Biotechnology

The future of asthma treatment: is a cure possible?

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For some 300 million people worldwide, popping their inhaler — a medical device that delivers medication into the lungs to open constricted airways — before inhaling medication into their mouth, is a typical response to wheezing, which is exacerbated by an asthma attack.

While inhalers offer momentary relief, however, there is no cure. But some recent research shows therapeutic promise. As we observe World Asthma Day on May 2nd, let’s take a look at the latest advances in asthma treatment.

Often triggered by factors such as allergies, sinus infections, pollen, and extreme weather conditions, it manifests itself through symptoms such as shortness of breath, chest tightness, and persistent coughing.

And although current asthma treatments such as inhaled corticosteroids and allergy shots, as well as the new US Food and Drug Administration (FDA)-approved Airsupra inhaled aerosol provide quick relief from these symptoms, Cliff Han, a former biologist and founder of the allergy lollipop who US-based manufacturing company AllerPops, believes the microbiota may be the key to a cure.

Lungs and the microbiome

“The microbiota associated with humans is increasingly being recognized as an important part of our health,” said Han. Observing the gut microbiome, people have proposed a gut-brain axis and a lung axis, he added. “Recently, researchers have shown that deep inside the lungs are not sterile and have identified a distinct microbial composition associated with asthma.”

A Study conducted by AllerPops explores possible microbiota-related causes and treatments for allergic rhinitis – inflammation of the nose caused by an allergen. It was found that common allergies can occur when there is a deficiency of oral probiotics. Simply put, restoring gut health is essential for managing allergic asthma.

The results showed that the lack of beneficial bacteria such as Streptococcus and Veilonella in the oral and nasal cavities causes allergies.

“Our study of the oral microbiota in relation to allergic rhinitis suggests a close interaction between several bacteria and our immune system. Those beneficial bacteria tend to calm our immune system so they can live peacefully with us. That interaction also reduces inflammation against allergens,” says Han, who has developed a prebiotic lollipop, which is an ingredient supplement that not only relieves allergy symptoms but also helps control asthma in nearly 80% of cases.

Additionally, the research led to the Negative Trigger Theory (TNT), which postulates that oral probiotics are negative triggers that cause the host and microbiota to reconcile with one another. Therefore, modulating the microbiota with the immune system can treat, and more than that, cure allergies as well as autoimmune disorders, according to the study.

Han said: “Managing the microbiota will have great potential to improve our health and, in many cases, cure our chronic afflictions. The key is to identify which microbiota to target and how to manage it more efficiently and sustainably.”

Another recently Study led by researchers at the University of British Columbia in Canada validated Han’s research on the relationship between lung and gut microbiota. Since most of the research has focused on the relationship between gut bacteria and viruses and the immune system, this study has also looked at how fungi and archaea can influence inflammation in the lungs, illustrating how different microbial compositions are related to asthma.

Despite containing less than one percent of the gut microbiome, mold has the potential to impact microbial ecology, according to the study. Although the mechanism has not been confirmed, fungal dysbiosis – an imbalance in the composition of fungi – in the gut microbiota of infants has been linked to asthma symptoms.

Han revealed that the microbiota associated with humans is increasingly being recognized as an important part of our health.

Lifestyle change and asthma prevention

As the saying goes “prevention is better than cure”, the risk of developing asthma can be reduced by enjoying a good night’s sleep, according to a study conducted by Shandong University in China. The study revealed that a healthy sleep pattern, along with a low genetic risk, can prevent about a fifth of total asthma cases. After mapping the genetic makeup of all participants and monitoring their sleep schedule and the occurrence of insomnia and night snoring, the risk of asthma was significantly reduced. For those with healthy sleep patterns and a low genetic risk, the chance of developing asthma fell by 44%, for those with medium risk, the chance decreased by 41%, while for those with a high genetic risk, it was still trimmed by 37%.

While lifestyle changes can be beneficial with managing risk, environmental factors also play an important role. And to speed up the research, a study by the Karolinska Institutet in Sweden drew attention to the importance of clean air and lung capacity. “Fortunately, we have seen decreases in air pollutants and improvements in air quality in Stockholm over the last 20 years,” said Erik Melen, one of the study’s authors, pediatrician and professor in the Department of Research and Clinical Education. at the Karolinska Institute.

A 20% reduction in the risk of impaired lung function was observed in children in Stockholm, as a result of breathing clean air.

Melen said: “This is very important because the lung function that children and adolescents develop as they grow older continues into adulthood,” adding that, “If you have reduced lung function as an adult, you are at greater risk of developing chronic lung disease, diseases like COPD (chronic obstructive pulmonary disease), cardiovascular disease and premature death. So by improving air quality, we reduce the chances of children developing chronic diseases later in life.”

This could indicate a lower risk of asthma, although more research needs to be done. From the results of subsequent studies, emission control measures can be taken into account for urban planning policies to support the health of urban communities in particular.

Meanwhile, precision medicine is being heralded as a new approach to asthma treatment, let alone to treat a different disease. Digital asthma biomarkers such as eNose can assess asthma control – the degree to which symptoms of the disease are reduced by therapy – to tailor asthma treatment. A study proved that the eNose analysis is accurate, with the ability to discriminate between people diagnosed with this disease and those who do not have asthma, making it a non-invasive tool for detecting asthma.

Another important biomarker is eosinophils. Eosinophils are white blood cells (WBC) that indicate an allergic reaction when their levels are high in the blood. A high blood eosinophil count of more than 300 cells/μL can evaluate the efficacy of drugs such as mepolizumab and omalizumab to treat asthma. These biomarkers can predict asthma treatment success and in turn, drive treatment choices for patients.

Inhaler-free era for asthma treatment?

Another growing study in asthma therapy research is being conducted by US-based Arrowhead Pharmaceuticals. In April 2023, the company announced interim results for its ongoing phase 1/2 clinical study of the investigative RNA interference (RNAi) ARO-RAGE, to reduce receptor production for advanced glycation end products (RAGE) for the treatment of asthma.

“Reducing RAGE protein expression in lung epithelial cells to levels demonstrated by ARO-RAGE to date in this study has the potential to treat patients with asthma and other inflammatory lung diseases in completely new ways. RAGE represents a promising target for intervention because its activation has been implicated as a proximal regulator of the inflammatory cascade in the asthmatic airway, and thus silencing RAGE can produce potent anti-inflammatory effects,” said Matthias Salathe, professor, Pulmonary, Critical Care and Sleep Medicine , and vice chancellor for Research at the University of Kansas Medical Center.

The trial showed positive results showing an average maximum reduction of soluble RAGE of 90% at a dose of 92 mg, and for doses of 10 to 44 mg, the response ranged from 31% to 59%.

In addition, other more permanent asthma treatments, especially for those who do not respond well to steroids, focus on pericytes movement. Pericytes, a type of stem cell found in the lining of blood vessels, tend to travel to the walls of the airways during an inflammatory reaction. These pericytes develop into cells, thickening the walls of the airways and making them less flexible. Because pericyte movement is controlled by the CXCL12 protein, researchers at Aston University in England, have tested the molecule LIT-927, which targets protein expression.

In a successful trial performed on rats, symptoms completely disappeared after two weeks when treated with LIT-927, and a marked difference in airway size was observed, with rats given LIT-927 developing thinner airway walls, when compared with those given LIT-927. not treated with the drug candidate.

While this has the potential to be a long-term solution for asthma, more research is needed before the efficacy of the treatment is measured in humans.

Although many still rely on corticosteroids – which can have adverse effects after long-term use in some people – with more research targeting the various endotypes of asthma, we may be close to recovery. And with developments related to the causative factors, preventive measures can also be the answer.

New technologies related to asthma treatment:

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