Children’s Hospital of Philadelphia Receives Grant for Research in Mitochondrial Space

To advance vital mitochondrial medicine research and help decode the COVID-19 pandemic puzzle, Children’s Hospital of Philadelphia (CHOP) has received more than $2.3 million from the Bill & Melinda Gates Foundation.

As health officials monitor local and global COVID-19 infections, a critical question has surfaced – why are certain individuals and populations more severely affected by the SARS-CoV-2 virus – which causes COVID-19 – than others? To address this question and the resulting unprecedented demands being pressed on global medical institutions, the Center for Mitochondrial and Epigenomic Medicine (CMEM) at CHOP is determining if mitochondrial variation is an important factor in determining why certain patients have more severe symptoms to SARS-CoV-2 infection.

“Our mitochondrial studies have demonstrated that SARS-CoV-2 has a powerful adverse effect on patients’ mitochondrial function,” said Dr. Douglas Wallace, geneticist, evolutionary biologist and director of the CMEM at CHOP. “The genes of the DNA within the mitochondria, the mtDNA, are vitally important in cellular energy production and differ in sequence between individuals as well as people of different global ancestries. Therefore, we are investigating the role of mtDNA variation in determining the severity of COVID-19 symptoms.”

“With this transformative grant from the Gates Foundation we hope to not only determine the importance of mtDNA variation in COVID-19 severity, but also to identify new approaches for mitigating the adverse impact of COVID-19,” Wallace explained.

The CMEM focuses on understanding and potentially treating a broad spectrum of diseases by focusing on mitochondria, the “batteries” of our cells. The genes for generating mitochondria are dispersed across both the nuclear DNA and the mtDNA. CMEM is studying alterations in the mitochondrial genes in diseases as diverse as neuropsychiatric disorders from autism to Alzheimer’s disease, blindness, heart and muscle disease, diabetes and obesity, as well as SARS-CoV-2 infection.

Since the beginning of the pandemic, the CMEM team, in conjunction with the international COV-IRT consortium, have demonstrated that SARS-CoV-2 has a striking adverse effect on mitochondrial gene expression and function. CMEM investigators will now determine if mtDNA variation contributes to individual COVID-19 sensitivity.

“Based on current evidence, we have hypothesized that individuals with more energetically efficient mtDNAs, such as those from sub-Saharan Africa, may be less susceptible to SARS-CoV-2 mitochondrial inhibition and more resistant to COVID-19 pathology,” Dr. Wallace added. “The Gates Foundation funding will make testing this hypothesis possible.”