Preclinical Studies Show MA-0217 Has Potential to Improve Mitochondria Activity, Kidney Function
Mitobridge’s investigative PPARδ modulator MA-0217 has been shown to improve mitochondria activity and kidney function in animal models of acute kidney injury.
The findings were the subject of two poster presentations titled, “Modulation of PPARδ with MTB-2 Post-Reperfusion Attenuates IR-Induced AKI Injury Biomarkers and Histopathology in Rats,” and “PPARδ Modulator MTB-2 Enhances FAO In Vitro and Attenuates Ischemia-Reperfusion-Induced Gene Expression Changes In Vivo 48 Hours and 14 Days Post AKI,” during the American Society of Nephrology Kidney Week 2017 Annual Meeting in New Orleans.
Mitochondria are essential for normal cell activity. When dysfunctional, they can trigger a variety of medical conditions, including acute conditions and chronic degenerative diseases. A better understanding of mitochondria dysfunction and finding ways to prevent it can represent an alternative therapeutic strategy for several diseases.
Mitobridge has been developing MA-0217, also known as MTB-2, a potent and highly selective regulator of the peroxisome proliferator-activated receptor (PPARδ), for the treatment of kidney diseases.
PPARδ is an important mediator of several mitochondria functions including fatty acid metabolism and energy production. Activation of this receptor will regulate mitochondria activity, and consequently impact overall cell and tissue responses.
Preclinical evaluation of MA-0217 in animal models of acute kidney injury demonstrated its therapeutic potential. Intravenous administration of the investigative drug for two days showed to reduce kidney tissue damage and improve filtration activity of the kidney, while it significantly reduced blood biomarkers of acute kidney injury.
In addition, MA-0217 was shown to improve mitochondria activity, as demonstrated by improved fatty acid oxidation as well as preservation of the levels of mitochondrial genes.
“These proof-of-concept data demonstrated that MA-0217 can enhance mitochondrial fatty acid oxidation in human kidney cells and restore kidney function in animal models of the disease,” Effie Tozzo, senior vice president of Translational Sciences at Mitobridge, said in a press release.
A compound similar to MA-0217 called MA-0204 also improved mitochondria activity and recovered renal function in severely obese, diabetic animals with chronic kidney disease. These data further demonstrate the therapeutic potential of PPARδ modulation, or regulation, and its positive impact on mitochondria function.
The results were also presented at the ASN Kidney Week in the poster presentation titled, “MA-0204 modulation of PPARδ promotes recovery after AKI in normal and aged proteinuric diabetic CKD Zsf1 rats by enhancing fatty acid oxidation in proximal tubular epithelial cells.”
Acute kidney injury “is a serious condition and there are no currently approved therapies to help manage patients,” said Bruce A. Molitoris, professor of medicine and director of the Indiana Center for Biological Microscopy at Indiana University. “MA-0217 may address the cellular injury, mitochondrial dysfunction and organ damage associated with AKI and represents an innovative option for this life-threatening condition.”
“The presented data are quite promising and I look forward to seeing the compound enter clinical development,” Molitoris added.