AI Article Synopsis
- Pyroglutamate-amyloid-β (pE-Aβ) peptides are linked to the development of Alzheimer's disease, and PQ912 is a drug that inhibits the enzyme responsible for their formation.
- A clinical trial tested PQ912's safety and effectiveness in both younger and older healthy subjects, finding it well tolerated and showing that drug exposure increased with higher doses.
- Results indicate that PQ912 could significantly inhibit the enzyme linked to Alzheimer’s, supporting its further development as a potential treatment for the disease.
Article Abstract
Introduction: Pyroglutamate-amyloid-β (pE-Aβ) peptides are major components of Aβ-oligomers and Aβ-plaques, which are regarded as key culprits of Alzheimer's disease (AD) pathology. PQ912 is a competitive inhibitor of the enzyme glutaminyl cyclase (QC), essential for the formation of pE-Aβ peptides.
Methods: A randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study investigated the safety, pharmacokinetics, and pharmacodynamics of PQ912 in healthy nonelderly and elderly subjects.
Results: PQ912 was considered safe and well tolerated with dose-proportional pharmacokinetics up to doses of 200 mg. At higher doses up to 1800 mg, exposure was supraproportional and exposure in elderly subjects was approximately 1.5- to 2.1-fold higher. Exposure in cerebrospinal fluid (CSF) was approximately 20% of the unbound drug in plasma, and both serum and CSF QC activity was inhibited in a dose-related manner.
Discussion: This first-in-man study of a compound-targeting QC inhibition justifies further development of PQ912 for the treatment of AD.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975062 | PMC |
| http://dx.doi.org/10.1016/j.trci.2015.08.002 | DOI Listing |
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