Novel drug for asthma identified

A new study, titled "Transgelin-2 as a therapeutic target for asthmatic pulmonary resistance" and published in the journal Science Translational Medicine on 7 Feb 2018, demonstrates that a drug called TSG12 could have therapeutic effects against respiratory disorders like asthma.

This work is a collaboration of Shanghai University of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine, Changzhou University in China, Georgia Regents University, and Rutgers New Jersey Medical School in the USA.

Asthma is a chronic inflammatory disease of the lungs' airways. The disease attacks people of all ages and often manifests as wheezing, coughing, chest tightness, and shortness of breath. Many factors can set off an asthma attack, such as exposure to irritants in the air (dust mites, pollen, mold, and pet dander) as well as being in extreme weather conditions. Some diseases can also trigger asthma. Further, genetic ancestry matters in asthma susceptibility.

Disease severity of asthma varies from one person to another. For people suffering from severe asthma, currently used treatments have limited efficacy or exhibit serious side effects. Thus, there is a dire need for safer and more effective anti-asthma drugs.

Dr. Luis Ulloa, associate professor of Rutgers New Jersey Medical School, who is one of the senior authors of the new study, has been studying the pathogenesis of infectious and inflammatory disorders for years. One aim of his research is to use research findings to develop novel treatments for these diseases.

Previous studies have shown that inhibiting a protein called metallothionein-2 (MT-2) in lung tissues results in the elevated pulmonary resistance. Dr. Ulloa's team found that MT-2 is effective in relaxing airway smooth muscle cells (ASMCs), reducing pulmonary resistance, and opening the airways.

MT-2 is one of the isoforms of the protein metallothionein (MT). MTs have a high content of cysteine residues and are low in molecular weight. These proteins bind various heavy metals and are transcriptionally regulated by both heavy metals and glucocorticoids. They act to control heavy metal concentration and oxidative stress.

The researchers observed that asthmatic lung tissue exhibited lower MT-2. Mice lacking MT-2 were much more likely to develop asthma, whereas an MT-2-agonist known as TSG12 effectively improved symptoms of asthmatic mice. Further, the research also provided insights into the mechanism of the action of TSG12.

These data demonstrate the potential of TSG12 as a treatment for asthma. The advantages of TSG12 over currently used treatments include high efficacy and non-toxicity. Although it is too early to use TSG12 in the clinic, the study provides a novel therapeutic strategy for this major health concern.

Asthma is associated with a significant economic burden. There is a sharp increase in the global prevalence, morbidity, and mortality of asthma. Currently, about 300 million people are suffering from asthma. The majority of asthma-related severe disability and deaths occur in low and lower-middle income countries. This is, in part, due to limited access to care and essential medications.
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