Orly Moshe-Lilie1, Diana Dimitrova1, Stephen B Heitner2, Thomas H Brannagan3, Sasha Zivkovic4, Mazen Hanna5, Ahmad Masri2, Michael Polydefkis6, John L Berk7, Morie A Gertz8, Chafic Karam1. 1. Department of Neurology, Oregon Health & Science University, Portland, OR, USA. 2. Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, OR, USA. 3. Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. 4. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA. 5. Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA. 6. Department of Neurology, John Hopkins Medicine Institute, Baltimore, MD, USA. 7. Department of Medicine, Boston University Medical Center, Boston, MA, USA. 8. Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Abstract
Objective: Patients with hereditary transthyretin (TTR) amyloidosis (hATTR) often experience disease progression after orthotopic liver transplant (POLT) due in part to wild type ATTR amyloid deposition. The management strategy is not defined. We propose that TTR gene silencing with an antisense oligonucleotide or a small interfering ribonucleic acid may be a treatment for these patients. Methods: We reviewed the charts of hATTR patients POLT treated with a TTR gene silencing agent at 7 different Amyloid Clinics between 2018-2020. Results: Nine hATTR patients with POLT were treated with TTR gene silencing therapy (Inotersen). The median age was 61 years. The median time from OLT to initiation of TTR gene silencing therapy was 7.5 years. The median duration of therapy was 12 months. Neuropathy impairment score remained stable or improved in all patients. Five patients stopped treatment: 3 because of thrombocytopenia, 2 because of reversible liver rejection. Three patients who discontinued treatment subsequently experienced worsening of their neuropathy. Conclusion: TTR gene silencing therapy in hATTR patients with POLT could be a treatment option. Vigilant monitoring of renal, liver and bone marrow functions is necessary because of frequent complications. Further studies are needed to determine efficacy.
Objective: Patients with hereditary transthyretin (TTR) amyloidosis (hATTR) often experience disease progression after orthotopic liver transplant (POLT) due in part to wild type ATTR amyloid deposition. The management strategy is not defined. We propose that TTR gene silencing with an antisense oligonucleotide or a small interfering ribonucleic acid may be a treatment for these patients. Methods: We reviewed the charts of hATTRpatients POLT treated with a TTR gene silencing agent at 7 different Amyloid Clinics between 2018-2020. Results: Nine hATTRpatients with POLT were treated with TTR gene silencing therapy (Inotersen). The median age was 61 years. The median time from OLT to initiation of TTR gene silencing therapy was 7.5 years. The median duration of therapy was 12 months. Neuropathy impairment score remained stable or improved in all patients. Five patients stopped treatment: 3 because of thrombocytopenia, 2 because of reversible liver rejection. Three patients who discontinued treatment subsequently experienced worsening of their neuropathy. Conclusion:TTR gene silencing therapy in hATTRpatients with POLT could be a treatment option. Vigilant monitoring of renal, liver and bone marrow functions is necessary because of frequent complications. Further studies are needed to determine efficacy.
Authors: Velina Nedkova-Hristova; Carmen Baliellas; José González-Costello; Laura Lladó; Emma González-Vilatarsana; Valentina Vélez-Santamaría; Carlos Casasnovas Journal: Transpl Int Date: 2022-04-13 Impact factor: 3.842
Authors: Hartmut H Schmidt; Jonas Wixner; Violaine Planté-Bordeneuve; Francisco Muñoz-Beamud; Laura Lladó; Julian D Gillmore; Anna Mazzeo; Xingyu Li; Seth Arum; Patrick Y Jay; David Adams Journal: Am J Transplant Date: 2022-03-26 Impact factor: 9.369