Topical MEK inhibition as a new modality for inflammatory skin diseases and cancers
Inflammatory skin conditions affect many people, with a wide range of severities. Common skin disorders such as psoriasis and atopic dermatitis affect close to 20% of the population. Skin lesions associated with bone marrow transplants, and precancerous skin conditions effect less people, but are still detrimental. There are many products on the market available to treat the symptoms of these conditions (such as itchiness or dryness.) The most common treatments involve the use of topical steroids, which reduce the inflammatory response. However, use of steroids comes with steep side effects including skin damage (redness, bruising, and thinning) and can be absorbed and affect internal organs. Because of this, steroids may only be used for a limited time. Other treatments (such as salicylic acid, vitamin D, retinoids, calcineurin inhibitors and antihistimines) are less effective, and all come with side effects ranging from mild discomfort (skin irritation) to more serious conditions (risk of cancer and birth defects.) Inflammatory skin conditions are complex to treat, and current products attempt to alleviate symptoms, but do not always address the underlying cause.
The MEK signaling pathway is abnormally activated in inflammatory skin diseases and cancers, but currently MEK inhibitors have not yet been used to treat non-cancerous conditions. This invention uses a MEK inhibitor to treat a wide range of skin diseases.
Trametinib is an FDA-approved cancer therapeutic approved for use in skin cancers. Because of the detrimental side effects that occur when taken orally and in high doses, it is only approved for malignant cancers. Using an allergen-induced (2, 4-dinitrofluorobenzene or DNFB) dermatitis mouse model, the inventors show that trametinib in a topical form can reduce symptoms of atopic dermatitis.
This invention shows that a topical dose of less than 0.01% of the oral dose used for chemotherapy is effective in reducing skin inflammation in a DNFB-induced atopic dermatitis mouse model, which is a common model for human atopic dermatitis, or eczema.
This reduces a clinically approved cancer treatment to a form that can be safely applied as a home-based therapy.
Other applications include psoriasis (inventors are currently investigating the efficacy of trametinib on a psoriasis mouse model), and other inflammatory skin lesions.
- Trametinib is an FDA-approved drug whose safety and efficacy has already been proven for the treatments of cancer. Repurposing this drug for a topical application, especially at a dose 10,000X less, would pose much lower regulatory hurdles .
- Using a drug that targets a specific pathway in an inflammatory skin condition and can be applied topically is an improvement over some treatments, for example an antihistamine taken orally which effects the entire body’s histamine production.