Acute Respiratory Distress Syndrome (ARDS), which can be caused by β-coronaviruses such as COVID-19, involves inflammation of the lungs and can also result from viral infections affecting the brain stem respiratory center (BSRC). Standard therapies targeting viral infection or inflammation may not adequately address the neurological aspect of ARDS, as current treatment approaches, including drug repurposing and convalescent plasma therapy, do not sufficiently target these neurological issues, highlighting an urgent need for therapeutic strategies that address both viral spread and associated neuronal damage to enhance patient survival and recovery.
To treat viral respiratory disorders such as SARS-CoV-2, our researchers advocate combination therapy of pioglitazone (PG) and intranasally administered mesenchymal stem cells (MSCs). PG's anti-inflammatory effects via PPAR-γ (FDA-approved for the treatment of diabetes) activation create a conducive environment for MSCs to promote neuro-regeneration, proven effective in traumatic brain injury models. Additionally, PG's antiviral properties against RNA viruses and recent successes with ACE2- MSC transplantation in COVID-19 patients highlight potential benefits for mitigating disease severity and improving outcomes, especially in critically ill individuals with heightened inflammatory responses.
The diagram illustrates that PG demonstrates anti-inflammatory properties. Treatment with PG led to a notable decrease in TNF a and NF-kB p50 subunit expression in LPS-stimulated HEK293 cells. The diagram depicts the relative fold change in RNA expression compared to the control culture. Veh: Vehicle; *p<0.05, **p<0.005.