Chitinase: new drug target in asthma?
response suffered by those with asthma has been shown to induce a
specific enzyme which if neutralised, could eliminate the
inflammation and hyperresposiveness of the airway, giving hope to
asthma sufferers, writes Wai Lang Chu.
The discovery of this enzyme, acidic mammalian chitinase (AMCase), could result in the development of a drug that focuses on the underlying pathogenesis of the disorder.
In addition, the pathway known as T helper-2 (Th2) - specific, interleukin - 13 (IL-13) - mediated pathway, is central to many allergic responses of the respiratory system such as ulcerative colitis. An excess of IL-13 is thought to be a trigger for asthma attacks in patients with the disease.
Jack Elias, professor of medicine at Yale University and one of the authors of the study, told DrugResearcher.com that "only time will tell but as a drug target and treatment it does point in that direction. The additional studies we have carried out on animal models and human tissues show decreased levels of chitinase."
Interestingly, humans have chitinase genes, but these have been considered an evolutionary throwback. The enzymes are common in simple organisms, such as worms and flies, where they are thought to serve in the defense against parasites. One asthma theory suggests that the disease is caused by the body responding to a parasitic threat that is not in fact there.
"The TH2 pathway is common in many respiratory allergies so this discovery has the potential to help all disorders mediated by this pathway," added Elias.
"We are currently in development with a biotechnology firm to develop human antibodies that halt the immune response that is involved with respiratory disorders."
With the worldwide prevalence of asthma now reaching epidemic proportions afflicting over 50 million individuals globally and continuing to escalate at an alarming rate, there is a need to develop new therapeutics for asthma, particularly those to control the underlying and untreatable inflammatory and destructive processes that cause its progression.
In addition, asthma is a major cost to healthcare systems comprising over 1 per cent of the total healthcare bill in the USA - the highest for any single disease.
Currently the anti-asthmatic market is well served by existing therapies, such as the beta-agonists and corticosteroids which can treat 95 per cent of asthma patients. While existing drugs, especially inhaled corticosteroids and combination inhalers, are effective, the side effects which include cataracts, loss of bone mineral (osteoporosis), muscle weakness, decreased resistance to infection, high blood pressure and thinning of the skin are a drawback which some drug companies are keen to improve upon.
More seriously, inhaled corticosteroids can affect children's growth, a worrying fact considering asthma's alarming rise in adolescents. Consequently, any new drug therapy wanting to attain commercial success needs to offer significant advantages over currently marketed therapies.
The primary longer term goals are to develop orally active agents with acceptable side effect profiles and also preventative therapeutics. The inhaled beta agonists for airway obstruction only tackle the symptoms of the disease.
One other class of drugs that is showing promise are the leukotriene antagonists. First launched in the 1990s, they were the first new group of asthma drugs to be introduced for over 20 years, but while useful additions to the armamentarium cannot offer the potency of corticosteroids.
