease is a debilitating neurodegenerative disorder that affects as many as 30,000 people in the United States, with 5,000 new cases diagnosed each year.
It weakens muscles and slowly limits the body's ability to physically function, ultimately leading to death.
Although there is not a single known cause or cure for the disease, Johns Hopkins Medicine researchers believe targeting astrocytes — a sub-type of cells in the central nervous system — could help treat it.
They believe astrocytes kill off motor neurons, which are cells in the brain and spinal cord that allow people to move, speak, swallow and breathe.
“We think this is particularly important because the astrocyte dysfunction is active after symptom onset in patients with ALS,” says Doctor Nicholas Maragakis, professor of neurology at the Johns Hopkins University School of Medicine and medical director of the Johns Hopkins ALS clinical trials unit. “This finding may enable us to target abnormalities in astrocytes for ALS treatment.”
In their study, researchers analyzed brain and spinal cord tissues from ALS patients that showed a particular astrocyte protein, connexin 43, sending toxic factors to the motor neurons. These abnormalities were particularly active in ALS patients with a family history of the disease, who contracted it in sporadic fashion.
The team also developed stem cell lines from those patients into astrocytes, and found that they induced motor neuron death through hemichannels (proteins that provide pathways for the movement of molecules among cells).
“This is a new pathway that we have shown to be present in ALS tissues, animal models and patient-derived stem cells,” Maragakis says. “It’s also exciting that this particular hemichannel protein seems to be elevated in spinal fluid from patients with ALS and could serve as an important biomarker. This is a true precision medicine approach toward the disease.”
Maragakis Tonabersat, a migraine and epilepsy drug, could potentially block these hemichannels.
Next, researchers will try to establish why the hemichannel is so active in ALS astrocytes, in hopes of better understanding of how the disease progresses.