KARS

INCHEON, South Korea, Feb. 7, 2024 /PRNewswire/ -- Zymedi announced today that the first in human dosage of ZMA001, a monoclonal antibody being developed as a first-in-class treatment for Pulmonary Arterial Hypertension (PAH) has been initiated. The placebo-controlled phase 1 trial designed to ascertain the safety and dosage of ZMA001 is a collaborative effort between Zymedi and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH). In the preceding year, both organizations entered into a Cooperative Research & Development Agreement (CRADA) in order to work together to advance the development of ZMA001. PAH is a serious and life-threatening condition affecting approximately 3 persons per 100,000 globally, with about 500 to 1,000 new cases diagnosed annually in the U.S. It is characterized by the narrowing of pulmonary arteries, a rise in pulmonary vascular resistance, and eventually death due to right heart failure. Current treatments for PAH, such as vasodilators, reduce symptoms but do not treat the underlying cause of the problem. ZMA001 is a first-in-class therapeutic antibody targeting the novel pro-inflammatory factor KARS1 that is specific to monocytes and macrophages. It can improve both the survival rates and the quality of life of PAH patients by eliminating the root pathologic cause of PAH. "We are excited to initiate this first in human trial of ZMA001, which marks a significant milestone for our company and the fight against PAH," said Dr. Sunghoon Kim, CEO and Founder of Zymedi. "We are scheduled to assess the safety and tolerability of ZMA001 through dose escalation clinical trials, systematically observing adverse reactions as dosage increases. Furthermore, we aim to establish the recommended dosage and determine the Maximum Tolerated Dose (MTD) for forthcoming phase 1b/2a clinical trials involving patients." The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About ZMA001 ZMA001 is a human monoclonal antibody designed to control or inhibit inflammation responses in pulmonary blood vessels by blocking lysyl-tRNA synthetase (KARS1)-dependent infiltration of monocytes and macrophages. ZMA001 specifically targets membrane-exposed KARS1 without affecting its catalytic activity for protein synthesis. It can assure specificity toward response, disease indication, immune system, and target biology without inducing the systemic hypotension frequently observed with other typical treatments using vasodilators. ZMA001 with its novel MOA, is expected to treat PAH by eliminating its root pathologic cause unlike other treatments such as vasodilators that only address the symptoms. About Zymedi Zymedi is a global biopharmaceutical company that is committed to transforming the role of ARSs (Aminoacyl-tRNA Synthetases) and targeting it as a method of discovering and developing innovative treatments for patients with serious and life-threatening conditions that have no standard of care or lack effective therapy. For more information, please visit SOURCE Zymedi

Scientists at the University of California San Diego, along with colleagues in Australia, engineered bacteria capable of detecting the presence of tumor DNA in a live organism. Previously, bacteria could perform diagnostic and therapeutic functions, according to the UC San Diego website. However, they lacked the ability to identify specific DNA sequences and mutations outside of cells. The researchers say this innovation could create a pathway to new biosensors capable of identifying various infections, cancers and diseases. This “Cellular Assay for Targeted CRISPR-discriminated Horizontal gene transfer,” or “CATCH,” demonstrated success in detecting cancer in the colons of mice. “As we started on this project four years ago, we weren’t even sure if using bacteria as a sensor for mammalian DNA was even possible,” said scientific team leader Jeff Hasty, a professor in the UC San Diego School of Biological Sciences and Jacobs School of Engineering. “The detection of gastrointestinal cancers and precancerous lesions is an attractive clinical opportunity to apply this invention.” The CATCH method can test free-floating DNA sequences on a genomic level, comparing those samples with predetermined cancer sequences. It engineers cells to detect and discriminate cell-free DNA. The researchers say it could offer value in clinical (cancer and infection) and commercial (ecology and industrial) applications. “Many bacteria can take up DNA from their environment, a skill known as natural competence,” said Rob Cooper, the study’s co-first author and a scientist at UC San Diego’s Synthetic Biology Institute. Hasty, Cooper and Australian doctor Dan Worthley collaborated on the idea of natural competence in relation to bacteria and colorectal cancer. They looked into engineering bacteria as new biosensors for deployment inside the gut to detect DNA released from colorectal tumors. The team focused on Acinetobacter baylyi, a bacterium Cooper says features the elements necessary for taking up DNA and using CRISPR to analyze it. “Knowing that cell-free DNA can be mobilized as a signal or an input, we set out to engineer bacteria that would respond to tumor DNA at the time and place of disease detection,” said Worthley, a gastroenterologist and cancer researcher with the Colonoscopy Clinic in Brisbane, Australia. The team designed, built and tested the bacterium as a sensor for identifying DNA from KARS, a gene mutated in many cancers. Using CRISPR designed to discriminate mutant from normal KRAS copies, they programmed the bacterium. According to UC San Diego, that meant only bacteria that had taken up mutant forms of KRAS — found in precancerous polyps and cancers — would survive to signal or respond to the disease. The team based their research on previous methods related to horizontal gene transfer. They say they achieved their goal of applying this concept from mammalian tumors and human cells into bacteria. “It was incredible when I saw the bacteria that had taken up the tumor DNA under the microscope,” Wright said. “The mice with tumors grew green bacterial colonies that had acquired the ability to grow on antibiotic plates.” The researchers now aim to adapt the method with new circuits and different types of bacteria, potentially detecting and treating human cancers and infections. They say it requires more development and refinement as the synthetic biology team at UC San Diego works to optimize the strategy. “There’s a future where nobody need die of colorectal cancer,” said Worthley. “We hope that this work will be useful to bioengineers, scientists and, in the future, clinicians, in pursuit of this goal.”