Science and Research

Treatment with low-dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) can be found in patients suffering from a loss-of-function mutation of the gene encoding for the activin receptor-like kinase 1 (ALK-1), a bone morphogenetic protein (BMP) type 1 receptor. Interestingly, ALK-1 mutations also lead to hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease characterized by arteriovenous malformations (AVMs) leading to potentially life-threatening bleeding complications such as epistaxis. Current therapeutic options for both diseases are limited and often only temporary or accompanied by severe side effects. Here, we report of a patient with a mutation of the ALK-1 gene suffering from both HHT and PAH. Recently, it was shown that tacrolimus increased ALK-1 signaling and had beneficial effects in selected end-stage PAH patients. We thus hypothesized that treatment with tacrolimus may prevent disease progression in this patient. Surprisingly, treatment with low-dose tacrolimus dramatically improved his HHT-associated epistaxis but did not attenuate progression of PAH.

  • Sommer, N.
  • Droege, F.
  • Gamen, K. E.
  • Geisthoff, U.
  • Gall, H.
  • Tello, K.
  • Richter, M. J.
  • Deubner, L. M.
  • Schmiedel, R.
  • Hecker, M.
  • Spiekerkoetter, E.
  • Wirsching, K.
  • Seeger, W.
  • Ghofrani, H. A.
  • Pullamsetti, S.

Keywords

  • ALK-1 mutation
  • Fk506
  • Morbus Osler
  • Vegf
  • tacrolimus
Publication details
DOI: 10.1177/2045894018805406
Journal: Pulm Circ
Pages: 2045894018805406 
Number: 2
Work Type: Original
Location: UGMLC
Disease Area: PH
Partner / Member: JLU, UMR
Access-Number: 30260738
See publication on PubMed

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