helping patients with acute lung injury
Acute Lung Injury (ALI) is a rapidly progressing inflammatory disease that leads to the accumulation of fluids in the lung airspace and reduced lung function. ALI and Acute Respiratory Distress Syndrome (ARDS), a more severe form of ALI, affect 200,000 patients every year in the United States, with a mortality rate up to 60%.
The current primary treatment for ARDS is using a mechanical ventilator, but this can further damage the lungs. To date, no pharmacological strategy targeting the inflammatory process has been effective in reducing mortality in ALI/ARDS.
University of Michigan’s Lola Eniola-Adefeso, Ph.D., is developing a novel, particle-based targeted treatment that blocks neutrophils (a type of white blood cell) from migrating into the lungs in response to an infection/injury. Neutrophils are the primary cause of lung inflammation in ALI/ARDS, causing fluid accumulation and lung damage.
The treatment consists of microparticles formed from a biodegradable, biocompatible salicylic acid-based polymer. These microparticles are injected into the bloodstream and interfere with the neutrophils ability to adhere to vessel walls and migrate into the lungs. Secondarily, these microparticles degrade over time, releasing salicylic acid (i.e. aspirin) locally to provided added anti-inflammatory benefit.
“Our preliminary work shows that our proposed approach is promising for limiting disease severity by reducing neutrophil count and inflammation in the lungs while preventing lung bacteria from entering the bloodstream,” says Eniola-Adefeso. “The reduced presence of neutrophils limits the extent of tissue injury, giving the body time to recover.”
Significant Need
Other approaches to the treatment of ALI/ARDS target inflammatory molecules or signals using pharmaceutical agents or antibodies, but most have not been effective. Currently, only mechanical ventilation is available to patients already presenting ALI/ARDS, but mortality is still about 40-60%.
Compelling Science
Microparticles directly interact with neutrophils in the bloodstream, blocking their ability to adhere and migrate into the inflamed tissue, while also releasing salicylic acid locally to reduce inflammation.
Competitive Advantage
The microparticles can be rapidly administered intravenously by a provider upon diagnosis of ALI, and can be easily incorporated into the clinical workflow.
Overall Commercialization
- Intellectual Property – Full utility and PCT patent applications filed. Intellectual property has been licensed to a start-up company.
- Commercialization Strategy – Start-up company formed to develop technology through first-in-human studies, with the ultimate goal of acquisition by a strategic pharmaceutical company.
- Regulatory Pathway – FDA IND for first-in-human study in ARDS patients, followed by a full NDA.
- Product Launch Strategy – Initial indication in ALI/ARDS, with subsequent expansion into other immune-mediated inflammatory conditions.
Milestones
- Conduct in vivo biodistribution and biocompatibility studies of the microparticles in mice
- Determine optimal dosing and administration of the microparticles in a porcine model
- Demonstrate efficacy of the microparticles in a clinically-relevant porcine model of ALI/ARDS
