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GS-101 is an experimental, topical therapy for the treatment of Neovascularisation associated with CGR and is an antisense oligonucleotides (single stranded DNA fragment)
An avascular recipient cornea is commonly regarded as an important prognostic factor for long-term survival of a corneal graft.1 Cornea avascularity is essential not only for corneal transparency and vision, but also for granting immune-privilege to the cornea to protect the donor cornea from being rejected.2
Corneal graft rejection is primarily a cell-mediated immune response controlled by T cells.3 Normal corneal immune privilege can be eroded by neovascularisation, especially if accompanied by the sequelae of ocular inflammation and raised intraocular pressure. This is because if neovascularisation is present either before or after a corneal graft, the growth of new blood vessels (angiogenesis) provides a route of entry for immune-mediating cells to the graft, while the growth of new lymphatic vessels enables the exit of APCs and antigenic material from the graft to regional lymph nodes. The cornea consequently becomes infiltrated with and sensitized to immune reaction mediators (i.e. APCs, T cells, macrophages, neutrophils). Therefore, although not an immune reaction in itself neovascularisation induces an immune response that can lead to immunological corneal graft rejection.4,5
GS-101 is an antisense oligonucleotide administered in the form of eye drops. It acts by blocking the production of the IRS-1, a protein required for the formation and growth of new blood vessels. By blocking the expression of IRS-1 in pro-angiogenic conditions, GS-101 inhibits and regresses corneal neovascularisation. It is well documented that the risk of a corneal graft rejection rises by two-thirds from a vascular eye to a highly neovascularised one.6
GS101 is currently entering Phase III clinical trials for the management of neovascularisation in Corneal indications, having successfully completed Phase I and now closing Phase II.
In April 2007, the EMEA granted Gene Signal orphan designation for GS-101 for the prevention of Corneal Graft Rejection. Orphan designation is granted by many regulatory agencies in order to promote the development of therapies for rare diseases.
