Treatment of fibrosis with ALDH inhibitors
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Fibrosis is the formation of excess fibrous connective tissue in response to injury and inflammation. If it happens in response to injury it is also referred to as scarring. Fibrosis is associated with conditions such as cystic fibrosis, cirrhosis, mucous membrane pemphigoid (MMP), pulmonary fibrosis and scleroderma. It is also a consequence of surgery, and especially causes problems after ocular surgery and is a common cosmetic problem. Researchers at UCL Institute of Ophthalmology have found that alcohol dehydrogenase inhibitors can be used in the treatment and prevention of fibrosis.
The Technology and its Advantages
Researchers at UCL Institute of Ophthalmology have found that aldehyde dehydrogenase 1 family member A3 (ALDH1A3) is a new molecular player in the fibrosis pathway in ocular scaring which is upregulated in Ocular MMP (OcMMP) and can be targeted with aldehyde dehydrogenase inhibitors. Aldehyde dehydrogenases are a group of enzymes catalysing dehydrogenation of aldehyde to carboxylic acid. One of the most commonly available dehydrogenase inhibitors is disulfiram – a compound used in the treatment of alcohol dependency. In alcoholism it is used systematically, where it disrupts the metabolism of alcohol causing unpleasant reaction upon consumption of alcohol. Topical use of disulfiram would prove more applicable, permitting fibrosis patients to consume alcohol and would make it available for patients with myocardial disease, coronary occlusion, who cannot take it systemically. These findings pave the way for the use of dehydrogenase inhibitors as topical agents in treatment and prevention of fibrosis in a wide range of conditions and as a cosmetic agent.
MMP is an orphan indication. Currently used immunosuppressive and anti-inflammatory approaches are not effective. The average age of onset of MMP is 60-70 years and it is more common in women than in men causing discomfort and blindness in 30% of cases. The current treatment for MMP takes 6-16 weeks to become effective and fails to arrest the scarring. Beyond the treatment of MMP, ALDH can be used against scarring associated with glaucoma filtration surgery and other surgical procedures performed on the eye. Outside of the ophthalmology arena, scarring therapies and cosmetic solutions are a large unmet need.
Intellectual Property Status
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The technology referred to herein is experimental in nature and UCL Business PLC makes no representations and gives no warranties of any kind, either express or implied, in relation to the technology and, in particular but without limiting the foregoing, UCL Business PLC gives no express or implied warranties of merchantability, satisfactory quality or fitness for a particular purpose.