Psoriasis is a skin condition that involves a serious impairment of the skin barrier accompanied by over stimulation of the immune system.
The National Institutes of Health estimates that 7 million in the U.S. are afflicted by psoriasis. Approximately 1 to 2% of people in the USA,
5.5 million have plaque psoriasis, the most common form. Psoriasis can also be associated with psoriatic arthritis, which leads to pain and swelling
in the joints. Plaque psoriasis involves red skin covered with silvery scales. Plaque psoriasis affects both children and adults with a first peak
in individuals aged 16 to 22 years and a second peak in individuals aged 57 to 60 years. The cause of psoriasis is unknown but plaque psoriasis is
the result of excessive epidermal cell proliferation and defective epidermal differentiation that results in a compromised skin barrier. The
defective skin barrier likely contributes to increased environmental exposure that results in altered regulation of the immune system.
The current market for treatment of psoriasis is above $3 billion dollars (Melnikova, Nature Reviews, Drug Discovery, 8, 767-768, 2009). Topical
treatments ($850 million market) include steroids, vitamin D analogs, retinoids, tars, phototherapy, and (in Europe) monomethyfumarate. Biologics
($2.5 billion market) include alefacept, efalizumab, adalimuab, entanercept, and infliximab. While biologics have shown strong benefit in psoriasis, significant safety concerns involving serious opportunistic infections that result from immune
suppression have been reported. For example, Raptiva has been removed from the market due to safety concerns and Enbrel has received the FDA "black box" warning
about serious infections including tuberculosis. The safety concerns for biologics are such that their use should be limited to severe cases of psoriasis where
the benefits justify the risk. This points out the need for better agents for mild to moderate plaque psoriasis where the safety risks do not warrant the use of biologics.
NPI research has identified a niacin receptor in skin involved in epidermal differentiation/skin barrier formation and modulation of immune function. This is of great
interest in light of the recent discovery that monomethylfumarate (MMF, Fumaderm), an effective psoriasis drug widely used in Europe, binds the niacin receptor
(Tang et al., Biochemical and Biophysical Research Communications, 375, 562-565, 2008). Indeed, the authors of the study concluded that niacin should be effective
for treatment of psoriasis. It is important to note that although MMF is an effective psoriasis drug that it has poor tolerability, causing the skin flushing that limits
the tolerability of niacin, which is likely due to the same mechanism as niacin. The known mechanisms of Nia-114 combined with the lack of skin flushing offers the likely
and exciting possibility of a safe and well tolerated treatment for plaque psoriasis.
