Serum biomarkers for diagnosis and sirolimus response in lymphangioleiomyomatosis

Awardee: Elizabeth P Henske

Institution: Brigham and Women's Hospital, Harvard Medical School

Grant Amount: $73,958

Funding Period: February 1, 2025 - January 31, 2026


Summary:

Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women. Diagnosis is often difficult and sometimes requires lung biopsy, which can be associated with significant morbidity. Vascular endothelial growth factor D (VEGF-D) is increased in the blood of some women with LAM and can serve as diagnostic tool, making biopsy unnecessary. However, about one-third of women with LAM have low levels of VEGF-D. Furthermore, additional biomarkers are needed to predict and monitor the clinical response to sirolimus, the only FDA-approved treatment for LAM. In this project, we will use SomaScan, a high-throughput platform, to measure the blood levels of more than 10 000 proteins in less than a drop of blood. The SomaScan analyses will be performed before and after the start of sirolimus therapy and in matched healthy control women. We will identify biomarkers that are elevated in LAM as compared to the control population and can thus help to diagnose LAM. We will also identify biomarkers that change after sirolimus therapy and can thus be used as surrogates of treatment response. Overall, this project will use a high-throughput platform to identify novel blood biomarkers to improve the diagnose of LAM and predict the response to sirolimus treatment.

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Deciphering the role of ephrin B2 mutation in the pathogenesis of central conducting lymphatic anomaly

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Deciphering the splicing order of COL6A1-3 pre-mRNAs to improve the prognosis and treatment of collagen VI-related muscular dystrophies