Diabetic Nephropathy

MPC-300-IV is being developed for the treatment of diabetic complications, including diabetic kidney disease known as diabetic nephropathy.

Disease Indication and Patient Population

In type 2 diabetes patients there is an aberrant activation of the immune system associated with inflammation of various organs, including kidney, liver and fat tissues. This results in resistance to the effects of insulin in the fat tissues, and poor glucose control. Inflammation in the kidneys results in diabetic nephropathy.

While current anti-diabetic agents are effective in improving glucose control, they are not effective in preventing the renal complications in type 2 diabetes, which affect up to 40 to 50% people with type 2 diabetes1.

Diabetic nephropathy is the single leading cause of end-stage renal disease (ESRD), accounting for nearly half of all ESRD cases in the United States where there was an estimated 1.96 million2 cases of moderate to severe diabetic nephropathy in 2013. The current standard of care for diabetic nephropathy (renin-angiotensin system inhibition with angiotensin converting enzyme inhibitors of angiotensin II receptor blockers) only slows the rate of progression to kidney failure by 16-25%, leaving a large residual risk for ESRD.3

For patients with ESRD, the only treatment option is renal replacement (dialysis or kidney transplantation) which incurs high medical costs and substantial disruptions to a normal lifestyle. Due to a severe shortage of kidneys, in 2012 approximately 92,000 persons in the United States died while on the transplant list4. For those on dialysis, the mortality rate is high with an approximately 40% fatality rate within two years after initiation of dialysis5.

To the extent MPC-300-IV can be shown to be effective in this population, additional applications would be possible for the over 20 million people in the United States who are estimated to have chronic kidney disease.


MPC-300-IV is a tier 1 product candidate, consisting of up to 300 million mesenchymal precursor cells (MPCs) delivered intravenously to target the end-organ complications of type 2 diabetes, including diabetic nephropathy.

Mechanism of Action

The diverse and potent anti-inflammatory properties of MPCs are the foundation for their usefulness in diseases such as the end organ complications of diabetes, where monocytes, macrophages and activated pro-inflammatory T cells play contribute to the disease pathogenesis through activation of multiple pro-inflammatory cytokine pathways.

More specifically, MPC-300-IV was designed for intravenous delivery to treat systemic and localized conditions of excessive inflammation, where MPCs can counteract inflammatory processes by down- regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of anti-inflammatory cells to involved tissues.

MPCs produce immunomodulatory biomolecules such as prostaglandin E2, or PGE2 and indoleamine2, 3-dioxygenase, or IDO, in response to activation by pro-inflammatory cytokines such as tumor necrosis factor-alpha, or TNF-alpha; interleukin-1, or IL-1; interleukin-6, or IL-6; interleukin-17, or IL-17. These MPC-released biomolecules act along multiple pathways, such as polarizing pro-inflammatory M1 monocytes to anti- inflammatory M2 monocytes, neutralizing harmful macrophages, and switching activated T helper cells 1 and 17, or Th1 and Th17, respectively, to Th2 cells and FOXP3 T regulatory cells.

Results from a Phase 2 randomized controlled trial in patients with diabetic nephropathy showed a reduction in IL-6 levels which suggests that the mechanism of action of MPCs may involve reduction of pro-inflammatory M1 monocyte cytokines in the diabetic kidney.

Clinical Trials

Phase 2 Trial

MPC-300-IV was evaluated in a double-blind, randomized, placebo-controlled, dose escalating Phase 2 trial of 30 patients with type 2 diabetes and moderate to severe renal impairment, stage 3b-4 chronic kidney disease (CKD), who were already on a stable regimen of the standard of care therapy for diabetic nephropathy (renin-angiotensin system inhibition with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers).

Patients received a single infusion of 150 million MPCs, 300 million MPCs, or saline control. The objectives of the trial were to evaluate safety and to explore potential efficacy signals of MPC treatment on renal function. The pre-specified primary efficacy endpoint was to evaluate effects of MPC treatment relative to placebo on renal functional decline at 12 weeks, as defined by change in glomerular filtration rate (GFR) measured both by direct isotope scan and by serum-creatinine based estimation, and then for an additional 48 weeks of follow-up. The primary efficacy endpoint of decline or change in GFR was in line with the 2012 joint workshop held by the United States Food and Drug Administration and the National Kidney Foundation which recommended that time to 30%-40% decline in GFR is an acceptable primary endpoint for evaluating potential benefits of new therapies for this patient population.6

The results were presented at the late-breaking scientific sessions of the 75th annual meeting of the American Diabetes Association in June 2015 and published in EBioMedicine in October 2016. Click here for more information.

Find out more about this Phase 2 trial 


1Decision Resources Chronic Kidney Disease October 2013

2USRDS, Annual Data Report, 2014

3Lambers-Heerspink HJ et al. Diabet Med 2007;24(11):1290-1295

4USRDS, Annual Data Report 2014

5Robinson BM et al Kidney Int 2014; 65. Epub 2013 Jun 26

6Levey et al. GFR decline as an endpoint in clinical trials for CKD. American Journal of Kidney Disease 2014:64(6):821-835)