Health
QurAlis is preparing for clinical development of its therapeutic candidate QRL-101
(Business Wire) –Qur Alis Corporation, a biotechnology company that develops breakthrough precision medicines for ALS and other genetically validated neurodegenerative diseases, today Cell report Of the title Human Amyotrophic Lateral Sclerosis Excitatory Phenotypic Screening: Target Discovery and Verification QurAlis founders Kasper Roet, Ph.D., Clifford Woolf, MD, Ph.D., Kevin Eggan, Ph.D. Developed. Combined with the compound library generated by Pfizer, it identifies drug targets for the treatment of hyperexcitatory neurodegeneration in ALS patients.
This publication describes a live cell screening strategy that targets abnormal electrophysiological properties to uncover targets that regulate the intrinsic hyperexcitatory activity of ALS motor neurons. In this unbiased screen using human ALS motor neurons, Kv7.2 / 7.3 was identified as a highly over-displayed drug target.
Kv7.2 / 7.3 dysfunction in ALS motor neurons was previously identified by the doctor. Kevin Eggan, Clifford Woolf, Brian Wainger, and Evangelos Kiskinis led to the development of a precision medicine program at QurAlis to develop a selective Kv7.2 / 7.3 ion channel opener for treating ALS patients.
The effectiveness of Kv7.2 / 7.3 as a drug target in ALS patients is also strongly supported by the results of clinical trials recently published at JAMA Neuro, where Kv7 regulation reduces the excitability of spinal and cortical motor neurons. Was shown. Patient survival.
Through the deconvolution of bioinformatics, the screen, which was a collaborative effort of scientists at Boston Children’s Hospital, was co-lead author Dr. Xuan Huang, Harvard Stem Cell Research Institute, Physer Center for Therapeutic Innovation, and AMPA and D2 dopamine receptors. I found. As a new excitatory regulatory target that contributes to the excitatory activity of ALS motor neurons.
These findings suggest that QurAlis’ selective Kv7.2 / 7.3 opener, QRL-101 (QRA-244), may be an effective treatment for patients suffering from motor neuron degeneration caused by hyperexcitability. Strengthens our hypothesis that there is.Previous studies have identified Kv7.2 / 7.3 as a drug target for ALS, and the impartial nature of this screening further emphasizes the importance of Kv7.2 / 7.3 in ALS motor neuron dysfunction. Masu“
Dr. Kasper Roet, CEO and Founder of QurAlis
“It is widely believed that suppressing motor neuron hyperexcitability in ALS patients can slow the progression of the disease,” said Leonard van den Berg, MD, chairman of the European Network for Curing ALS. “This study is a new and powerful method for phenotypic screening of excitement using patient-derived motor neurons to identify drug targets that act on abnormal excitability, and is more effective with fewer side effects. It shows that it offers the potential to create new treatments. “
Source:
Journal reference:
Yellow, X., Et al.(2021) Excitatory phenotypic screening for human amyotrophic lateral sclerosis: Target discovery and validation. Cell report.. doi.org/10.1016/j.celrep.2021.109224..
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