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Victoria Gonzalez, Ana Isabel Jímenez, Tamara Martínez; SYL1001 Targeting TRPV1 Receptor for the Treatment of Ocular Pain associated to Dry Eye Syndrome. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3844.
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To develop a new treatment for ocular pain and ocular discomfort associated to dry eye syndrome based on topically administered siRNA targeting TRPV1 expression on the ocular surface. Efficacy results are presented in a rabbit model of ocular irritation induced by application of the natural agonist of TRPV1, capsaicin. Toxicology evaluation was carried out in two non-rodent species following FDA/EMA guidelines
Different siRNA sequences targeting TRPV1 gene, previously validated by in vitro assays, were tested in vivo in the New Zealand white rabbit to analyze the effect in blocking the irritant effect on ocular surface induced by capsaicin. SYL1001 was selected as the best candidate for TRPV1 receptor. Palpebral opening was measured and conjunctival hyperemia and animal behaviour was evaluated. Results were compared to those obtained with animals treated with the reference analgesic capsacepine. SYL1001 toxicology and pharmacokinetic evaluation were carried out in Dogs and Rabbits.
In vitro and in vivo studies successfully demonstrated that ocular topical administration of SYL1001 was able to reduce TRPV1 levels and ocular pain in New Zealand white rabbits. Moreover, topical administration of SYL1001 prevents ocular pain after pain induction by capsaicin with a similar or higher analgesic effect than the reference analgesic standard. The toxicology experiments performed with SYL1001 by ocular topical route to dogs and rabbits indicated that no side effects were observed during 28-days of treatment. Pharmacokinetic analysis showed that no drug was detected above the detection limit (40 ng/mL) at any time or dose tested.
SYL1001 specifically directed to silence the TRPV1 gene appears to decrease the behavioural response to ocular surface irritation evoked by ocular capsaicin. These channels are involved in the nerve impulse responses to exogenous and endogenous substances mediating inflammation and pain. Toxicology results indicated that SYL1001 did not produce any adverse events related to treatment. SYL1001 has been demonstrated to be safe and efficient in recommended animal models, which suggest this product could be a very good candidate for treatment of ocular pain.
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