Periodic Reporting for period 1 - MUC2GO (Novel treatments for the mucus accumulation at chronic lung diseases)
Période du rapport: 2023-03-01 au 2024-08-31
Many of the respiratory diseases include mucus overproduction and stagnation. This include COPD, acute and chronic bronchitis, cystic fibrosis, about half of the ones with asthma. COPD has now become the third reason for death where both vascular-heart diseases and cancer are making fast improvements, whereas there has not been the same development for COPD. A major reason for this is the limitations in understanding the lung mucus system in health and disease.
We have made progress in this and shown that the normal lungs do not have as misunderstood a mucus coating and is instead cleaned by mucus bundles from the submucosal glands that sweep the surface and transport the debris and bacteria to the larynx and by this keep the lungs essentially free from bacteria and dust. When the lungs are exposed to virus, more bacteria or inhaled particles, the lung respond by increased number of mucus producing cells that form an attached stratified mucus layer. This layer is similar to the protective mucus layer discovered by us in the large intestine. This mucus layer will trap bacteria that will remain in the lungs due to the mucus attachment, something that cause inflammation and destruction of the lung, typical for many lung diseases.
Our basic research efforts have been focused on understanding the molecular details of the mucus layer at disease, to such a level that novel drugs can be developed to detach the disease mucus layer allowing an efficient cleaning of mucus and bacteria from the lungs. The main goal is to develop several generations of novel efficient mucolytic drugs for the common lung diseases.
We have made progress in this and shown that the normal lungs do not have as misunderstood a mucus coating and is instead cleaned by mucus bundles from the submucosal glands that sweep the surface and transport the debris and bacteria to the larynx and by this keep the lungs essentially free from bacteria and dust. When the lungs are exposed to virus, more bacteria or inhaled particles, the lung respond by increased number of mucus producing cells that form an attached stratified mucus layer. This layer is similar to the protective mucus layer discovered by us in the large intestine. This mucus layer will trap bacteria that will remain in the lungs due to the mucus attachment, something that cause inflammation and destruction of the lung, typical for many lung diseases.
Our basic research efforts have been focused on understanding the molecular details of the mucus layer at disease, to such a level that novel drugs can be developed to detach the disease mucus layer allowing an efficient cleaning of mucus and bacteria from the lungs. The main goal is to develop several generations of novel efficient mucolytic drugs for the common lung diseases.
The research has been focused on structural work on the main components in mucus and to understand how these form long polymers and interact to form a stratified mucus layer. There has been progress, although these molecules are enormous and difficult work with. We have learned that calcium ions are very important for the molecules structure and interaction stability.
The main focus has been to analyze the effect of one potential drug on animal models in mice with stagnated and attached mucus. This has been performed in several steps by instillation, inhalation, and nasal instillation studies followed by analysis of mucus obstruction and removal.
The main focus has been to analyze the effect of one potential drug on animal models in mice with stagnated and attached mucus. This has been performed in several steps by instillation, inhalation, and nasal instillation studies followed by analysis of mucus obstruction and removal.
A first drug, GlaPep8, has been developed and evaluated in its efficiency in clearing mucus accumulated in the mice with induced mucus accumulation. The compound is patented in US and Europe. A new company, MucoLife AB, has been formed to develop this drug into first modern mucolytic drug in humans. The drug is very effective and much better than any alternatives or competitors. MucoLife AB is now working on attracting investors in EU or US for in-house development into at least phase 2 studies in humans or out-licensing to a major pharmaceutical company.
A second drug based on interfering and disrupting specific interactions between mucins and related molecules within mucus is explored. The screening and evaluation is based on specific knowledge of the structure of these molecules. A number of candidates have been identified and work is now on-going to validate efficiency.
We expect to have a portfolio of novel compounds designed to dissolve and detach attached mucus as lung diseases as COPD, cystic fibrosis, acute and chronic bronchitis and asthma.
A second drug based on interfering and disrupting specific interactions between mucins and related molecules within mucus is explored. The screening and evaluation is based on specific knowledge of the structure of these molecules. A number of candidates have been identified and work is now on-going to validate efficiency.
We expect to have a portfolio of novel compounds designed to dissolve and detach attached mucus as lung diseases as COPD, cystic fibrosis, acute and chronic bronchitis and asthma.