Yesterday, Clinuvel announced the grant of a new patent from the USPTO – allowing the company exclusive protection for the use of afamelanotide (SCENESSE®) and any molecule belonging to the family of melanocortins for UV-protection of individuals who are at high risk of skin cancers. This patent, granting protection until 2024, refers specifically to individuals with defects (allelic variations) seen in the melanocortin-1 receptor (MC1R). The MC1R plays a key role in the pigmentary response and defensive mechanism to UV.
The MC1R is vital in regulating the quantity of melanin in skin and an individual’s pigmentary response; one’s ability to activate the protective dark pigment eumelanin in skin after UV induced skin damage (also known as the ‘tanning response’ after erythema).Allelic variations of the MC1R – of which there are over 80 identified in medical literature – are considered highly prevalent in fair skinned populations of European descent, with reports of up to 75% prevalence in Ireland. In red haired coloured (RHC) individuals single or multiple variations are seen in 93% of people tested. Conversely, variations are not seen in African populations, rather a wild type MC1R is referred to in those with darker skin.
The defects in the MC1R give rise to increase in the risk of skin cancer in affected individuals whereby two mechanisms occur. Firstly, partial or total loss of function of the MC1R can occur, resulting in the inadequate UV response and increased skin damage. The lack of eumelanin is said to be the contributing factor in fair-skinned individuals to photodamage and increased carcinogenic risk. Eumelanin is known to provide protection to skin from light and UV (photoprotection). By absorbing, reflecting and refracting light, melanin prevents photons (light particles) from penetrating the skin and causing cellular damage.
Secondly, loss of function of the MC1R can compromise the cellular (melanocyte and keratinocyte) machinery by which skin responds to damage caused by UV radiation; specifically the cells’ innate ability to repair DNA damage by eliminating photoproducts. Nucleotide excision repair (NER) is one such mechanism which is in place following UV damage under physiological conditions, and compromised in fair-skinned individuals.
Four MC1R variations in particular – R142H, R151C, R160W and D294H, those most commonly associated with red hair, fair skin and reduced ability to tan – are commonly seen in patients with melanoma skin cancer and, together with a history of sunburn, are reported to double the risk of lifetime melanoma.
To sum it up, with a reduced ability to both protect from, and respond to, invasive UV radiation, individuals with MC1R variations are considered to be at significantly higher risk of skin cancers.
For Clinuvel, the US patent provides the company unique protection in the field of photoprotection, covering a scope of SCENESSE® and family of alpha-MSH analogues as photoprotective agents.
Further reading:
- Causes of skin cancer on Clinuvel Skin & Health
- UV damage and carcinogenesis on Clinuvel Skin & Health
- The physiological “UV tanning response”, original thoughts on UV and pigmentation, Technology update from Clinuvel
References:
Abdel-Malek ZA, Kadekaro AL, Swope VB. (2010). “Stepping up melanocytes to the challenge of UV exposure.” Pigment Cell Melanoma Res. 23(2):171-86. Epub 2010 Feb 1. Abstract
García-Borrón JC, Sánchez-Laorden BL, Jiménez-Cervantes C. (2005). “Melanocortin-1 receptor structure and functional regulation.” Pigment Cell Res. 18(6):393-410. Review. Abstract
Rouzaud F., Kadekero A.L., Abdel-Malek Z.A., Hearing V.J. (2005). “MC1R and the response of melanocytes to ultraviolet radiation”. Mutation Research. 571: 133-152. Abstract
Image reference:
http://www.flickr.com/photos/derekgavey/
