Interim Results of a Phase 1/2 Study of JR-171 (lepunafusp Alfa), a Novel Brain-Penetrant Enzyme Replacement Therapy for MPS I

To evaluate the effectiveness of artificial tears and corticosteroids on mitigating the acute ocular surface response to low-humidity environments.Single-group, crossover clinical trial.Twenty subjects with aqueous deficient dry eye were enrolled. Subjects meeting inclusion criteria at visit 1 were exposed to a baseline 90-minute low-humidity environment at visit 2. They then used artificial tears for 2 weeks prior to low-humidity exposure at visit 3, followed by 0.1% dexamethasone for 2 weeks prior to the final low-humidity exposure at visit 4. Outcome measures included corneal and conjunctival staining, blink rate, and irritation symptoms before and after each low-humidity exposure. Digital polymerase chain reaction (PCR) was performed to measure HLA-DR RNA transcripts in conjunctival cells taken by impression cytology at each visit.There was significantly less corneal and conjunctival epitheliopathy after the low-humidity exposure at visit 4 compared to after the low-humidity exposure at visit 3 (P = .003). Subjects reported significantly less eye irritation during the low-humidity exposure after using the dexamethasone (visit 4) compared to artificial tears (visit 3) (P = .01). HLA-DR transcripts significantly decreased after the stress at visit 4 (post dexamethasone) compared to visit 2.Our study demonstrates that corticosteroid eye drops mitigate the acute adverse effects of an experimental low-humidity challenge, likely owing to suppression of stress-activated inflammatory pathways. While extended use of corticosteroids is not indicated, other anti-inflammatory therapies with activity against stress-activated pathways may prove as effective.