Oral Huntington’s treatment aims to slow disease progression
Loqus23 advances LQT-23 as candidate for development
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Loqus23 Therapeutics said it is advancing LQT-23 for development as a first-in-class oral treatment for Huntington’s disease.
The company said LQT-23 has the potential to slow or halt the onset and progression of the disease, and it plans to submit applications seeking permission to bring the experimental therapy into clinical testing this year.
“The nomination of LQT-23 as our development candidate is a significant moment for LoQus23 and reaffirms our strategy of advancing our pipeline of MSH3/MutS [beta] inhibitors to transform the lives of patients,” David Reynolds, PhD, CEO of Loqus23, said in a company press release.
Huntington’s disease is caused by a triplet repeat expansion mutation in the HTT gene. In this type of mutation, three nucleotides (the building blocks of DNA) — a cytosine (C), an adenine (A), and a guanine (G) — are repeated an excessive number of times.
People with Huntington’s are born with an abnormally long number of CAG repeats, but emerging data suggests it isn’t actually the number of repeats at birth that’s the problem. Studies have shown that, in the nerve cells most affected by Huntington’s disease, DNA repair proteins become abnormally active, allowing the repeat to extend longer, and it’s this excessive extension that ultimately drives the disease.
Blocking protein activity
LQT-23 aims to prevent this abnormal genetic expansion by blocking the activity of the protein MSH3, which is part of a DNA repair complex called MutS-beta.
This complex has been shown to play a key role in driving the abnormal expansion of CAG repeats in Huntington’s, but scientists have found it challenging to target with small molecule therapies, according to Loqus23.
The company has developed and tested multiple small molecule inhibitors of the MutS-beta complex, ultimately zeroing in on LQT-23 as the most promising for clinical use.
“MSH3/MutS [beta] is the most promising and best validated target for [Huntington’s disease], but has been difficult to drug,” said Cyrus Mozayeni, the company’s chair.
The approach employs a distinct mechanism of action, and preclinical studies have demonstrated that LQT-23 can potently and selectively inhibit the MSH3 protein and the MutS-beta complex. It also robustly blocked the abnormal expansion of CAG repeats in cell and animal models of Huntington’s.
“The team has made exceptional progress since the financing in 2024, and the nomination of LQT-23 as our lead development candidate underscores our deep domain expertise, while positioning LoQus23 at the forefront of emerging therapies for the treatment of [Huntington’s disease],” Mozayeni said.
