Mesoblast Ltd has announced the results of their clinical trial in type 2 diabetics at the annual meeting of the American Diabetes Association.
Mesoblast has developed a proprietary adult stem cell they call a mesenchymal precursor cell or MPC, which they are attempting show can be used as an “off the shelf” medical product. MPCs seem to act like immature mesenchymal stem cells that can modulate the immune response and have greater flexibility.
In this trial, Mesoblast was banking of the ability of administered MPCs to suppress inflammation. Type 2 diabetes results from an insensitivity of tissues to secreted insulin. Consequently, cells do not receive enough of the insulin signal to take up sugar and make protein, glycogen, and fat. Another prominent feature of type 2 diabetes is chronic, low-level inflammation, which is largely due to the chronically high blood glucose concentrations that damages cells, blood vessels, nerves, and connective tissue. By treating type 2 diabetics with MPCs, Mesoblast was hoping to ascertain the ability of MPCs to quell chronic inflammation.
The trial was conducted across 18 sites in the US. 61 patients with type 2 diabetes received either one intravenous infusion of 0.3, 1.0 or 2.0 millions MPCs per kilogram body weight over 12 weeks. One group of patients were given a placebo. Patients had suffered from diabetes an average of 10 years and had poor control with the drug metformin (Glucophage), which is one of the most widely-used drugs for type 2 diabetes.
The results were largely positive:
When it comes to safety, there were no safety issues observed during the 12-week study period. The MPC cell infusions were well tolerated (with a maximal dose of 246 million cells). With regard to efficacy, there were dose-dependent improvement in glycemic control as evidenced by a decrease at all time points after week 1 in hemoglobin A1c (HbA1c) in MPC- treated patients compared with an increase in HbA1c in placebo treated subjects. HbA1c is a blood test that determines how much damage the high sugar levels are doing to the body. The test uses the blood protein hemoglobin to assess the damage that high glucose levels are doing to the rest of the body. In this clinical trial, significant reductions in HbA1c were observed after 8 weeks in the 2 M/kg MPC group compared to placebo (p<0.05) which was sustained through 12 weeks. The reduction in HbA1c was most pronounced in subjects with baseline HbA1c ≥ 8% (i.e. those patients with relatively poorer glucose control).
Fasting insulin levels were reduced in the 1 million and 2 million/kg groups compared to placebo (P<0.05), and reduced levels of inflammatory cytokines TNF-alpha and IL-6 (which are made at high levels during inflammation) were observed at 12 weeks in MPC groups compared to placebo.
The scientists and physicians involved in this clinical trial concluded there was sufficient evidence to support further evaluation into the use of MPCs in the treatment of type 2 diabetes and its complications. They also thought that there were grounds for exploring other therapeutic venues in which MPCs might prove useful.
Mesoblast Chief Executive Silviu Itescu said: “We are very pleased with these results which are consistent with an immunomodulatory mechanism by which our MPCs may have glucose-lowering effects in patients with type 2 diabetes. We are evaluating whether similar effects may be seen with the use of MPCs in the treatment of kidney disease and other complications of type 2 diabetes.”
While it is improbable in the extreme that this one-time treatment will improve the long-term clinical outcomes of diabetics, it is possible that repeated treatments will provide better Glycemic control for poorly controlled diabetics, and that these repeated treatments will produce long-term improvements in the health of these patients.