Asthma


Asthma is a chronic (long-term) lung disease that inflames and narrows the airways. It affects the sensitivity of the nerve endings in the airways so they become easily irritated. In an attack, the lining of the passages swell, causing the airways to narrow and reducing the flow of air in and out of the lungs. For patients, this translates into recurring periods of wheezing (a whistling sound when you breathe), chest tightness, shortness of breath, and coughing. Asthma affects people of all ages, but it most often starts during childhood.

In Western Europe, asthma has doubled in ten years, according to the UCB Institute of Allergy in Belgium. In addition to causing suffering, the human and economic burden associated with this condition is severe. For example, worldwide, the economic costs associated with asthma are estimated to exceed those of TB and HIV/AIDS combined (1).

Asthma cannot be cured, but can be controlled by avoiding substances and agents triggering asthma symptoms and through the use of existing treatments. However, those treatments are far from ideal, and their side effects are widely documented. Additionally, a fraction of asthma patients (“refractory patients”) respond poorly to glucocorticoids treatment, or require such high doses that side effects become a major concern. Therefore, new, steroid-sparing options for the treatment of asthma are necessary.

Although asthma does not kill on the scale of chronic obstructive pulmonary diseases (COPD), failure to use appropriate drugs or comply with treatment, coupled with an under-recognition of the severity of the problem, can lead to unnecessary deaths, most of which occur outside hospital.

The greatest challenges in the treatment of asthma include finding drugs with novel modes of action for preventing disease progression and for treating refractory patients. It is expected that 10 to 15 new drug products will be launched for asthma / COPD by 2020. However, it is already known that products currently undergoing clinical development are minimally different from current therapies. Consequently, the important medical need of many asthma patients, including refractory patients, will likely remain unmet. This is the reason why the new molecules investigated in the context of Primomed are of special interest.

The Primomed approach


In the context of asthma, Primomed will evaluate two molecules with different and novel modes of action, which could achieve disease modifying potential in asthma and provide a solution for refractory patients.

One of those molecules is a locally-acting ROCK inhibitor.

ROCK belongs to a superfamily of proteins known as protein kinases, which play a fundamental role in many cellular processes. Interestingly, ROCK plays a role in inflammatory and autoimmune reactions, but also in smooth muscle contraction. Concretely, this means that a single compound reducing the activity of ROCK (a ROCK inhibitor) could simultaneously have anti-inflammatory and bronchodilatory effects. Additionally, the biological processes involving ROCK differ from those that are affected by corticosteroid drugs. ROCK inhibitors could therefore provide novel treatment options for refractory patients.

The potential of ROCK for the treatment of asthma is well described (2). However, it has so far only been explored to a limited extent. The reason for this is that ROCK inhibitors cause a rapid and strong decrease in blood pressure once they get into the blood circulation. Even when a ROCK inhibitor is delivered directly to the lungs (e.g. with an aerosol), the amount of compound that leaves the lung and enters the blood circulation could still cause ROCK-associated side effects.

The selected ROCK inhibitor is a locally-acting compound. This means that it has strong activity against ROCK, but was designed so that it is very rapidly degraded once it enters the blood circulation. This innovative approach could avoid the side effects commonly associated with ROCK inhibitors and yield a new drug for the treatment of asthma, with a unique mode of action.

The results obtained within Primomed will be used in progressing this ROCK inhibitor towards clinical trials, so that patients can actually benefit from this novel therapeutic approach.

References


  1. http://www.who.int/mediacentre/factsheets/fs307/en/
  2. Schaafsma, D. et al. Am J Physiol Lung Cell Mol Physiol. 2008 Jul;295(1):L214-9