Novel Peptide Therapy to Halt the Progression of Chronic and Acute Kidney Disease

This invention is a therapeutic approach utilizing HMMR-inhibiting peptides and related nucleic acid molecules to target a key molecular driver of kidney disease. This therapy offers a promising and previously unrecognized mechanism to ameliorate kidney injury, demonstrating efficacy in the treatment and inhibition of both Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) progression.

Description

The core technology is based on the novel discovery that the Hyaluronan-Mediated Motility Receptor (HMMR) is a previously unrecognized driver of kidney disease progression, as its expression is markedly upregulated in human and experimental Chronic Kidney Disease (CKD) but virtually undetectable in healthy adult kidney tissue. This overexpression promotes key pathological processes, including tubular injury, interstitial fibrosis, and inflammation, by signaling through the ERK and mTOR pathways. The innovative aspect is the use of HMMR function-blocking peptides that directly disrupt the interaction between HMMR and hyaluronan (HA) at the cell surface. By inhibiting this receptor function, the peptides effectively suppress the harmful downstream signaling and markedly ameliorate kidney damage across models of both chronic and acute injury. The therapeutic agents include the inhibitory peptides themselves, or nucleic acid molecules (like inhibitory RNA or vectors) that encode or inhibit HMMR.

Applications

- Therapeutic treatment for Chronic Kidney Disease (CKD), including patients with diabetic nephropathy, lupus nephritis, and focal segmental glomerulosclerosis.
- Treatment and prevention of Acute Kidney Injury (AKI) stemming from acute causative events like sepsis, ischemia-reperfusion injury, or nephrotoxic drug exposure.
- Development of novel anti-fibrotic and anti-inflammatory drugs to inhibit maladaptive tissue remodeling in the kidney.
- Combination therapy to be administered alongside existing treatments for kidney disease, such as Renin-Angiotensin-Aldosterone System (RAAS) inhibitors.
- Diagnostic/Prognostic tools leveraging HMMR expression levels as a biomarker for kidney disease risk and progression.

Advantages

- Targets HMMR, a previously unrecognized molecular driver of kidney disease progression that is undetectable in normal adult kidneys.
- Demonstrates efficacy in treating and inhibiting both Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD).
- Attenuates renal fibrosis and actively mitigates tubular injury, key pathological hallmarks of progressive kidney disease.
- Suppresses renal inflammation by significantly reducing macrophage and T cell infiltration into the kidney.
- Works by disrupting HMMR-hyaluronan interactions and suppressing pro-pathogenic signaling via the ERK and mTOR pathways.

Invention Readiness

The technology has been successfully validated in preclinical animal models, demonstrating robust therapeutic efficacy in both a Chronic Kidney Disease (CKD) model (Unilateral Ureteral Obstruction) and an Acute Kidney Injury (AKI) model (cisplatin-induced nephrotoxicity). Extensive data confirms that the peptide treatment significantly ameliorates kidney injury, including reductions in tubular damage, fibrosis, and inflammation, while also inhibiting pathogenic ERK and mTOR signaling pathways. Future studies should focus on advanced toxicology, pharmacokinetics, and large animal models to support the translation of the peptide or nucleic acid therapy into first-in-human clinical trials.

IP Status

Patent Pending