Bridge Pharma Inc., USA
Keynote: Surgery Curr Res
An AD is not caused by a single gene defect but is a polygenic disorder. Nevertheless, recent AD-drug has very specific mechanisms of action such as for example phosphodiesterase-4 inhibitors and monoclonal antibodies directed against specific cytokines. However, there are different ways to develop drugs than the common mechanistic approach. Thus, more than 40 years ago, the sales of the Generation-1 antihistamine ketotifen (K) suddenly improved when it surprisingly was found that K was effective against AD (and asthma). Unfortunately for the AD-patients, K was the most sedating of all marketed antihistamines and sedation was dose-limiting to 1 mg, bid. We have now found that K has no therapeutic effects in an AD, but K is a severely sedating prodrug to a metabolite, called norketotifen (N), which is potentially both as an anti-inflammatory and an antipruritic drug. N is completely free from sedative effects and is not an immunosuppressive compound. N has been found to be a potent and long-acting ???mast cell stabilizer??? an inhibitor of eosinophil accumulation. N inhibits both histamine-1 and histamine-4 receptors, thereby representing a new type of histamine receptor inhibitor. N potently inhibits both histaminergic and non-histaminergic pruritus. Pharmacokinetically, N is rapidly absorbed in humans after oral administration and has a long plasma half-life allowing once-daily oral dosing. N was found in high concentration in the skin of dogs after oral administration. N is also topically active and rapidly expressed both antipruritic and anti-inflammatory effects after dermal application in a cream to laboratory animals.
Gunnar Aberg obtained his PhD in Pharmacology and his Docent appointment in Applied Pharmacology in Sweden. He was head of Pharmacology at Bofors Nobel- Pharma in Sweden and at Astra-US. He was Director of Pharmacology at Ciba-Geigy, Director and Executive Director of Pharmacology at Squibb and Bristol-Myers Squibb. Gunnar was Vice President and later Executive Vice President of Research at Sepracor until he founded Bridge Pharma, Inc, where he serves as President and CEO. Gunnar is the author of more than 100 scientific publications and the inventor of about 100 US patent and about 400 international patents.