Uniwersytet Jagiellonski

Research finds a nearly 40% decline in the annual average concentration of respirable particulate matter (PM2.5) in Krakow, Poland, between 2010 and 2019 following the implementation of clean air policies. Air quality improvements translated to substantial benefits for children's outcomes, including fewer cases of asthma and better birth outcomes. Residential heating by coal has for decades been the major contributor to the high levels of air pollution in Kraków, Poland. New research finds a nearly 40 percent decline in the annual average concentration of respirable particulate matter (PM2.5) in Kraków, Poland, between 2010 and 2019 following the implementation of policies targeting emissions from the burning of coal and other solid fuels. Researchers show the improvement in air quality translated to substantial benefits for children's outcomes, including fewer cases of asthma and better birth outcomes. The findings by researchers at Columbia University Mailman School of Public Health and Jagiellonian University Medical College in Krakow appear in the journal Environmental Research Letters. The researchers modeled health gains that would have occurred in 2010 if PM2.5 had been at the lower level achieved in 2019 through policy changes The benefits included 505 fewer new cases of asthma in the 1-14 age group (a 35.7% decline), 81 fewer preterm births (16.8% decrease), and 52 fewer cases of low birth weight (12.3% decrease). They also modeled gains based on a second hypothetical, which assumed that city had adhered to the WHO's 2005 guidelines on PM2.5. They found this scenario of a 74% reduction in PM2.5 would have avoided 780 new asthma cases in the 1-14 age group (54.5% decrease), 138 preterm births (28.3% decrease), and 90 cases of low birth weight (21.2% decrease). In 2021, Krakow was ranked 28th out of 858 European studies in air pollution related-mortality in the ISGlobal-Ranking of Cities survey. These high levels of pollution have been attributed largely to the use of coal-burning ovens in residential spaces, and to a lesser extent transportation and power plant emissions. Government interventions, including a co-financing program to replace coal-burning stoves in the 1990s, markedly improved the city's air quality, positively impacting children's health outcomes. However, according to researchers, levels of human-derived air pollution, such as emissions from motor vehicles, is still a concern. "Fetuses, infants, and children are uniquely vulnerable to air pollution," explains study senior author Frederica Perera, PhD, DrPH, professor of environmental health sciences and director of translational research at the Columbia Center for Children's Environmental Health at Columbia Mailman, "Our results show very large benefits can be achieved for children's health by curbing fossil fuel emissions." "This is one of the first studies describing the impact of pollution on the Polish pediatric population," noted study first author Agnieszka Pac, MSc., PhD, chair of Epidemiology and Preventive Medicine at Jagiellonian University Medical College, Krakow, Poland. "New policies must take into account children's health, especially given that children often engage in vigorous outdoor activities, making them vulnerable to higher doses of pollutants." In earlier studies, the researchers reported a significant improvement in air quality based on personal air monitoring in our Kraków cohort study of pregnant women and their children based on personal air monitoring. They also identified links between air pollution exposure and birth outcomes, growth trajectories, lung function, developmental delays, behavioral problems, and cancer risk. Additional authors of the new study include Renata Majewska, Natalia Nidecka, and Elzbieta Sochacka-Tatara from Jagiellonian University Medical College. This study was supported by a grant from an anonymous foundation.

Princeton, NJ, October 20, 2023 ─ iQure Pharma Inc. (iQure), a CNS company dedicated to the development of new epilepsy and pain management therapeutics, has completed the first closing of its latest round of funding. The company has raised $1.2M to progress with IND-enabling pivotal tox studies for its lead asset iQ-007, a first in class EAAT2 PAM neuromodulator. iQ-007 is a novel therapeutic candidate to treat epilepsy and other neurodegenerative conditions. The round was led by Munich-based life science fund Ventura BioMed Investors and anchor early-stage med-tech investor OKG Capital. Both investors see this round as a first step towards further funding to complete preclinical development and start Phase 1 trials. iQure's leading compound, iQ-007, is a neuromodulator targeting toxic levels of glutamate in the synaptic cleft. An elevated level of glutamate leads to neurotoxicity and ultimately to neural degeneration. iQ-007 operates by a Positive Allosteric Modulation of Excitatory Amino Acid Transporter 2 (EAAT2 PAM), which is responsible for up to 90% of glutamate uptake. A decrease in EAAT2 function is observed in epilepsy, stroke, Alzheimer's disease, neuropathic pain and ALS. Preclinical in vivo efficacy and safety data strongly support the potential value of this compound for patients suffering from epilepsy, including those who have seen limited success with seizure control using existing medications. iQ-007 has successfully completed the prestigious NIH ETSP epilepsy screening program and pivotal tox studies are ongoing. The Company is looking to start clinical development of iQ-007 in 2024. “Addressing neurodegeneration and preventing seizures in an effective and safe manner is a critical medical and social need,” said iQure CEO Pawel Zolnierczyk. “Epilepsy alone affects over 50 million people worldwide and approximately 30% of them struggle to control their seizures using current medication. Many also suffer from reduced quality of life due to medication side effects. In addition, aging populations are contributing to a surge in neurodegenerative diseases such as Alzheimer's and Parkinson's, with over 55 million people currently suffering from dementia, and 10 million new cases identified every year. “Securing funding from life science focused investors Ventura BioMed Investors and OKG Capital is a major milestone and will accelerate our clinical development,” said Zolnierczyk. “We also want to thank leading global CNS researcher Professor Krzysztof Kaminski and Jagiellonian University in Poland, who are instrumental in the ongoing development of iQ-007, for their close and successful collaboration. We are looking forward to bringing iQ-007 to clinical development in 2024.” About iQure Pharma iQure Pharma, a global biotech firm headquartered in the US, is focused on the development of new therapeutics for CNS, including neuropathic pain, epilepsy and other neurodegenerative diseases. iQure researchers, clinicians, and pharmaceutical professionals work closely with academic partners, industry experts, and patient organizations to build medically and socially beneficial therapies. About Ventura BioMed Investors Ventura BioMed Investors invest in early-stage life science companies developing pioneering technologies and innovative therapies. As serial entrepreneurs with many years of experience, we help shape the long- term development of our portfolio companies and provide them access to our broad investor and business network. Ventura BioMed Investors supports exceptional entrepreneurs with their vision to accelerate medical breakthroughs that solve unmet patient needs. About OKG Capital OKG Capital is a specialist med-tech and life science investor based in the US with operations in London and Geneva. OKG invests in the management and diagnosis of serious chronic diseases affecting individuals and burdening healthcare systems. OKG aims to bridge the gap between cutting edge science and clinical practice, operating at the intersection between patient need and long-term financial return.

A potent plant toxin with a unique way of killing harmful bacteria has emerged as one of the strongest new antibiotic candidates in decades. A potent plant toxin with a unique way of killing harmful bacteria has emerged as one of the strongest new antibiotic candidates in decades. The antibiotic, called albicidin, is produced by the bacterial plant pathogen Xanthomonas albilineans, which causes the devastating leaf scald disease in sugar cane. Albicidin is thought to be used by the pathogen to attack the plant, enabling its spread. It has been known for some time that albicidin is highly effective at killing bacteria including E. coli and S. aureus. These superbugs, notorious for their growing resistance to existing antibiotics, have prompted a vital need for effective new drugs. Despite its antibiotic potential and low toxicity in pre-clinical experiments, pharmaceutical development of albicidin has been hampered because scientists did not know precisely how it interacted with its target, the bacterial enzyme DNA gyrase (gyrase). This enzyme binds to DNA and, through a series of elegant movements, twists it up, a process known as supercoiling which is vital for cells to function properly. Now, Dr Dmitry Ghilarov's research group at the John Innes Centre, alongside the laboratories of Prof. Roderich Süssmuth at Technische Universität Berlin, Germany and Prof. Jonathan Heddle at Jagiellonian University, Poland, have exploited advances in cryo-electron microscopy to obtain a first snapshot of albicidin bound to gyrase. It showed that albicidin forms an L-shape, enabling it to interact with both the gyrase and the DNA in a unique way. In this state gyrase can no longer move to bring the DNA ends together. The effect of albicidin is akin to a spanner thrown between two gears. The way albicidin interacts with gyrase is sufficiently different from existing antibiotics that the molecule and its derivatives are likely to be effective against many of the current antibiotic resistant bacteria. "It seems by the nature of the interaction, albicidin targets a really essential part of the enzyme and it's hard for bacteria to evolve resistance to that," said Dr Ghilarov. "Now that we have a structural understanding, we can look to further exploit this binding pocket and make more modifications to albicidin to improve its efficacy and pharmacological properties." This work has already begun: the team used their observations to chemically synthesise variations of the antibiotic with improved properties. In tests, these variants were effective against some of the most dangerous hospital-acquired bacterial infections including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhimurium. Dr Ghilarov said: "We believe this is one of the most exciting new antibiotic candidates in many years. It has extremely high effectiveness in small concentrations and is highly potent against pathogenic bacteria -- even those resistant to the widely used antibiotics such as fluoroquinolones." "This molecule has been around for decades," continued Dr Ghilarov, "Now advances in cryo-electron microscopy has made it possible to determine structures of even the most elaborate protein-DNA complexes. To be the first person to see the molecule bound to its target and how it works is a huge privilege, and the best reward one can have as a scientist. But this work is a big team effort, and we would not have done it without our European colleagues." The next step for this research is to engage with academic and industrial collaborators, and to seek funding to take the research forward to human clinical trials. This could lead to the development of an urgently needed new class of antibiotics in the face of a global threat of antimicrobial resistance, AMR. Albicidin -- how does it work? Albicidin targets an enzyme found in both plants and bacteria called DNA gyrase (or simply "gyrase"). This enzyme binds to DNA and, through a series of elegant movements, twists it up (a process known as supercoiling) -- a vital process for cells to function properly. However, gyrase has an Achilles heel; to do its job it must momentarily cut the DNA double helix. This is dangerous, as broken DNA is lethal to the cell. Normally, gyrase quickly joints the two pieces of DNA back together again as it works, but albicidin prevents it from happening, resulting in broken DNA and bacterial death. About Anti-Microbial Resistance (AMR) Multi-drug resistant pathogens such as Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium present a dangerous healthcare burden, exacerbated by the COVID-19 pandemic. Infections by resistant pathogens are a leading cause of death in hospital intensive care units, with some strains becoming pan resistant. Gram-negative drug-resistant pathogens were a cause of 50,000 deaths in 2019. Despite urgently needed new medicines to combat this threat, drug discovery programmes have yielded no new classes of antibiotics for several decades.