Biomarkers for Diagnosing Infantile Hemangiomas and Other Vascular Malformations
Endothelial and circulating C19MC microRNAs as biomarkers of infantile hemangioma
Dr. Perkins is focused on surgical and medical therapies for vascular malformations, which are congenital anomalies involving veins, arteries, or the lymphatic system. Of particular interest are infantile hemangiomas (IHs), benign vascular tumors that develop rapidly in infants. IHs often resolve on their own over time but they may potentially block airways, become disfiguring, or impair chewing, eating or speaking, as well as interfere with quality of life. Therefore, resolving IHs with the least invasive treatment possible is a priority. Also of interest are other head and neck vascular malformations that can involve tumors, bleeding, or swelling in the mouth, tongue, face or neck.
In recent years, Perkins has pioneered propranolol treatment to reduce or prevent the growth of IH tumors without the risk of surgery. Propranolol is a β-adrenergic receptor antagonist, known for the treatment of high blood pressure and other cardiac diseases. However, because some IHs do not respond to propranolol, there is a need to improve diagnostic specificity and treatment.
Perkins and his team have identified a microRNA biomarker for diagnosis of IH. By analyzing the microRNA profile of IH patient samples as compared to other vascular malformations and normal skin tissue, C19MC was identified as a microRNA cluster only over-expressed in IH endothelial cells. Since microRNAs are also released from their cells of origin into circulation, C19MC microRNA is detectable in plasma of IH patients. Perkins’ team has demonstrated that C19MC microRNA is present in plasma of IH patients before treatment with propranolol and is lowered or undetectable after successful treatment.
The development of a diagnostic biomarker for IH is important because diagnosis of a vascular malformation can be difficult. The presence of C19MC microRNA can help confirm an IH diagnosis without the need for a biopsy. Furthermore, this biomarker might be used in the future to help determine the optimal dosage of propranolol, guide treatment, measure responses, and improve patient outcomes.
Perkins is interested in collaborations aimed at improving diagnosis and treatment of IH and other vascular malformations. He is interested in determining the mechanism of action of propranolol as an effective therapy for IH and finding microRNA-based therapies that may combine with propranolol to improve IH treatment. Additionally, he is interested in determining the microRNA signatures of other vascular malformations to develop other diagnostic biomarkers like C19MC microRNA.
Stage of Development
- Pre-clinical in-vitro
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Sample Access
- Diagnostic Service
- Strub GM, Kirsh AL, Whipple ME, Kuo WP, Keller RB, Kapur RP, Majesky MW, Perkins JA. Endothelial and circulating C19MC microRNAs are biomarkers of infantile hemangioma. JCI Insight. 2016 Sep 8;1(14):e88856. doi: 10.1172/jci.insight.88856.
- Kirkham EM, Edwards TC, Weaver EM, Balakrishnan K, Perkins JA. The Lymphatic Malformation Function (LMF) Instrument. Otolaryngol Head Neck Surg. 2015 Oct;153(4):656-62. doi: 10.1177/0194599815594776. PMID: 26195574
- Luks VL, Kamitaki N, Vivero MP, Uller W, Rab R, Bovée JV, Rialon KL, Guevara CJ, Alomari AI, Greene AK, Fishman SJ, Kozakewich HP, Maclellan RA, Mulliken JB, Rahbar R, Spencer SA, Trenor CC 3rd, Upton J, Zurakowski D, Perkins JA, Kirsh A, Bennett JT, Dobyns WB, Kurek KC, Warman ML, McCarroll SA, Murillo R. Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA. J Pediatr. 2015 Apr;166(4):1048-54.e1-5. doi: 10.1016/j.jpeds.2014.12.069. PMID: 25681199
- Perkins JA, Chen BS, Saltzman B, Manning SC, Parikh SR. Propranolol therapy for reducing the number of nasal infantile hemangioma invasive procedures. JAMA Otolaryngol Head Neck Surg. 2014 Mar;140(3):220-7. doi: 10.1001/jamaoto.2013.6524.PMID: 24557492