Tivanisiran, a novel siRNA for the treatment of dry eye disease

Abstract

Dry eye disease (DED) is characterized by an alteration of the tear film with ocular inflammation and neurosensory abnormalities. The main clinical signs of this condition are tear instability and ocular damage. Although DED has gained significant attention in the past few years, limited prescription treatment options are available for patients. Areas covered: The current manuscript summarizes the pre-clinical and clinical development of tivanisiran, a novel small interfering oligonucleotide of RNA (siRNA) used for the treatment of DED. Tivanisiran was designed to silence Transient Receptor Potential Vanilloid 1 (TRPV1); herein the chemistry and mechanism of action of this new compound is also described. Expert opinion: Drugs currently on the market mostly target the inflammatory component of the disease and show only partial efficacy. New compounds addressing other aspects of the disease would provide significant advantages and contribute to a more personalized treatment of the disease. Tivanisiran has been designed to reduce ocular discomfort and pain, and was shown to improve ocular hyperemia and tear quality in human and animal models. Consequently, if the results of the ongoing and future clinical trials meet their study endpoints, tivanisiran could be submitted to obtain approval for the treatment of DED.

USP10 Targeted Self-Deliverable siRNA to Prevent Scarring in the Cornea

“…77 As may be expected, dosing the eye does not induce significant systemic effects. 44,[78][79][80][81] Many RNAi-based therapies are in various stages of clinical trials for multiple indications, with the use of modified siRNA conjugates becoming a dominant therapeutic modality. 82 Other RNAi-based therapies for hepatitis C and various cancers are also in clinical trials.…”

Epigenetic regulation of anterior segment diseases and potential therapeutics

“…Epigenetic therapy targets specific regulatory mechanisms, which minimizes the risk of complications that can be seen with systemic agents. Therapeutic targets have already been identified, including altered DNA methylation in Behcet's disease 91 and retinoblastoma 92 , histone modification in uveitis 59 and lens and conjunctival fibrosis 39,88 , and siRNA expression in dry eye disease 87 . Though this next generation of therapeutics holds significant promise for the future of medicine, challenges such as bioavailability and targeted drug delivery are still being addressed.…”

Biomarcadores en película lagrimal y su aplicación clínica.

“…Biomarcadores en película lagrimal y su aplicación clínica Durán S recientemente se ha informado el desarrollo preclínico y clínico de pequeños ARN interferentes que inducen una represión en genes que favorecen el desarrollo del ojo seco como lo es el receptor del potencial transitorio V1 implicado en la inflamación y en la respuesta somatosensorial de la superficie ocular (54).…”