Observational Study

. 2025 Feb 15;272(3):209.

doi: 10.1007/s00415-025-12950-3.

Patisiran in ATTRv amyloidosis with polyneuropathy: "PatisiranItaly" multicenter observational study

Vincenzo Di Stefano¹, Pietro Guaraldi², Angela Romano³, Giovanni Antonini⁴, Alessandro Barilaro⁵, Chiara Briani⁶, Marco Burattini⁷, Ilaria Cani², Giulia Carlini⁸, Marco Ceccanti⁹, Vittoria Cianci¹⁰, Pietro Cortelli², Marco Currò Dossi¹¹, Daniela Di Lisi¹², Antonio Di Muzio¹³, Yuri Falzone¹⁴, Massimiliano Filosto^{15

16}, Sabrina Gasverde¹⁷, Chiara Gemelli¹⁸, Luca Gentile¹⁹, Mariangela Goglia²⁰, Luca Leonardi²¹, Simone Longhi²², Antonio Lotti⁵, Fiore Manganelli²³, Anna Mazzeo¹⁹, Giammarco Milella²⁴, Giuseppina Novo¹², Silvia Fenu²⁵, Giovanni Palumbo²³, Cristina Petrelli²⁶, Loris Poli²⁷, Luca Guglielmo Pradotto^{28

29}, Massimo Russo¹⁹, Alessandro Salvalaggio⁶, Maria Ausilia Sciarrone³⁰, Luigi Sellitti²⁹, Matteo Tagliapietra³¹, Stefano Tozza²³, Mara Turri³², Lorenzo Verriello³³, Francesca Vitali³⁰, Filippo Brighina^#¹, Marco Luigetti^#^{34

35}

Affiliations

¹ Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, Palermo, Italy.
² IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
³ Dipartimento di Neuroscienze, Organi di Senso e Torace, UOC Neurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.
⁴ Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, 'Sapienza' University of Rome and UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy.
⁵ AOU Careggi and Department of Neurosciences, Drug and Child Health, University of Florence, Florence, Italy.
⁶ Neurology Unit, Department of Neuroscience, University of Padua, Padua, Italy.
⁷ Neurology Unit, Ospedale Santa Croce di Fano, Fano, Italy.
⁸ Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
⁹ Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
¹⁰ Neurology Unit, Great Metropolitan Hospital "Bianchi Melacrino Morelli", Reggio Calabria, Italy.
¹¹ Department of Neurology, Infermi Hospital, Rimini, Italy.
¹² Division of Cardiology, University Hospital Paolo Giaccone, Palermo, Italy.
¹³ Department of Neuroscience, Imaging and Clinical Sciences, "G. D'Annunzio" University, Chieti, Italy.
¹⁴ Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
¹⁵ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
¹⁶ NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy.
¹⁷ ASL TO4, Ciriè, Italy.
¹⁸ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁹ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
²⁰ Neuromuscular Diseases Unit, Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy.
²¹ Neuromuscular and Rare Disease Centre, Neurology Unit, Sant'Andrea Hospital, Rome, Italy.
²² Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
²³ Department of Neuroscience, Reproductive and Odontostomatological Science, University of Naples 'Federico II', Naples, Italy.
²⁴ Neurology Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
²⁵ S.C. Malattie Neurologiche Rare, Dipartimento di Neuroscienze Cliniche, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²⁶ Neurology Unit, AV3, ASUR Marche, Macerata, Italy.
²⁷ Unit of Neurology, ASST Spedali Civili, 25100, Brescia, Italy.
²⁸ Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
²⁹ IRCCS Istituto Auxologico Italiano, Piancavallo (Vb), Milan, Italy.
³⁰ Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
³¹ Department of Neuroscience, Biomedicina e Movimento, Università di Verona, Verona, Italy.
³² Dipartimento di Neurologia/Stroke Unit, Ospedale di Bolzano, Bolzano, Italy.
³³ Neurology Unit, Department of Neurosciences, University Hospital Santa Maria della Misericordia, Udine, Italy.
³⁴ Dipartimento di Neuroscienze, Organi di Senso e Torace, UOC Neurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy. mluigetti@gmail.com.
³⁵ Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy. mluigetti@gmail.com.

^# Contributed equally.

PMID: 39954098
PMCID: PMC11829936
DOI: 10.1007/s00415-025-12950-3

Observational Study

Patisiran in ATTRv amyloidosis with polyneuropathy: "PatisiranItaly" multicenter observational study

Vincenzo Di Stefano et al. J Neurol. 2025.

. 2025 Feb 15;272(3):209.

doi: 10.1007/s00415-025-12950-3.

Authors

Affiliations

¹ Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, Palermo, Italy.
² IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
³ Dipartimento di Neuroscienze, Organi di Senso e Torace, UOC Neurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy.
⁴ Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, 'Sapienza' University of Rome and UniCamillus-Saint Camillus International University of Health Sciences, Rome, Italy.
⁵ AOU Careggi and Department of Neurosciences, Drug and Child Health, University of Florence, Florence, Italy.
⁶ Neurology Unit, Department of Neuroscience, University of Padua, Padua, Italy.
⁷ Neurology Unit, Ospedale Santa Croce di Fano, Fano, Italy.
⁸ Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
⁹ Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
¹⁰ Neurology Unit, Great Metropolitan Hospital "Bianchi Melacrino Morelli", Reggio Calabria, Italy.
¹¹ Department of Neurology, Infermi Hospital, Rimini, Italy.
¹² Division of Cardiology, University Hospital Paolo Giaccone, Palermo, Italy.
¹³ Department of Neuroscience, Imaging and Clinical Sciences, "G. D'Annunzio" University, Chieti, Italy.
¹⁴ Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
¹⁵ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
¹⁶ NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy.
¹⁷ ASL TO4, Ciriè, Italy.
¹⁸ IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁹ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
²⁰ Neuromuscular Diseases Unit, Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy.
²¹ Neuromuscular and Rare Disease Centre, Neurology Unit, Sant'Andrea Hospital, Rome, Italy.
²² Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
²³ Department of Neuroscience, Reproductive and Odontostomatological Science, University of Naples 'Federico II', Naples, Italy.
²⁴ Neurology Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
²⁵ S.C. Malattie Neurologiche Rare, Dipartimento di Neuroscienze Cliniche, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²⁶ Neurology Unit, AV3, ASUR Marche, Macerata, Italy.
²⁷ Unit of Neurology, ASST Spedali Civili, 25100, Brescia, Italy.
²⁸ Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy.
²⁹ IRCCS Istituto Auxologico Italiano, Piancavallo (Vb), Milan, Italy.
³⁰ Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
³¹ Department of Neuroscience, Biomedicina e Movimento, Università di Verona, Verona, Italy.
³² Dipartimento di Neurologia/Stroke Unit, Ospedale di Bolzano, Bolzano, Italy.
³³ Neurology Unit, Department of Neurosciences, University Hospital Santa Maria della Misericordia, Udine, Italy.
³⁴ Dipartimento di Neuroscienze, Organi di Senso e Torace, UOC Neurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168, Rome, Italy. mluigetti@gmail.com.
³⁵ Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy. mluigetti@gmail.com.

^# Contributed equally.

PMID: 39954098
PMCID: PMC11829936
DOI: 10.1007/s00415-025-12950-3

Abstract

Background: Hereditary amyloid transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare, inherited, multisystemic, progressive adult-onset disease, affecting sensorimotor nerves, and various organs. It is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate, forming amyloid fibrils. Patisiran is a small, double-stranded interfering RNA encapsulated in a lipid nanoparticle, designed to enter hepatocytes and selectively target TTR mRNA to reduce both variant TTR and wild-type TTR (wt). This study presents a multicenter, real-life experience of patisiran's effectiveness and safety in ATTRv-PN.

Methods: We enrolled genetically confirmed ATTRv-PN patients from 29 specialized Italian centers. All subjects underwent neurological assessments, including familial amyloid polyneuropathy (FAP) staging, the Neuropathy Impairment Score (NIS), quality-of-life assessment using the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire, and the Compound Autonomic Dysfunction Test (CADT). Additional assessments included baseline and follow-up measures of serum NT-proBNP and interventricular septal thickness.

Results: A total of 181 ATTRv patients (69% male) were enrolled. Neurological onset was reported in 60.2% of cases. At baseline, 83.4% of patients exhibited multisystemic involvement, while only 16.6% presented isolated polyneuropathy. For approximately 70% of patients, patisiran was the first treatment; the remainder transitioned from tafamidis or inotersen. Following treatment, most patients demonstrated stabilization of neuropathy progression, regardless of baseline disease severity or genotype. The treatment was well-tolerated, with 90% of patients reporting no adverse events.

Conclusion: Patisiran can be considered a valid therapeutic option for the management of patients with ATTRv amyloidosis. Considering its mechanism of action, similar outcomes could also be expected with the wider utilization of newly approved gene silencers for ATTRv therapy, such as vutrisiran.

Keywords: ATTRv-PN; Hereditary transthyretin amyloidosis; Multicenter study; Patisiran; RNA interference; Real-world data.

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Conflict of interest statement

Declarations. Conflicts of interest: A.R. received financial grants (honoraria and speaking) from Akcea, and travel grants to attend scientific meetings from Akcea, Alnylam, Pfizer, and Csl Behring. A.B. received financial grants (honoraria and speaking) from Alnylam. C.B. received speaker and consulting honoraria from Alnylam, Ionis, and Pfizer, and travel grants from Kedrion, Alnylam, and CSL Behring. S.F. acknowledges financial support from Alnylam and Pfizer for participation in national and international meetings. C.G. received financial grants (speaking) from Italfarmaco, and travel grants from Biogen for participation in national meetings. L.G. received financial grants (honoraria and speaking) from Akcea, Alnylam, and Pfizer, and travel grants from Alnylam and CSL Behring. L.L received financial grants (honoraria and speaking) from Alnylam, and travel grants to attend scientific meetings from Akcea, SOBI, Alnylam. A.S. received a travel grant to attend scientific meetings from Alnylam. S.T. received personal fees for scientific events from Alnylam Pharmaceuticals, Amicus Therapeutics and Takeda Pharmaceutical Co, travel grants to attend scientific meetings from Akcea Therapeutics. M.L. received financial grants (honoraria and speaking) from Ackea, Alnylam, Sobi, and Pfizer, and travel grants from Ackea, Alnylam, Sobi, Pfizer, Kedrion, and Grifols. Other authors have no conflict of interest to declare. Ethical approval and consent to participate: The study was approved by the Ethical Committee of Palermo on 26th June 2023 (V n.6/2023), and it was conducted in conformity with the Declaration of Helsinki principles. Written informed consent was obtained from each enrolled individual before inclusion.

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Patisiran in ATTRv amyloidosis with polyneuropathy: "PatisiranItaly" multicenter observational study

Affiliations

Patisiran in ATTRv amyloidosis with polyneuropathy: "PatisiranItaly" multicenter observational study

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