Antiasthmatic - bimosiamose

Asthma is a major cause of preventable hospitalisations, and its incidence is growing.

Traditionally steroids have been used as a preventative measure, but more recently a range of non-steroidal antiinflammatory drugs, including the leukotriene inhibitors, have been introduced.

Revotar Biopharmaceuticals is investigating bimosiamose, otherwise known as TBC 1269, an alternative type of treatment that prevents leukocytes from migrating into the tissue.1 Cell surfaces are covered with carbohydrate-containing compounds, glycans, which are essential for maintaining cell and body functions, but which can also be involved in disease processes. In chronic inflammatory processes like asthma, an overwhelming stream of inflammatory cells migrates from the bloodstream to the sites of inflammation. This can lead to chronic impairment and tissue injury.

Selectins are proteins that mediate the pathogenic migration of inflammatory cells with glycans and provide a potential drug target. Biosiamose is a glyco-mimetic that inhibits all three selectins that are known to support the inflam-matory process, blocking the inflammation at an early stage. It prevents inflammatory cells from migrating and adhering to the inside lining of the capillaries in injured tissue and has potential as an inhaled therapy for asthma.

A double-blind randomised placebo-controlled crossover Phase II clinical trial was carried out in 12 patients.2 The subjects, who had mild allergic asthma, were given biosiamose (70mg) or placebo by inhalation twice a day for four days. It attenuated the late airways response induced by a standardised allergen challenge test after the last dose, significantly reduced the levels of neutrophils, and increased the numbers of leukocytes in the blood eight hours after the allergen challenge. However, there were no significant differences between the two groups for early airways response.

In another trial, 21 asthmatic subjects were given intravenous treatment with either placebo or 30mg/kg bimosiamose 15 minutes before an allergen challenge.3 It had no effect on early asthmatic response, and a slight effect on late response. Trials continue, with it also being investigated as a potential treatment for psoriasis.