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Allergen research – present and future

An allergy is a hypersensitivity disorder of the immune system. It is an exaggerated immune reaction to external stimuli such as pollen and is associated with symptoms that range in degree from uncomfortable (hay fever, asthma) to life-threatening (anaphylactic shock). Dr. Thomas Bethke, Medical Director of Nycomed Germany, explains in the following interview how a drug manufacturer approaches the research and development of anti-allergy therapeutics and drugs for the treatment of respiratory disorders.

Dr. Thomas Bethke, Medical Director at Nycomed Germany © Nycomed

Dr. Bethke, Nycomed markets numerous drugs for the treatment of respiratory disorders that are caused by allergies, amongst other things: what is the basis for the idea that leads to the development of such drugs?

Whether an idea relates to completely new therapeutic concepts (so-called leap innovations) or the optimisation of existing treatment methods (so-called step innovations), the development process only starts once demand has been determined. The first and important question that needs to be raised is: is there a therapeutic need or a therapeutic gap that needs to be closed? In other words, are there any patients suffering from allergies, hay fever, asthma or other inflammatory respiratory diseases for whom no effective and safe therapy is available?

Nycomed uses inhalable gluocorticoids for the treatment of asthma. What role do such compounds play?

However much strategic planning you do and however excellent your project management in research and development is, luck always plays a part. Research also means that luck needs to be given a helping hand. Let’s take anti-inflammatory glucocorticoids, which are used for inhalation sprays, as an example. Glucocorticoids, better known as cortisones, are used for the treatment of asthma. It has been shown that some of these glucocorticoids are much better tolerated by patients than other molecules of the same class. With regard to inhalable therapeutics, our scientists are looking for compounds with particular properties that only exert their effect in the respiratory tract. Side effects in the throat (sore throat, fungal infections) are irritating and drug developers will always seek to prevent such things. When a pharmaceutical company has achieved excellent results with a drug used for the treatment of asthma, for example, it goes without saying that this drug will be tested for its efficiency in the treatment of other allergic diseases, e.g. allergic rhinitis (hay fever) affecting the nose.

Where in the organism do these molecules exert their effect and what kind of effect do they have?

Inhalable glucocorticoids have a strong anti-inflammatory effect. This effect is achieved through the inhibition of a large number of genes coding for pro-inflammatory proteins and through the activation of a slightly smaller number of genes coding for anti-inflammatory proteins. In addition to the inhibition or activation of genes, glucocorticoid receptor molecules in the cells, which work according to the key-lock principle, are also able to delay the progression of inflammatory processes. Inhalable glucocorticoids reduce the flow of liquid mucus through the nose, as well as reducing itching, sneezing, and swelling of the nasal mucosa. The allergic reaction becomes weaker and the patient can breathe more easily.

Inhalable, anti-inflammatory glucocorticoids are used for the treatment of asthma. © Nycomed

Can you tell me more about the role of galenic formulation in the development of anti-allergy drugs?

Galenic formulation plays a key role in the drug development process. The development of a medicine that can be applied safely and gently (spray or droplets) plays an important role in the willingness and ability of a patient to take a certain drug – something that is referred to as patient compliance. Depending on the target site, in this case the nose, in vitro and in vivo tests are carried out to find out the instruments and liquids that are best tolerated by the nasal mucosa and ensure that as much of the active agent as possible reaches the nasal mucosa.

What does the further development of drug formulation depend on?

Researchers are of course always interested in improving their drugs, i.e. making them more effective, safer and more tolerable. In addition, researchers are always seeking to make use of rapid technological process. A new drug may just have been launched on the market, but it can be safely assumed that it is already undergoing optimisation, e.g. alteration of dose strength, other formulation (e.g., in combination with other solvents), a new application device or use in a completely different field of indication. As is the case with glucocorticoids, drug developers always have other potential fields of indication in mind. Therefore, the answer to your question relates to other potential indications that a new drug can be used for. For example, can allergic skin alterations or chronic inflammatory bowel diseases be treated with this new substance? There are many common inflammatory respiratory diseases besides asthma, including chronic obstructive pulmonary disease (COPD). With asthma research as a starting point, pharmaceutical researchers have spent several decades on the search for new anti-inflammatory substances. The concept of phosphodiesterase (PDE)-4 inhibition was worked on at the Nycomed laboratories in Konstanz and, as a result, Nycomed has received marketing authorisation for a PDE-4 inhibitor.

Are you focusing on the development of additional drugs for the treatment of respiratory diseases that are the result of allergies?

Without ongoing drug research, the history of medicine would be rather a short story, I think. As you know, we are barely able to treat the symptoms of the majority of diseases, let alone the cause of disease. This is also true for allergies and inflammatory respiratory diseases. I believe that in future promising therapeutic approaches will be developed for the treatment of diseases such as allergy-related asthma that are known to be related to genetic factors given that it is known that the likelihood of developing allergies is something that is inherited.

Further information:

Jürgen Schneider
Director Communications Germany
Tel.: +49-(0)7531/84-3021
Fax: +49-(0)7531/84-93021

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/allergen-research-present-and-future