Rapamycin and its analogs as novel treatments for hemangiomas
Inventors: Joyce Bischoff, Shoshana Greenberger
Invention Types: Therapeutics
Research Areas: Dermatology, Neonatology/Pediatric
Keywords: Disease Model, Drug Screening, New Indication/Use, DermatologicFor More Information Contact: Ives, Catherine L.
Infantile hemangiomas (IH) are benign endothelial tumors composed of disorganized blood vessels which appear within the first month of life and will continue to grow for up to 12 months. The tumors eventually begin to slowly regress over 1 to 7 years, but this period of involution and its extent are extremely variable. Most hemangiomas do not regress to an acceptable cosmetic level on their own. They occur most often in the head and neck region but they may occur anywhere on the skin or internal organs, and can lead to cardiac failure, hemorrhage and jaundice in addition to disfigurement. Dr. Bischoff's lab developed unique patient-derived cellular and animal models of IH in collaboration with BCH's Vascular Anomalies Center, the largest center of its kind in the world. With these assays, Dr. Bischoff and colleagues carried out a screen for FDA-approved drugs that could serve as novel treatments for IH. They found that rapamycin and rapamycin analogues alone or with steroids have beneficial effects in IH.
Between 4% and 10% of Caucasian infants have at least one hemangioma; most remain small and pose no serious threat to the infant but about 10% of these become clinically significant. The incidence increases to 1 in 5 in premature infants. Problematic hemangiomas are high sources of morbidity and can cause psychosocial complications. Work in IH teaches us about mechanisms such as vasculogenesis, angiogenesis and tissue remodeling, which are applicable to more commonly occurring conditions.
Severe IH is an area of high unmet medical need. Current standard of care is corticosteroids but these can have serious side effects and 30% of children do not respond. Propranolol was discovered serendipitously to be effective and safe, and has rapidly gained acceptance as a treatment modality. Other established treatment options include vincristine, as well as laser and surgical interventions, and are used with variable results. Rapamycin and rapamycin analogues could represent new therapeutic strategies for IH. Dr. Bischoff is continuing to study these agents in IH and is interested in investigating potential combination treatments of rapamycin both in the lab and in the clinic. In collaboration with the Vascular Anomalies Center at CHB, they are actively pursuing development of a phase 1/2 clinical trial of combination treatment with rapamycin in IH.
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Key Publications: Greenberger S, et al. Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma. J Invest Derm. 2011 Dec;131(12)
Related Publications: Huang L, et al. Glucose transporter 1-positive endothelial cells in infantile hemangioma exhibit features of facultative stem cells. Stem Cells. 2015 Jan;33(1)
IPStatus: Pat. Pend.