MDA 2025: Potassium channel could be SMA treatment target
Activating protein improved motor function in SMA mice, scientists say
Activating a protein called potassium channel Kv2.1 may help improve motor function in spinal muscular atrophy (SMA), according to data from experiments done in mice that point to the protein’s potential as a target in SMA treatment.
The findings were presented at the Muscular Dystrophy Association‘s 2025 MDA Clinical & Scientific Conference, held March 16-19, in the talk, “Restoration of motor neuron function via pharmacological in vivo regulation of a potassium channel in SMA mice.”
Motor neurons are the specialized nerve cells responsible for controlling voluntary muscle movements. In SMA, genetic mutations cause motor neurons to get sick and die, which ultimately drives disease symptoms.
Normally, motor neurons communicate closely with proprioceptive neurons, the neurons that sense where the body is in three-dimensional physical space. In a typically developing person, the communication between motor neurons and proprioceptive neurons is crucial for helping maintain balance, regulating tiny adjustments in stance and posture that keep the body upright. But in SMA, these interactions are disrupted as motor neurons degenerate.
That communication between proprioceptive neurons and motor neurons is modulated in part by the motor neuron protein called potassium channel Kv2.1. Data from mouse studies have suggested that, in SMA, motor neurons have reduced expression of this protein.
Kv2.1 activity and SMA treatment
The researchers tested the effects of boosting Kv2.1 activity in a mouse model of SMA, treating the mice with drugs that modulate enzymes known to regulate Kv2.1.
Results showed that treated SMA mice had significant improvements in the reflexes that normally help maintain balance and keep the body upright. They were better able to flip from their backs to stand on their paws. Treated SMA mice also lived slightly longer than their untreated counterparts.
Analyses of the mice’s nerves indicated that the Kv2.1-boosting treatment led to more healthy connections between motor neurons and proprioceptive neurons, suggesting healthier nerve circuits. The treatment also led to more healthy neuromuscular junctions — the connections between motor neurons and muscle cells — and treated mice’s muscles showed more powerful muscle action potential, the electrical flux that triggers muscle contractions. Kv2.1 levels also were increased in motor neurons treated with the enzyme inhibitors roscovitine and calyculin.
The treatment did not prevent motor neurons from getting sick and dying.
“Our study reveals that pharmacological modulation of the potassium channel Kv2.1 restores physiological function of the vulnerable motor neurons as well as the neuromuscular junctions in the SMA … mouse model, providing significant benefits at the behavioral, neuronal and peripheral circuit level,” the researchers wrote in their abstract.
Note: The SMA News Today team is providing live coverage of the 2025 MDA Clinical & Scientific Conference March 16-19 in Dallas. Go here to see the latest stories from the conference.
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