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Chronic obstructive pulmonary diseases curable in the future?
Chronic obstructive pulmonary disease (COPD; also known as smoker's cough) has so far been considered incurable. However, scientists have now identified two new drug candidates that could represent a breakthrough in the treatment of COPD. The active substances prevent the inflammatory processes in the lungs and thus prevent the disease from progressing.
The previously incurable disease COPD is one of the most common causes of death worldwide and is mostly caused by smoking, the researchers explain in a communication from the Ruhr University Bochum (RUB) on the current study results. The two anti-inflammatory substances identified had proven to be effective approaches against chronic obstructive pulmonary disease in the preclinical studies. The study results were published in the journal "Journal of Allergy and Clinical Immunology".
More than 10 percent of the world's population suffer from COPD
COPD is characterized by chronic inflammation of the airways. Over time, this leads to irreversible damage to the lung tissue and lung function is increasingly impaired. "According to expert estimates, 11.7 percent of the world's population currently suffer from chronic obstructive pulmonary disease," said the RUB. The disease usually develops from chronic bronchitis and is mainly caused by tobacco smoking. Therapies available today can relieve symptoms and slow the progression of COPD, but they cannot stop it.
Inflammatory processes crucial for the course of the disease
“Apart from a preparation that can be used for very severe COPD in a certain group of patients, there are currently no other causal therapies that are not based on steroids and are aimed at combating the inflammation, which is central to the progression of the disease "; the scientists report. The inflammatory processes are regulated by special enzymes, so-called protein kinases. These “are indirectly overactivated by smoking, by COPD-characteristic inflammatory substances and by respiratory infections,” the RUB said. As a result, the body produces even more inflammatory substances, which makes a decisive contribution to the progression of the lung disease.
Available active substances have so far been unsuitable
Available anti-inflammatory agents such as inhaled corticosteroids, according to the RUB, help with other chronic inflammatory lung diseases and can prevent the symptoms from worsening acutely. However, therapy with them is currently only recommended in combination with bronchodilators and for patients in whom the symptoms often worsen.
Looking for new active ingredients
The research team led by private lecturer Dr. Jürgen Knobloch from the pneumological clinic at the Bergmannsheil University Medical Center in Bochum, Prof. Dr. Andrea Koch from the University Clinic of the Ludwig Maximilian University in Munich and Prof. Erich Stoelbe from the Lung Clinic in Cologne-Merheim have now looked for new anti-inflammatory agents for the treatment of COPD together with scientists from RespiVert, a subsidiary of Janssen Biotech.
What are narrow spectrum kinase inhibitors?
Here the scientists saw a promising approach in the so-called “narrow spectrum kinase inhibitors” (NSKI for short). These inhibit the protein kinases. Two special NSKIs - called RV1088 and RV568 - were identified by RespiVert and made available for the investigations. The scientists tested the NSKI on cell cultures and compared their effectiveness with a conventional corticosteroid and various single protein kinase inhibitors, which are also considered as drug candidates, reports the RUB.
Convincing effect of the new NSKI
In the trials, the two NSKIs proved to be more effective in inhibiting the production of inflammatory substances compared to the comparison substances. "Our study shows that NSKIs are promising candidates for developing urgently needed anti-inflammatory therapies for COPD," emphasizes Dr. Knobloch. The first successes had previously been achieved in preclinical models with the single protein kinase inhibitors, but it had already been indicated that “the effect would not be sufficient in clinical use.” With such a specific inhibition, other protein kinases would simply regulate inflammation take over.
Breakthrough in COPD treatment
The scientists therefore looked for active substances that covered a broader spectrum of protein kinases. They tested drug candidates "that target not only one protein kinase or a family of protein kinases, but a specific spectrum of several protein kinase families," explains the RUB. The active ingredients were then tested on cultured primary smooth airway muscle cells from COPD patients. The results make the researchers optimistic. "The new potential drugs could be a breakthrough in the treatment of COPD," the study authors concluded. (fp)