Does Patisiran Reduce Ocular Transthyretin Synthesis? A Pilot Study of Two Cases

• Published in: Current neuropharmacology Vol. 21; no. 12; pp. 2543 - 2549
• Main Authors: Cambieri, Chiara, Marenco, Marco, Colasanti, Tania, Mancone, Carmine, Corsi, Alessandro, Riminucci, Mara, Libonati, Laura, Moret, Federica, Chimenti, Cristina, Lambiase, Alessandro, Conti, Fabrizio, Garibaldi, Matteo, Inghilleri, Maurizio, Ceccanti, Marco
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers 01-01-2023
• Subjects: Cataract - drug therapy; Glaucoma - drug therapy; Humans; Medicine, Neurology, Pharmacology, Neuroscience; Pilot Projects; Prealbumin; RNA interference; transthyretin; ATTR-v; Amyloidosis; siRNA; patisiran; ATTR; ocular
• ISSN: 1570-159X; 1875-6190
• DOI: 10.2174/1570159X21666230623094710

Background: Variant transthyretin-mediated amyloidosis (ATTR-v) is a well-characterized disease affecting the neurologic and cardiovascular systems. Patisiran has been approved for neurologic involvement as it reduces hepatic synthesis of transthyretin (TTR). Eye involvement is a lateonset feature increasing the risk of glaucoma and cataracts in patients. Aims: The aim of this case series was to assess whether patisiran can effectively reduce TTR synthesis in such a barrier-protected organ as the eye. Methods: Two patisiran-treated ATTR-v patients underwent serum and aqueous humor sampling to measure TTR levels detected by SDS-PAGE and immunoblotting. Serum samples were compared to healthy control (HC), whereas aqueous humor samples were compared to non-amyloidotic subjects affected by cataracts and glaucoma. Results: Serum TTR levels representative of hepatic synthesis were sharply lower in treated patients if compared to the HC (-87.5% and -93.75%, respectively). Aqueous humor TTR levels showed mild-tono reduction in treated patients compared to non-amyloidotic subjects with cataracts (-34.9% and +8.1%, respectively) and glaucoma (-41.1% and -2.1%). Conclusion: Patisiran does not seem to be as effective in inhibiting ocular TTR synthesis as it is in inhibiting hepatic synthesis. Re-engineering the envelope could allow the drug to target RPE cells thus avoiding any ocular involvement.