Actinic Keratosis (or Solar Keratosis)
Approximately 50% of the world's population have problems with AK's. In the US, consultations for AK's are the second most common reason for patient visits to dermatologists and treatment of these lesions has become a major part of dermatology practice. The prevalence of AK's varies geographically with the incidence amongst Australians 40 years of age or older reported to be 40-60% compared with approximately 10-20% of the population in Europe and the US.
The major clinical consequences of AK's are that these lesions may transition into skin cancer. It is not expected that afamelanotide (CUV1647) will totally eliminate the effects of previous long term exposure to UVR but that it will reduce, eliminate or mitigate the effects of future continued exposure. This will be the second major indication to be developed for CUV1647. Phase II trials began in November 2007.
A subset of this program will be a study to determine the effects of afamelanotide (CUV1647) in immune-compromised individuals. These subjects will be chosen from a population of organ transplant patients who are particularly prone to develop AK's and skin cancer after only minimal exposure to UVR.
Afamelanotide's ability to regulate melanin production and release may be utilised to assist in alleviating UV-related skin disorders which are exacerbated by UVR.
Current literature shows evidence that subjects without protective eumelanin (pigmentation) are far more susceptible to skin cancer (squamous cell carcinoma, basal cell carcinoma, melanoma) than are African Americans.
Epidemiological data indicates indeed that light from the ultra-violet spectrum (290 to 420 nanometres) through its mutagenic activity is the most likely cause of skin cancer in Caucasians (people with light coloured skin).
In the US, incidence rates of melanoma (pigmented malignancies of the skin) in white males amount to 25:100,000 compared to black males where the rate is much lower in 1.4:100,000. In comparison, for white females vs. black females the incidence rate is 17.9:100,000 vs. 1.1:100,000 (Tsai, et al. 2005).
Another illustration of the photo-protective properties of eumelanin is shown in a South African study where only 1.2:100,000 indigenous Africans suffered from malignant melanoma (Giraud, et al. 1975) while the rate of malignant melanoma for Caucasians living in Cape Town was found to be 24.4:100,000 (Hoffman et al., 1998). The rate of other prominent skin cancers (squamous cell carcinoma and basal cell carcinoma) in albinos (people with non-pigmented skin) belonging to the black indigenous population was found to be 23.4% (Kromberg et al., 1989). This equates to incidences of approximately 25% in white South Africans seen in dermatology practices over a span of 7 years (Whiting, 1978).
In a population based study in Australia, it was calculated that men with fair skin had a 6.2 times more chance of developing skin cancer in their lifetime than men with naturally high levels of melanin (Dwyer et al., 2002).
For more information on AK, please see the Clinuvel Photoprotection AK page.
References
1. Hadley, et al. The Proopiomelanocortin system. An. N.Y.
Acad. Sci. 1999, 885:1-21.
2. Tsai, et al. Cutaneous, ocular and visceral melanoma in African
Americans and Caucasians. Melanoma Res. 2005, 15:213-217.
3. Giraud, et al. Malignant melanoma of the skin in Black Africans.
S Afr Med J. 1975, 16:665-8.
4. Hoffman et al. Malignant melanoma in Cape Town, South Africa.
Br J Dermatol. 1998, 138:998-1002.
5. Kromberg et al. Albinism and skin cancer in Southern Africa.
Clin. Genet. 1989, 36:43-52.
6. Whiting. Skin tumours in White South Africans. Part I. Patients,
methods and incidence. S Afr Med J. 1978, 53:98-102.
7. Dwyer et al. Cutaneous Melanin Density of
Caucasians measured by spectrophotometry and risk of malignant
melanoma, basal cell carcinoma and squamous cell carcinoma of the skin. Am
J Epidemiol. 2002 155:614-21.
