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Does Patisiran Reduce Ocular Transthyretin Synthesis? A Pilot Study of Two Cases
Chiara Cambieri1, Marco Marenco2, Tania Colasanti3
1Department of Human Neuroscience, Centre for Rare Neuromuscular Disease, Sapienza University of Rome, Rome, Italy.
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.
