Anti-inflammatory exosomes could have a place in treating acute kidney injury (AKI) caused by ischemia repercussion injury (IRI), according to a study done by ILIAS Biologics, Inc. in collaboration with Yonsei University of Seoul, South Korea.
ILIAS Research team and Yonsei University research team, led by professor of internal medicine Tae-Hyun Yoo and professor of oral pathology Jong In Yook, published the study result in the official journal of the International Society of Nephrology, Kidney International(Link).
ILIAS Biologics, Inc. secured its third proof of concept (POC), demonstrating the therapeutic efficacy of their anti-inflammatory exosomes with this successful result in IRI-AKI. This study result comes just after its second POC in the field of preterm birth, published in Science Advances last January. With its platform technology EXPLOR® (Exosomes engineering for Protein Loading via Optically Reversible protein-protein interaction), ILIAS has demonstrated the therapeutic applicability of its anti-inflammatory exosomes in multiple inflammation-related therapeutic areas, including sepsis, preterm birth, and IRI-AKI.
AKI affects approximately one million people annually worldwide. It is characterized as a rapid decline in kidney function, and multiple conditions such as acute tubular necrosis and interstitial nephritis can cause AKI. IRI is a major cause of AKI, often occurring in the aftermath of heart valve surgery. Severe AKI can result in permanent damage and, therefore, dysfunction of the kidney.
"Even though AKI is a relatively common disease capable of progressing to permanent kidney dysfunction and threatening the lives of many patients, there has been no drug with proven clinical efficacy and safety for its treatment. Therefore, this study suggests that exosome therapeutics could be promising clinical intervention for the prevention of IRI-AKI occurring post-heart surgery," says professor Tae-Hyun Yoo.
Using ILIAS' unique exosome therapeutics platform technology EXPLOR®, the research team successfully generated NF-κB inhibiting anti-inflammatory exosomes by loading super-repressor of IκBα (srIκB), an engineered dominant active form of NF-κB inhibiting protein IκBα with a prolonged half-life, into exosomes. Systemic administration of anti-inflammatory exosomes into preclinical IRI-AKI mouse models significantly lowered AKI-related biomarker levels in the blood, i.e., BUN(blood urea nitrogen), creatine, and NGAL(Neutrophil Gelatinase-associated Lipocalin).
This treatment also decreased NF-κB activation, expression of adhesion molecules, apoptosis, and release of pro-inflammatory cytokines. Intravital imaging revealed that neutrophils and macrophages were the principal cells that uptook the exosomes after in vivo administration.
The results suggest that intracellular delivery of srIκB to immune cells in the kidney can ameliorate IRI-AKI by reducing excessive inflammation, thus pointing to ILIAS' exosomes as the next potential novel IRI-AKI therapeutic.
"Therapeutic exosomes with EXPLOR® technology have successfully demonstrated its therapeutic potential in preclinical models representing multiple disease settings, including sepsis, preterm birth, and AKI. The results support that our engineered exosomes could be a game-changing novel therapeutics with minimal side effects for the treatment of inflammation-associated diseases that are at present incurable," said Chulhee Choi, CEO/CSO of ILIAS Biologics Inc. "We will also continue to deepen our therapeutic pipeline by developing first-in-class therapeutic exosomes for the treatment of other incurable diseases, as well as accelerating o...
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