2024-03-29T13:49:44Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1522422022-06-23T11:19:30Zcom_10261_86com_10261_1col_10261_339
Repurposing propranolol as a drug for the treatment of retinal haemangioblastomas in von Hippel-Lindau disease
Albiñana, Virginia
Jiménez Escribano, Rosa María
Soler, Isabel
Rodríguez Padial, Luis
Recio-Poveda, Lucía
Villar Gómez de las Heras, Karina
Botella, Luisa María
Ministerio de Economía y Competitividad (España)
Fundación Iberdrola
Bodegas Protos
Fundación PortAventura
Alianza española de familias de von Hippel-Lindau
von Hippel-Lindau disease (VHL)
pVHL
Hypoxia inducible factor
Retinal haemangioblastoma
Juxtapapillary and peripheral haemangioblastoma
Propranolol
Beta-blockers
[Background]
Von Hippel-Lindau (VHL) disease is a rare oncological disease with an incidence of 1:36,000, and is characterized by the growth of different types of tumours. Haemangioblastomas in the central nervous system (CNS) and retina, renal carcinoma and pheochromocytomas are the most common tumours. The absence of treatment for VHL leads to the need of repeated surgeries as the only option for these patients. Targeting VHL-derived tumours with drugs with reduced side effects is urgent to avoid repeated CNS surgeries. Recent reports have demonstrated that propranolol, a β-blocker used for the treatment of hypertension and other cardiac and neurological diseases, is the best option for infantile hemangioma (IH). Propranolol could be an efficient treatment to control haemangioblastoma growth in VHL disease given its antiangiogenic effects that were recently demonstrated by us. The main objective of the present study was the assessment of the efficacy and safety of propranolol on retinal haemangioblastoma in von Hippel-Lindau disease (VHL).
[Methods]
7 VHL patients, from different regions of Spain, affected from juxtapapillary or peripheral haemangioblastomas were administered 120 mg propranolol daily. Patients were evaluated every 3 months for 12 months, at Virgen de la Salud Hospital (Toledo). The patients had juxtapapillary or peripheral haemangioblastomas but had refused standard treatments.
[Results]
Propranolol was initiated with a progressive increase up to a final dose of 120 mg daily. All tumours remained stable, and no new tumours appeared. The reabsorption of retinal exudation was noted in the two patients having exudates. No adverse effects were recorded. VEGF and miRNA 210 levels were monitored in the plasma of patients as possible biomarkers of VHL. These levels decreased in all cases from the first month of treatment.
[Conclusions]
Although more studies are necessary, the results of this work suggest that propranolol is a drug to be considered in the treatment of VHL patients with retinal haemangioblastomas. VEGF and miRNA 210 could be used as biomarkers of the VHL disease activity.
[Trial registration]
The study has a clinical trial design and was registered at EU Clinical Trials Register and Spanish Clinical Studies Registry, EudraCT Number:
2014–003671-30
. Registered 2 September 2014.
This work was supported by grants SAF2011–23475 and SAF2014–52374-R from Ministerio de Economía y Competitividad, from Alianza VHL Spain, Fundación Iberdrola, Bodegas Protos and Fundación Port Aventura. Virginia Albiñana was supported by Alianza VHL Spain.
2017-07-02T03:18:32Z
2017-07-02T03:18:32Z
2017-06-29
2017-07-02T03:18:32Z
artículo
http://purl.org/coar/resource_type/c_6501
Orphanet Journal of Rare Diseases 12(1): 122 (2017)
1750-1172
http://hdl.handle.net/10261/152242
10.1186/s13023-017-0664-7
http://dx.doi.org/10.13039/501100003329
28662711
http://dx.doi.org/10.1186/s13023-017-0664-7
open
BioMed Central