A University of Pittsburgh researcher is developing a novel treatment approach for severe asthma (SA). Through understanding of the role of IFN-g overexpression in airway hyperresponsiveness (AHR) in SA it is possible to develop therapeutic approaches to either regulate IFN-g expression or limit its effects. Development of small molecules or gene therapy to regulate IFN-g expression could substantially improve the lives of patients with SA, reducing complications, hospitalizations and deaths.
Description
The prevalence of asthma is growing globally and results in inflammation and narrowing of the small airways in the lungs causing symptoms including cough, wheezing, chest tightness and shortness of breath. Asthma can be extremely distressing, not only for patients, but their caregivers and families. The majority (>90%) of cases are mild to moderate and can be well managed with medication including low-dose inhaled corticosteroids (CS). However, for a subset of patients (5–10%) classified as having SA, CS therapy alone is ineffective, even in high doses. The economic burden of SA is $28 billion per year in the US alone, and SA impacts the quality of life of millions of people. There is a clinical need to develop novel effective treatments for SA to not only reduce the economic burden associated with increased hospitalization and morbidity but also improve the quality of life of patients with SA and their loved ones.
Applications
- Severe asthma
Advantages
Challenges remain in developing effective treatment to alleviate symptoms in patients with SA. Research has demonstrated that IFN- overexpression in human bronchoalveolar lavage (BAL) cells plays a critical role in SA and contributes to increased AHR and inhibited response to CS treatment. Additional studies also linked the transcription factor IRF5 with SA and may in fact be a predictive biomarker of asthma severity.
The development of small molecules or genetic therapies to target and inhibit IRF5 activity could result in reduced expression of IFN- and improved response to CS therapeutics, allowing for better management of SA in patients.
Invention Readiness
In vivo studies using IRF5-/- mice (i.e., mice deficient in IRF5) in an SA model demonstrated significantly lower levels of IFN- and improvements in AHR compared to wild-type mice. These animals responded well to CS therapy and confirmed that inhibition of IRF5 was a feasible therapeutic approach to treat SA. Additionally, the relationship between the expression of IRF5 and severity in SA models suggests IRF5 could act as a biomarker that enables clinicians to better predict those patients least likely to respond to CS therapy and tailor treatments accordingly. Work is now required to identify and develop therapeutic agents and approaches to selectively inhibit IRF5 activity in patients with SA.
IP Status
https://patents.google.com/patent/US10420792B2
