The Problem
Asthma Today
Asthma is one of the most common respiratory diseases in world affecting 10% of the world’s population, 20 million people in the US alone including 400,000 deaths. Asthma is on the rise, increasing by 19% in the US since 2001! Most people someone with asthma but what might not be apparent is that can be very severe for a subset of patients of asthma. These patients experience wheezing, cough and shortness of breath every day seriously affects their ability to work, or go to school. Asthma attacks, where these symptoms become so severe that additional medical care is needed like a hospitalization or an emergency department visit, create a huge burden for our patients with severe asthma and a cost of close to $82 billion in health care expenditures and lost productivity. Despite our advances in understanding of the immunology of asthma with improved medications and now biologics that target specific inflammatory pathways, we have not come close to eliminating asthma attacks
Despite care and management, the asthma attack persists.
Patients With Asthma Know The Impact On Daily Life Or When Symptoms Flare Up.
Asthma is the most common inflammatory lung disease both children and adults worldwide. Health care burden is significant due to severe symptoms of wheezing, cough and shortness of breath due to airway inflammation and bronchoconstriction leading to urgent care and emergency department visits as well as hospitalization. The financial burden is enormous, amounting to $80 billion in expenditures yearly when direct health care costs and lost productivity due to time away from work or school are considered. In addition, many patients report lifestyle limitations, such as participation in exercise and other physical activities, owning a pet or even taking a holiday.
Asthma is complex with causes varying from person to person.
Triggered by infection, environmental allergens or other stimuli, asthma remains poorly understood and difficult to manage due to the heterogeneity of the disease. In addition, several different types of asthma have been described. These include: allergic, eosinophilic, aspirin exacerbated asthma (all type 2 asthma), non-allergic, obesity related, infection and environmental exposure induced asthma.
Current treatments rely on steroids and carry a host of side effects
Steroids have limited efficacy. While asthma treatments have been largely unchanged for the last 50 years, it is an unfortunate reality that asthma remains uncontrolled in more than half the patients receiving standard asthma medication. The rise in asthma prevalence together with the need for better control of exacerbations and the desire to reduce long-term side effects of commonly used asthma drugs have elevated the need for new classes of asthma drugs. Such drugs and treatments for asthma to address untreated populations would have immediate nation-wide and world-wide impact.
Current asthma therapies cause a host of side effects. There are concerns surrounding the side effects from long-term use of the most frequently prescribed FDA-approved asthma therapies. These treatments include: corticosteroids (inflammation reduction) which can cause hoarseness, weight gain, osteoporosis and cataracts. Oral corticosrteroid used to treat asthma attacks, while effective are particulary concerning: even a single course can increase the risk of developing sepsis; Other treatments include short-acting β2-agonists (fast response bronchodilator) and long-acting β2-agonists (a long-acting bronchodilator ) can cause rapid heart rate, tremulousness and electrolyte abnormalities. Anticholinergics (bronchodilator) can cause dry mouth and increase the risk of glaucoma and anti-leukotrienes (supplemental anti-inflammatory) have been given a black box warning for causing suicidal ideations. .
A treatment derived from an endogenous protein
Surfactant Protein A (SP-A) is a very well-known innate immune modulator that is produced and secreted by several different types of cells in the lung. SP-A is the major protein component of the pulmonary surfactant lining fluid in the airways and as such serves as one of the first lines of defense against inhaled insults throughout the upper and lower airway. In the lung, SP-A functions in pathogen clearance and in mediating inflammatory processes. The mature SP-A protein is a very large hetero-oligomeric product that resembles a bouquet of flowers. Due to this large size, mature SP-A cannot be given in an inhaler device. Thus, small peptidomimetics derived from active regions of the endogenous SP-A lung protein offer a unique and novel approach to the treatment of asthma. By harnessing and optimizing the natural activity of this lung protein, we will be able to deliver SP-A-derived peptidomimetics to regulate key innate immune functions in the lung and drive protection against asthma exacerbation.
SP-A derived small peptide therapeutic
For the lungs, surfactant protein-A (SP-A) is the first line of defense when encountering viral, allergen, or environmental irritants.
We have identified a 10-20 amino acid sequence that can recapitulate the activity of full-length SP-A in reducing inflammation in particular types (phenotypes) of asthma.
Our therapeutic strategy involves identifying and enhancing the natural activity of SP-A and optimizing formulations into a deliverable format with increased stability and efficacy for treating asthma.