Treatment Reduces COVID-19 Damage in Preclinical Study

May 27, 2021 | 2 min. to read

A novel protein designed by a team of Northwestern Medicine scientists, led by Nephrologist Daniel Batlle, MD, significantly reduced lung damage and resulted in only mild symptoms in mice infected with SARS-CoV-2, while untreated animals in this model all succumbed to the infection. The protein is a variant of angiotensin-converting enzyme-2 (ACE2), the receptor the coronavirus uses to enter and infect human cells.
 
The modified protein intercepts the S spike of the coronavirus and fools it into binding to it, rather than to the real ACE2 receptor, in cell membranes. A prior study was the first proof of concept that a soluble human ACE2 protein is effective in vivo in a preclinical study using an animal model. The soluble ACE2 protein variant developed by Dr. Batlle and colleagues, as part of their longstanding work with ACE2, has been enhanced to have a stronger binding to the virus spike and also to last for days. The study findings should be considered preliminary until it is published in a peer-reviewed journal.
 
“We envision this novel soluble ACE2 protein will attenuate the entry of coronavirus into cells in the body mainly in the respiratory system and, consequently, the serious symptoms seen in severe COVID-19,” says Dr. Batlle, who is also a professor of medicine at Northwestern University Feinberg School of Medicine. “We have converted a lethal disease into a milder lung disease that is fully reversible. The protein could be complimentary to other potential treatments or effective alone.”
 
This new research is an extension of a study previously conducted by Dr. Batlle and his team, titled, A Novel Soluble ACE2 Variant With Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids and published in the Journal of the American Society of Nephrology, which demonstrated the ability of a novel ACE2 protein to neutralize COVID-19 using kidney organoids as a model. The new work, however, uses an improved ACE2 protein bioengineered by Jan Wysocki, MD, PhD, Nephrology and Hypertension, and the team in Dr. Batlle’s lab.
 
This improved ACE2 protein was given to transgenic mice that develop severe COVID-19 manifestations when infected with SARS-CoV-2 and do not survive. Anjana Yeldandi, MD, Pathology, and Ian Gelarden, MD, resident, Pathology, documented a significant improvement in lung histology in animals treated with the new ACE2 protein. “The treated animals had a spectacular response in that all but one survived and recovered,” Dr. Batlle says.
 
Next steps involve the planning of safety studies needed before applying for Investigational New Drug approval for future studies in patients with COVID-19. “The treatment is directed primarily to the lungs but should benefit all the organs of the body that can be affected by COVID-19,” says Dr. Batlle. “To be able to have this treatment available for patients is usually a long process, but we hope that an expedited review by the FDA and appropriate resources will make this possible in the not-too-distant future.”