One of the key strategic aims of the Dermatology and Genetic Medicine group is to translate our discoveries in genetics into new improved treatments for patients. In close collaboration with the Drug Discovery Unit, we have been pursuing a number of small molecule drug discovery projects aimed at treatment of genetic disorders, particularly those affecting the skin.
One of our projects is aimed at drug repurposing, where we look for new uses of known drugs to treat rare, neglected diseases. One of our target diseases is the rare keratinizing skin disorder pachyonychia congenita (PC), which is caused by mutations in any one of the genes encoding keratins K6a, K6b, K6c, K16 or K17. Another is the hereditary skin blistering disorder epidermolysis bullosa simplex (EBS), which is mostly caused by mutations in either one of the keratin K5 or K14 genes.
Secondly, we have developed novel chemical compounds that may be able to benefit patients with a particular class of genetic mutations (nonsense mutations) that leads to an important gene being essentially “switched off”. We have identified classes of small molecules that can “fool” human cells into ignoring nonsense mutations and thereby resurrecting the faulty, inactive gene. If successful, this project could be beneficial to many hundreds of genetic diseases where the causative defect is a nonsense mutation in an essential gene.
- Lane EB and McLean WHI (2008). Broken bricks and cracked mortar – epidermal diseases resulting from genetic abnormalities. Drug Discov Today: Disease Mechanisms, 5: 393-401.
- Zhao Y et al., (2011) Statins downregulate K6a promoter activity: a possible therapeutic avenue for pachyonychia congenita. J Invest Dermatol. 131: 1045-1052 (PubMed ID: 21390048)