Understanding the effects of Sirolimus/Zolendronic acid treatment on bone remodeling activity in patients with Gorham-Stout disease
Awardee: Andrea Del Fattore
Institution: Bambino Gesù Children’s Hospital
Award Amount: $81,965
Funding Period: February 1, 2021 - January 31, 2022
Gorham-Stout disease (GSD) is a rare bone disorder characterized by angiomatous proliferation and progressive bone loss, resulting in the appearance of the so-called “vanishing bone” disease. In our previous study, we characterized the cellular alterations leading to the perturbation of physiological bone remodeling. Indeed, we identified in GSD patients increased ability of osteoclast precursors to differentiate into mature cells and alteration of immune cells. This study seeks to characterize the effects of the treatment with mammalian target of rapamycin (mTOR) inhibitor Sirolimus and bisphosphonate Zolendronic acid on the players of remodeling process, investigating the precursors of bone resorbing osteoclasts and the immune cells.
Sirolimus is known to inhibit lymphangiogenesis and is thought to act on lymphatic tissue within lesions regulating production and leakage of lymph. Furthermore, Sirolimus influences immune cells. Bisphosphonates inhibit osteoclast bone erosion and also exert anti-angiogenic effect. Since Sirolimus and bisphosphonates may have an additive effect, GSD patients were treated with the Sirolimus and Zolendronic acid with the aim to stop the disease progression, inhibiting angiogenesis and osteoclast activity, and stimulating immune cells.
This proposal will be important to monitor the efficacy of the treatment and to identify potential prognostic markers, with the aim to translate the results into a better care of GSD patients.