Neurologists are researching whether a novel immunomodulatory treatment, OP-101, can dampen lung and brain injury in hospitalized COVID-19 patients through a clinical trial at The University of Texas Health Science Center at Houston (UTHealth).
UTHealth is one of several sites throughout the country for the Phase II trial, called PRANA. Houston site patients will be recruited from Memorial Hermann Southwest Hospital and Memorial Hermann Memorial City Medical Center.
OP-101 is an investigational compound developed by Ashvattha Therapeutics to selectively attack the proinflammatory macrophages and microglia, which are the immune cells responsible for hyperinflammation, lung injury, and multi-organ failure caused by infections.
“We see this type of hyperinflammation in a number of neurological disorders, including Parkinson’s and Alzheimer’s disease,” said Aaron Gusdon, MD, an assistant professor in the Vivian L. Smith Department of Neurosurgery at McGovern Medical School at UTHealth and principal investigator of the Houston site of the study. “Now we’re seeing the same activation of the innate immune system in COVID-19 patients that drives production of proinflammatory cytokines, which can contribute to patients becoming rapidly critically ill. OP-101 has shown to robustly suppress hyperinflammation in a number of different disorders, so we’re investigating if this targeted approach can help patients with severe cases of COVID-19 as well.”
Unlike single agent approaches, like antibodies, that address only one pathway, the treatment is intended to seek out and selectively shut down cells that are proinflammatory and restore the macrophages to a normal state.
“The hope is that since it only targets the activated component of the innate immune system, it will have fewer side effects and less risk of a concurrent infection compared with some steroids and antibodies that broadly suppresses the whole immune system,” said Gusdon, a neurologist with UTHealth Neurosciences.
“In COVID-19 patients, we know the lungs and sometimes the brain become severely inflamed,” said Louise McCullough, MD, PhD, professor and Roy M. And Phyllis Gough Huffington Distinguished Chair in the Department of Neurology at McGovern Medical School and co-investigator of the OP-101 Houston site. “We’re seeing that trend play out in the long-hauler patients, as the inflammation can lead to long-term symptoms like confusion, fatigue, and depression. We’re interested to see if selectively targeting the activated cells in the lungs, blood, and brain, can help dampen the cytokine storm and possibly prevent the consequences of lung and brain injury for these patients down the road.” McCullough is also the co-director of UTHealth Neurosciences and chief of the Neurology Service at Memorial Hermann-Texas Medical Center.
McCullough is treating patients with neurological long-hauler symptoms at the UT Physicians Post-COVID-19 clinic, which is part of the UTHealth COVID-19 Center of Excellence and was the first post-coronavirus clinic in Houston.
At the Houston sites, seven patients have been enrolled so far, and researchers are seeking two to four more. The national study will enroll approximately 24 patients.
“We’re proud to offer some of the most innovative care not only to patients in the Texas Medical Center, but in surrounding sites as well,” McCullough said.
Patients will be randomized to one infusion of OP-101 or placebo, in addition to standard-of-care therapy. Researchers will evaluate whether the treatment reduced inflammation, improved fever and oxygenation, and reduced the number of days without a ventilator, or time in the intensive care unit.
This research builds on a strong foundation of COVID-19 neurological research that McCullough and H. Alex Choi, MD, have built since the start of the pandemic.
“We’re a good fit to be on the front lines of coronavirus research because in addition to being neurologists, we’re also intensivists,” said Choi, associate professor and vice chair ad interim for neuro critical care with McGovern Medical School, and a neurologist at UTHealth Neurosciences. “We’re interested in how systemic changes like sepsis and respiratory failure impact long-term cognitive functioning. We have established a prospective longitudinal study of COVID patients to understand how severe systemic inflammation can cause brain injury and long-term symptoms. We need to be part of the solution and understand how coronavirus affects patients long-term.” Choi is also the director of neurocritical care for Memorial Hermann Health System and director of the neuroscience intensive care unit at Memorial Hermann-TMC.
For more information about the PRANA Phase II study, call 713-500-UTHN (8846) or visit clinicaltrials.gov.