Reducing toxic protein aggregates…potentially effective in a wide range of patients
[의약뉴스] AI Therapeutics, a US biopharmaceutical company, obtained positive results in a phase 2a clinical trial of a treatment for amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) with a novel mechanism.
AI Therapeutics announced on the 5th (local time) the results of a phase 2a clinical trial of AIT-101 (LAM-002A), which was conducted on 15 patients with amyotrophic lateral sclerosis with C9ORF72 mutation.
In the clinical trial, participants who received AIT-101 showed increased expression of the target binding biomarker (sGPNMB) and a 73% reduction in the toxic protein aggregate poly (GP) over 12 weeks.
In addition, the primary endpoints for safety, tolerability, and confirmation of brain delivery of the drug and its three active metabolites were satisfied.
AI Therapeutics’ AIT-101 is the first in its class of potent, highly selective lipid kinase PIKfyve inhibitors. Inhibition of PIKfyve induces activation of the transcription factor TFEB, thereby increasing clearance of toxic protein aggregates through the autophagic lysosomal pathway.
“The positive results of this clinical trial are encouraging for the development of AIT-101 for ALS,” said Suma Babu, an assistant professor of neurology at Harvard Medical School and lead investigator of the trial. “AIT-101 is a toxic protein in motor neurons that is a hallmark of ALS. It is a new class of therapeutic candidate that directly targets the removal of aggregates.”
“These data could have broad implications for all ALS patients, not just the C9ORF72 ASL patients tested in this trial. Using a placebo exposure period and an overall short trial period, we were able to efficiently provide information on the biologic efficacy and CNS drug delivery of AIT-101 in C9ORF72 ALS patients and provide a long-term, extended approach to AIT-101 to clinical trial completers. provided,” he said.
AI Therapeutics CEO Brigitte Roberts said, “AI Therapeutics recognizes the urgent need for new therapies that change the course of the disease for underserved patient populations like ALS. We are encouraged by the early findings of AIT-101, a first-in-class PIKfyve kinase inhibitor. We were particularly impressed with the rate and magnitude of the reduction of toxic protein aggregates as measured by poly(GP).”
AI Therapeutics announced that it had demonstrated the efficacy of AIT-101 in the TDP-43 animal model of ALS at the same time as the announcement of the phase 2a clinical data. These new data, together with demonstrated activity in in vitro experiments on motor neurons derived from patients with familial and sporadic ALS, indicate that AIT-101 has the potential for widespread use in multiple forms of ALS.
AI Therapeutics plans to submit detailed results of the phase 2a trial and TDP-43 animal model to a peer-reviewed journal and present them at an upcoming conference.
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