The LAM Foundation Patient Benefit Grants
In November 2017, The LAM Foundation held the first-ever LAM Patient Benefit Conference, an innovative meeting where patients, scientists, clinicians and innovators collaborated to find science-driven solutions to important lifestyle, and mental and physical health issues that LAM patients identified as most important and relevant to them. The main goal of the conference was to frame ideas new products or services with the potential to benefit LAM patients in the shorter term: five years or less.
In advance of the event, The LAM Foundation conducted two surveys – one for LAM patients, and one for LAM clinic directors. The collective feedback of 250 patients and 16 clinic directors enabled The LAM Foundation to identify the following six topics that were addressed at the conference:
- Biomarkers and Imaging for LAM
- Supplemental Oxygen and LAM
- Exercise and LAM
- Coping and Mental Wellness
- The Clinic Experience and Patient Reported Data
Through moderated solutions workshops utilizing Design Thinking concepts, patients, researchers, clinicians and thought leaders discussed how to cultivate solutions for each of these topics. The outcomes were presented at the closing plenary where patients voted to prioritize ideas, projects and directions. The momentum of this stimulating meeting was taken to the LAM Breath of Hope Gala and nearly $200,000 in funds were raised for a newly established Patient Benefit Grant Program.
Carmen Priolo, MD PhD
Harvard Medical School
Brigham and Women's Hospital
Feasibility Study of [11C]acetate PET as an Indicator of Early Response to Rapamycin in LAM Patients
Our goal is to test the potential for [11C]acetate positron emission tomography (PET) as a biomarker of whole-body tumor burden and metabolic activity in patients with sporadic or TSC-associated LAM. This imaging methodology is FDA-approved for cardiac diseases and therefore has been proven to be safe for humans. It is a whole-body imaging technique that uses radiolabeled acetate to non-invasively detect (visualize and quantify) body cells that have an increased utilization of this nutrient, specifically TSC2-deficient cells.
This study may have large applicability in the diagnostics of both LAM and TSC. Sensitive imaging modalities to detect the metabolic activity of TSC2-deficient tumors would be critical in clinical trials to test the efficacy of new agents and would help clinical-decision making during follow-up of LAM and TSC patients, including assessment of rapamycin dosage.
Adam G. Cole, MD
University of Cincinnati College of Medicine
Impact of Menstrual Cycle Related Variation in Lung Function on Disease Progression in LAM
Hormonal influences are believed to play a pathogenic role in lymphangioleiomyomatosis (LAM) as suggested by the following observations: symptomatic LAM is restricted almost exclusively to females, LAM is exacerbated by exogenous estrogen use and pregnancy, and premenopausal patients decline faster than postmenopausal patients. However, the exact role of hormones in the pathogenesis of LAM remains elusive, and hormonal therapies are not currently recommended. The correlation of cyclical fluctuations in lung function and pulmonary symptoms during the menstrual cycle will provide strong circumstantial evidence for the role of hormones in the pathogenesis of LAM and allow us to address our hypothesis that menstrual variation is a sub-phenotype of LAM that is associated with more rapid progression and should be considered for earlier intervention. If the cohort of LAM patients with menstrual cycle variability in FEV1 demonstrates a more rapid decline in lung function, then menstrual cycle variation in home spirometry could become a novel prognostic biomarker that could help guide our decision-making process to select candidates for earlier treatment initiation. Additionally, this group might benefit from hormonal treatment and could enrich future clinical trials of hormonal agents for LAM. If validated by this project, home spirometry could function as an end point in such a trial.
Anne-Karina T. Perl, MS, PhD
Cincinnati Children’s Hospital Medical Center
Identification and Validation of New Biomarkers Based on Single Cell Rnaseq Data
Aside from serum VEGF-D, which has shown value as a diagnostic biomarker for LAM, very few other molecular biomarkers exist. There is a critical need to develop novel biomarkers, especially prognostic and predictive biomarkers that can aid in determination of disease progression and response to treatment, respectively. We will use existing single cell RNAseq data to identify new biomarkers and molecular targets and validate their expression in LAM cells and LAM lungs. This approach will allow us to develop pathophysiology-based, LAM-specific diagnostic, prognostic, and predictive biomarkers.
Jane J. Yu, PhD
University of Cincinnati College of Medicine
Single-Cell-RNA Sequencing for Identifying Differential Responses to Sirolimus Therapy in LAM
A major impediment to a cure for LAM is that even though sirolimus is effective for most, some patients continue to progress on therapy. We need to understand how the LAM cell evades the actions of sirolimus, including the activation of signaling pathways, or downregulation of inhibitory feedback loops. An understanding of the LAM cell response to sirolimus exposure will reveal new approaches to the treatment of hyporesponsive or resistant patients, identify biomarkers that herald resistance before irreversible lung function decline occurs, and suggest remission inducing treatment strategies.
Mary Beth Brown, PT, PhD
University of Washington School of Medicine
Mobile Health to Increase Patient Accessibility to Exercise and Elucidate Exercise & Fatigue in LAM
We will develop a mobile health platform to initiate the first ‘library’ of patient data related to exercise and fatigue in LAM. The web-based platform will interface with patient-worn devices for monitoring heart rate, blood oxygen levels, and physical activity levels, and will also link with patient recorded values for pulmonary function, supplemental oxygen use, symptoms of fatigue and shortness of breath, and sleep quality. This catalogue of data will allow researchers to understand factors contributing to exercise intolerance and fatigue in LAM, and how to prescribe optimal exercise for patients. Its value will continue to increase even after the project has concluded, since the database will grow with each patient that participates and each month of collection that passes. A 2nd purpose for developing this mobile health platform is to use it to direct an exercise study where we investigate if a home exercise program paired with smartphone coaching and monitoring is effective as an alternative to supervised pulmonary rehabilitation for LAM patients. By obtaining a small sample of leg muscle from patients we will also obtain insight into muscle abnormalities that contribute to the problem of exercise tolerance and fatigue in LAM and how these abnormalities may be improved with exercise training. Findings from this project will be utilized to construct guidelines for management of exercise intolerance and fatigue in LAM including optimal exercise approach for patients.