Corneal scarring - lerdelimumab
Glaucoma is a serious eye condition, in which very high pressure within the eye ultimately results in loss of vision. Its incidence increases with age. Chronic simple, or open angle, glaucoma is the most common form, and is characterised by a gradual, generally painless, rise in pressure, and visual impairment progresses slowly.
Acute, or angle closure, glaucoma involves a rapid rise in intraocular pressure, is less common. It is caused by the sudden closing of the angle between the cornea and the iris, blocking the drainage of aqueous humour from the eye. Pain and visual blurring result.
Drug therapy is the first option for treatment. Acetazolamide, for example, stops aqueous humour being produced, while other drugs improve the drainage of intraocular fluid. If these are not successful, then surgery or laser treatment becomes necessary. However, these all too often cause post-operative scarring as a result of excess amounts of trans-forming growth factor b (TGFb), and this can cause the surgery to fail.
Drugs such as 5-fluorouracil or mitomycin C, more commonly used in cancer therapy, are often used to prevent scarring, but the apoptosis they induce can all too often lead to blindness. An alternative would be to prevent the formation of TGF-b2, the form concentrated in the eye, and Cambridge Antibody Technology has created a recombinant human monoclonal antibody for this purpose.
The antibody, lerdelimumab, formerly referred to as CAT-152, was given in doses of 100µg to 16 patients undergoing surgery for glaucoma, and placebo to a further eight.1 It was administered in four doses as subconjunctival injections just before, just after, and again a day and a week afterwards. Intraocular pressure was reduced in both groups, but was significantly lower, even after a year, in those given the antibody. They also required fewer further clinical interventions afterwards.
In a further placebo-controlled trial in 56 patients, subjects were given four 100µg doses of lerdelimumab or placebo as subconjunctival injections, again just before, just after, a day after and a week after surgery.2 Fewer problems were seen after six months in the group given the active, and intraocular pressure was again lower in the treated group.
Phase II/III trials are under way, and if successful lerdelimumab could greatly improve the outcome of surgery in glaucoma patients.