EE Awards $790,000 in Round 5 Funding for Cystic Fibrosis Research
Emily’s Entourage (EE) is thrilled to announce that four new grants have been awarded to advance Cystic Fibrosis (CF) research and drug development, totaling $790,000 to be given over two years.
“These grants focus on two critical unmet needs for the CF community: therapies that address nonsense mutations of CF and treatments for life-threatening lung infections. At Emily’s Entourage, we remain laser focused on filling those gaps as people with CF, and especially those without targeted therapies, do not have time to wait.”
~ Emily Kramer-Golinkoff, Co-Founder, Emily’s Entourage
GRANT RECIPIENTS:
Development of a Phage Lysin to Kill MRSA in the Nose and Lungs of CF Patients
Vincent A. Fischetti, PhD
The Rockefeller University
Bacterial resistance to current antibiotics is becoming an increasing problem resulting in more morbidity and mortality. In individuals with CF, Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA), is frequently observed and causes infections in the noses that subsequently seed the lungs. In this project, the utility of phage lysins to control MRSA infections will be investigated. Lysins represent an alternative to antibiotics as they use a completely distinct mechanism from antibiotics in order to kill bacteria. For alternative bacterial species, resistance to lysins has not been observed. In addition, lysins can be delivered both systemically and via aerosol. Thus, MRSA-specific lysins may have advantages over conventional antimicrobial approaches, prevent chronic infections, and increase quality of life for people living with CF.
Catalyst for the Cure Strategy: Buying Time: Alternative Targets and Approaches
A Novel Approach to Remove the W1282X Mutation to Increase CFTR Function
Adrian R. Krainer, PhD
Cold Spring Harbor Laboratory
CF is caused by mutations that limit the functionality in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which can lead to respiratory failure. The W1282X nonsense mutation leads to the production of a shorter CFTR gene that is present in low levels, making it partially functional due to a cellular quality-control mechanism called nonsense-mediated mRNA decay. This project utilizes a novel approach that includes targeting pre-mRNA splicing to remove exon 23—the region of the CFTR gene that contains the W1282X mutation—to increase the CFTR gene function in individuals with a W1282X mutation of CF. Thus, this project investigates this strategy by developing synthetic Antisense Oligonucleotides that can induce the skipping of exon 23 of the pre-MRNA sequence in order to achieve increased functionality in the mutated CFTR gene.
Catalyst for the Cure Strategy: Spell Check: Fixing Mutations Through RNA Editing
Novel Personalized Treatment Approaches to Protect Against MRSA in CF
Ami Patel, PhD
The Wistar Institute
People living with CF continue to be susceptible to bacterial infections and typically require extensive antibiotic regimens to maintain clear airways. Infections with methicillin-resistant Staphylococcus aureus (MRSA) are a lifelong challenge and new strategies are needed for control. This application will investigate two novel strategies to fight MRSA. The first approach aims to develop a vaccine for MRSA. Conventional vaccines employ protein fragments from a pathogen to produce an immune response. In contrast, this project will use synthetic DNA and rely on the human body to generate the protein fragment—an approach that has many advantages including activation of antibody and cell-based immunity, and easier drug production and storage. The second approach will develop engineered antibodies against MRSA with enhanced antimicrobial activity relative to endogenous anti-MRSA antibodies. As in the first Aim, this study will use DNA to deliver the genetic information to encode these therapeutic antibodies, a strategy that enables sustained delivery and reduces drug costs. These approaches will initially be developed using a clinical isolate derived from a CF subject. It is anticipated that this personalized approach could be applied for other antimicrobial resistant bacterial pathogens that impact CF.
Catalyst for the Cure Strategy: Buying Time: Alternative Targets and Approaches
Development of a Collection of Anti-MRSA Phages as Alternatives to Antibiotics in CF
David T. Pride, MD, PhD, Robert ‘Chip’ Schooley, MD, Steffanie Strathdee, PhD
University of California San Diego Center for Innovative Phage Applications
Individuals with CF are at great risk to develop recurrent lung infections. These infections are often caused by antibiotic-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA). This project aims to develop a panel of phage targeting MRSA that work collectively towards eliminating or reducing it in the lungs of those with CF. By developing a well-characterized MRSA phage bank, this project will advance rational development of MRSA phage cocktails for use in the management of CF and make this collection widely available to physicians and researchers across the globe to facilitate life-saving phage therapy.
Catalyst for the Cure Strategy: Buying Time: Alternative Targets and Approaches
Since 2011, EE has awarded more than $4.8 million to 21 research projects across the globe. These four research projects comprise the fifth round of grants supported by EE’s Catalyst for the Cure fund, which advances critical research to accelerate therapeutic development for people with nonsense mutations of CF who do not benefit from existing mutation-targeted therapies. Importantly, three of these grants fund infection research, meaning the results could benefit people with any mutation of CF, including but not limited to CF nonsense mutations.
Emily’s Entourage is grateful to the grant recipients and all the dedicated scientists who are leading the charge to fill critical unmet needs and develop cutting-edge therapies for 100% of the CF community, fast and with nobody left behind. To view all awarded research grants, please click here.