The publication describes a live-cell screening strategy targeting abnormal electrophysiological properties to reveal targets that modulate the intrinsic hyperexcitability of ALS motor neurons. This unbiased screen using human ALS motor neurons identified Kv7.2/7.3 as a strongly overrepresented drug target.
Dysfunction of Kv7.2/7.3 in ALS motor neurons had been previously identified, which led to the development of a precision medicine program at QurAlis to develop a selective Kv7.2/7.3 ion channel opener to treat ALS patients.
The validity of Kv7.2/7.3 as a drug target for ALS patients was recently also strongly supported by results of a clinical study published in JAMA Neuro showing that Kv7 modulation can decrease spinal and cortical motor neuron excitability, both of which have been linked to patient survival. They also found AMPA receptors and D2 dopamine receptors as novel excitability modulating targets that contribute to ALS motor neuron excitability.
"These research results strengthen our hypothesis that the QurAlis selective Kv7.2/7.3 opener, QRL-101 (QRA-244), has the potential to be an effective therapy for patients suffering from hyperexcitability induced motor neuron degeneration," said the CEO and Founder of QurAlis. "Previous research has identified Kv7.2/7.3 as an ALS drug target and the unbiased nature of this screen further emphasizes the importance of Kv7.2/7.3 in ALS motor neuron dysfunction."
Role of ion channel, Kv7.2/7.3 in ALS
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