Principles of the Strategic Scientific Plan
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that is associated with cystic destruction of the lung, recurrent pneumothorax, abdominal tumors including angiomyolipomas and lymphangioleiomyomas, lymphatic spread, chylous fluid accumulations, and progressive respiratory insufficiency. Although long classified as an idiopathic interstitial lung disease, a decade of research has revealed that LAM is actually a low-grade, metastatic neoplasm caused by growth promoting mutations in tuberous sclerosis complex (TSC) genes. Lymphangiogenic processes are also activated by the TSC mutations, providing a mechanism for dissemination and destructive tissue remodeling by the otherwise innocent-appearing neoplastic LAM cells. The connections between LAM and TSC, cancer, and central pathways that control cellular metabolism have greatly enhanced interest in the disease, and have enabled the LAM community to attract some of the world’s most accomplished scientists and pharmaceutical companies to the field.
The LAM Foundation is the largest funder of LAM research, outside of the National Institutes of Health. Since 1995, The Foundation has committed nearly $11.5 million to LAM research, the majority of which has supported 149 peer-reviewed grants and translational projects. LAM Foundation-funded scientists reported several major discoveries, including evidence that LAM is genetic, the identification of a LAM gene, and a molecular explanation for abnormal smooth muscle cell growth in LAM. This data led to the identification of a therapy for LAM called sirolimus, or rapamycin, with clinical trial results published in the April 2011 issue of the New England Journal of Medicine (NEJM). Several additional molecular targets have been identified, many of which are addressable with drugs that are FDA-approved for other indications.
LAM is in an uncommon research position among human diseases that requires innovative planning; we have a large body of cellular and molecular knowledge which we anticipate will continue to rapidly accumulate with funding from federal sources, no optimal cell or animal models, and a limited pool of patients available for trials. LAM Foundation research will therefore be focused on the development and validation of drug targets, prioritization of compounds for testing, and facilitation and implementation of phase I/II clinical trials. This strategy will require closer partnerships with industry and with the NIH.
The following principles will guide The LAM Foundation Research Program going forward:
- Research will remain the central mission of the Foundation.
- Our basic research funding will continue to be based on peer-reviewed, investigator-initiated research.
- Translational studies that help bring bench discoveries to the bedside are a priority, especially those focused on development of targets for LAM trials and studies that link pivotal findings in critical, parallel research arenas (e.g., TSC) to LAM.
- Our clinical research goal is “a trial for every LAM patient and every LAM patient in a trial.” Research resources will be directed toward development of biomarkers and small phase I/II trials.
- We remain committed to the development of LAM cell and animal models.
- Letters of intent will be required for submission of LAM Foundation research proposals, to ensure that all studies forwarded for review are aligned with the theme.
- Progress in LAM research will require free access to data, and to human tissue and reagents. We will continue to develop and facilitate systems to acquire and distribute tissue.
- We will increase resources available for research through vigorous fundraising, and partnerships with academia, industry, the NIH, and other foundations and organizations.
- Systems will be developed to measure LAM research outcomes including LAM Foundation citations, attributions, awards, publications, funding successes, accomplishments and discoveries, and use these data to promote the Foundation research program.
- LAM Clinics will be opened in geographically dispersed locations and will be resources for diagnosis, treatment and trials for LAM patients.