Sylentis Presents New Data On Its Compounds For The Treatment Of Glaucomas And Dry Eye Syndrome At ARVO Congress

Main Category: Eye Health / Blindness
Article Date: 21 May 2009 - 4:00 PDT

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Sylentis, a bio-pharmaceutical company Zeltia Group (MC: ZEL), a pioneer in research and development of new drugs based on gene silencing technology of RNA interference (RNAi), has presented new data on their compounds for ophthalmic indications at the Congress of the Association for Research in Vision and Ophthalmology (ARVO), held from May 3-7, 2009 in Fort Lauderdale, Florida.

Founded in 2006, a company of the Zeltia Group and spin-off of Genomica SA (a biotech company of the Zeltia Group) is a reference company in new therapies based on RNAi technology. Sylentis is devoted to the design of efficient siRNA's through its technology: SIRFINDER®, which allows to obtain small fragments of RNAi (siRNA - short interfering RNAs) with pharmacological potential through a search of the most appropriate sequences using bioinformatic techniques; once the target gene involved in a disease is identified, Sylentis designs siRNA targeting this gene in a short period of time and with a reduced cost.

During ARVO congress, Sylentis has provided an update on recent advances made by the company in the development of its portfolio of compounds against ophthalmic diseases, with the presentation of two posters on new data of their compounds for the treatment of ocular pain associated with dry eye syndrome and open-angle glaucoma.

Sylentis is developing a product for ocular pain associated with dry eye syndrome that addresses TRPV1 receptor, a nociceptor able to transmit stimuli. Two studies were presented in the poster "A New Treatment for Ocular Pain Associated To Dry Eye Syndrome Based On RNAi Technology: In Vivo Results" that concluded that two siRNA formulations directed against trpv1, have shown greater analgesic effect than the reference standard Capsazepina (reference analgesic) at the tested doses. A dose response study with SYL054003 showed that the effect did not follow a classic linear dose response.

TRPV1 channels are ocular nociceptors that mediate inflammation and pain. It is possible that reduced levels of expression of these nociceptors cause attenuated behaviour response to corneal irritation by the irritant capsaicin. Thus, the silencing of TRPV1 by administration of siRNA can be a useful therapy in the treatment of ocular pain associated with dry eye syndrome. Decrease of TRPV1 through a topically administered RNAi can reduce ocular pain in a highly specific way, which could reduce side effects associated with medications currently used to treat patients suffering from this pathology.

The study under the title "Efficacy of Topically Administered siRNA in Glaucoma Treatment: In vivo Results in hypertensive Model" was designed to demonstrate in vivo efficacy of topically administered siRNAs for the treatment of ocular hypertension associated to open angle glaucoma. Conclusions were that the model of transient hypertension induced by water-loading is a good model to evaluate effectiveness of different anti-glaucoma drugs, since it does alter the various ocular structures.

It was demonstrated in these studies that pre-treatment with SYL040003 and SYL040003 respectively prevents IOP increase induced by this ocular hypertension model. The prophylactic effect of these compounds is higher than the previously described effect in this model for drugs currently used for the treatment of glaucoma, such as Timolol and Xalatan.

RNA interference (RNAi)

In the last years, RNA interference (RNAi) has begun to emerge as a promising technology to be applied to therapeutics. This phenomenon, discovered in plants in the early 1990s, consists of a 3 specific and selective inhibition of gene expression in an extremely efficient manner (Fire et al., 1998). RNAi is mediated by small interfering RNA, consisting of 19-23 nucleotide double-stranded RNA duplex, that promote specific endonucleolytic cleavage of mRNA targets through an RNAinduced silencing complex. RNAi holds great therapeutic promise for gene silencing, as siRNA is naturally used by cells to regulate gene expression in a nontoxic and highly effective way.

Primary open-angle glaucoma (POAG)

Primary open-angle glaucoma (POAG) is the most common form of glaucoma throughout the world accounting for about two-thirds of cases. It is defined as a multifactorial optic neuropathy in which there is a characteristic acquired loss of retinal ganglion cells and athropy of the optic nerve causing progressive and irreversible blindness. Risk factors for the development of POAG include elevated intraocular pressure (IOP), family history of the disease and advanced age (Marquis and Witson, 2005). Although the pathophysiological mechanisms by which elevated pressure leads to neuronal damage in glaucoma are unknown, most of current therapies include medications or surgeries aimed at lowering IOP to a level which safely halts progressive visual loss.

Ocular Pain associated to Dry Eye Syndrome

Ocular pain may be described as a burning, throbbing, aching, or stabbing sensation in or around the eye. It may also feel as if there is a foreign body in the eye. Chronic ocular pain is usually associated to ocular pathologies such us Dry Eye Syndrome. Decreasing this symptom is essential to improve the patients´ quality of life. Nowadays, there is no approved medication to specifically reduce chronic ocular pain.

Source
Sylentis

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