TQS-168, an investigational therapy being developed by Tranquis Therapeutics, reduced inflammation in mouse and human models of amyotrophic lateral sclerosis (ALS), and prolonged survival in the mice, according to a preclinical study.
Based on these findings, Tranquis is moving the therapy into Phase 1 clinical studies.
“We believe TQS-168 represents a new class of treatment for ALS patients and these data paint a compelling picture which shows, in this preclinical model, a potential advance over approved treatments,” Jonas Hannestad, MD, PhD, chief medical officer and head of R&D at Tranquis, said in a press release.
“We are rapidly advancing TQS-168 into Phase 1 clinical studies to assess safety, pharmacokinetics, and pharmacodynamics,” Hannestad added. Pharmacokinetics is the movement of a drug into, through, and out of the body, while pharmacodynamics refers to the effects of a drug on the body.
A poster with the findings, titled “The small molecule myeloid cell modulator TQS-168 normalizes the inflammatory phenotype of immune cells from ALS patients and extends survival in the SOD1-G93A ALS mouse model,” was presented by Hope Lancero, PhD, a scientist at Tranquis, during the Neuroscience 2021 annual meeting.
Neuroscience 2021, held virtually this year from Nov. 8–11, is the annual meeting of the Society for Neuroscience.
Although the exact cause of ALS is largely unknown, inflammation is believed to play a key role.
Myeloid cells — blood cells such as monocytes and macrophages — normally rush into threatened areas of the body to provide a first line of defense against a possible attack. However, in ALS and other neurodegenerative conditions, these cells can become overly active and release a range of molecules that are damaging to nerve cells.
In ALS, pro-inflammatory monocytes are hallmarks of disease progression.
TQS-168 was designed to reduce myeloid cell activation and reprogram them to restore their normal function. According to the company’s website, TQS-168 was shown to be able to do exactly this in cells grown in the lab.
Now, scientists at Tranquis looked at the effects of TQS-168 in a mouse model of ALS carrying a mutation in the SOD1 gene. SOD1-G93A mice develop symptoms similar to those of human ALS as early as within a few weeks of age.
The scientists gave the mice TQS-168 at 50 milligrams per kilogram of body weight, three times per week, and examined changes in markers of inflammation. They found that TQS-168 decreased the levels of both inflammatory monocytes and inflammation-promoting signaling molecules.
Moreover, mice treated with TQS-168 lived six days longer than those left untreated (135 vs. 129 days).
To examine whether these changes also could hold true in humans, the scientists took blood from patients with ALS and mixed the samples with various amounts of TQS-168 for four hours. TQS-168 reduced the percentage of inflammatory monocytes, which are usually increased in patients with ALS, as compared with healthy controls.
“These data provide convincing evidence that validates our unique approach of developing first-in-class therapeutics that target immune mediated CNS [central nervous system] and non-CNS indications by reprogramming dysfunctional myeloid cells, and that our lead program has the potential to become a disease-modifying therapy that would benefit ALS patients,” said Hannestad.