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Accelerating Therapies


Pulmonary Fibrosis is a disease with a significant unmet medical need. Three Lakes Foundation is committed to identifying and addressing gaps in the areas of disease pathogenesis, diagnosis, and novel therapies.

Our Projects


The emerging field of precision medicine aims to identify the best ways to prevent and treat disease in individuals or specific groups given their genetic profiles, environments, and lifestyles - giving practitioners more power to predict which treatment and prevention strategies for a specific disease will work in which people.

The National Institutes of Health (NIH) and Three Lakes Foundation are funding the first molecular-based precision medicine research study designed to transform the diagnosis and treatment of interstitial lung diseases (ILD), particularly idiopathic pulmonary fibrosis (IPF).

The study, conducted in partnership with the Pulmonary Fibrosis Foundation, is known as Precisions (Prospective tReatment EffiCacy in IPF uSIng genOtype for Nac Selection). Its goals are:

• Determine if N-Acetyl-cysteine (NAC) is an effective treatment for a subgroup of IPF patients with a particular gene variant.
• Distinguish IPF from non-IPF interstitial lung diseases using advanced molecular techniques and proteomics to analyze blood samples.
• Identify genetic variants that influence IPF risk.

The results from this study are important since risk scores associated with disease subtypes may help doctors diagnose patients as well as predict their prognosis and potential response to therapy.

Novel Diagnostics Owlstone Medical

Pulmonary Fibrosis is difficult to diagnose without the common use of invasive methods. Recent research has revealed that volatile organic compounds (VOCs) present in exhaled breath may be biomarkers of certain diseases, including PF. Three Lakes Foundation's 2018 IPF Catalyst Challenge winner, Owlstone Medical, has developed the ReCIVA Breath Sampler, which ensures a reliable, reproducible collection of VOCs from patient breath samples, which can then be profiled using mass spectrometry (GC-MS) to pinpoint the VOCs of interest. An ongoing study is designed to identify a PF diagnostic signature that can be used for early detection of PF.

SINGLE CELL ATLAS DR. IVAN ROSAS, Pulmonary, Critical care and Sleep Medicine, Baylor College of Medicine. DR. NAFTALI KAMINSKI, Pulmonary, Critical care and Sleep Medicine, Yale University School of Medicine

Our partnership with the Rosas and Kaminski labs on the Pulmonary Fibrosis Cell Atlas generated valuable data and insights that are now available to all investigators advancing treatments for PF. To develop effective therapies for PF, we need to understand all of the cellular changes happening in the human lung as fibrosis develops. Specifically we need to define the changes in resident and infiltrating cells, identifying emergent novel and ectopic cell types, and map the altered cell-cell communications as this would allow developing interventions that will stop or reverse fibrosis. The Rosas and Kaminski labs used state-of-the-art technologies to create viable single cell lung suspensions from IPF tissues, and generated high throughput profiles of all cells in the IPF lung at the single cell resolution using single cell RNA sequencing. Using advanced computational methods, the researchers identified evidence for novel aberrant and ectopic cell populations in the IPF lung and generated a catalogue of all the phenotypic changes in all lung cells in the disease. This resulted in the creation of the IPF Cell Atlas ( data dissemination portal that allows free mining and exploration of the data to accelerate the development of novel therapies in PF.

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CleanUP STUDY (Clinical Efficacy of Antimicrobial Therapy Strategy Using Pragmatic Design in Ideopathic Pulmonary Fibrosis) DR. FERNANDO MARTINEZ WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY

The CleanUP IPF study is part of the Pulmonary Trials Cooperative (PTC) established by the National Heart, Lung, and Blood Institute (NHLBI). The PTC is a collaborative network of investigators and clinical centers that are conducting research and developing novel therapies to improve the outcomes of patients with chronic pulmonary diseases. Past research indicates that IPF patients treated with the antimicrobials co-trimoxazole (Bactrim) or doxycycline may have improved clinical outcomes. The CleanUP IPF trial is designed to confirm whether antimicrobial therapy plus standard of care will improve clinical outcomes such as the length of time to a rehospitalization and mortality in patients with PF. The study work is being conducted with over 500 subjects at 31 research institutions across teh U.S. and includes a pragmatic randomized trial design and collection of data that will be used to develop future personalized therapies.

New Drug Development Dr. Philip Low, Purdue University

The Low Lab at Purdue University is working to identify and validate novel therapies for pulmonary fibrosis. The lab has unique experience in the development of targeted molecules called small molecule drug conjugates (SMDC), which deliver compounds directly to the cells that develop and perpetuate IPF. Developing these compounds requires a specific small molecule, an optimized linker, and a ligand specific for the cells being targeted. Finding the proper combination of these three parts is challenging, but with its proven expertise, the Low Lab, a global leader in targeted therapies, continues to drive this development forward.