Stem Cell Treatment Seen to Benefit Lupus Patients in Phase 1 Trial, New Study Opening

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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A single infusion of mesenchymal stem cells (MSCs) — those that make cells of the cartilage, bone, and fat — decreased the number of auto-reactive immune cells in difficult-to-treat systemic lupus erythematosus (SLE) patients, a Phase 1 trial reports.

A Phase 2 study of this treatment is now opening in the U.S. and starting to recruiting eligible adults with lupus, ages 18 to 65.

Phase 1 findings were presented last month during the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) 2018 Annual Meeting in Chicago. The poster was tiled, “Marked Immune Cell Subset Changes in Refractory Lupus Patients in a Phase I Trial of Allogenic Mesenchymal Stem Cells.

MSCs, a type of stem cell able to differentiate into bone, cartilage, connective tissue, muscle, and fat cells has shown promise as a potential therapy for lupus patients who fail to respond to conventional therapies.

The cells can be obtained from the umbilical cord, bone marrow, adipose tissue, muscle, and the lungs.

Researchers at the Medical University of South Carolina (MUSC) conducted a Phase 1 clinical trial to investigate the effects of umbilical cord-derived MSCs in six patients with hard-to treat, refractory SLE. Each patient received a single injection of one million cells per kg.

Researchers measured how the infusion affected the patients’ immune system, focusing on subsets of immune cells with key functions in lupus.

Among T-cells, researchers examined regulatory T-cells (Tregs) — which dampen the activity of other immune cells — and helper T-cells, important mediators of autoantibody production by B-cells in lupus patients.

Among B-cells, the researchers measured the levels of non-reactive B cells and abnormal memory B-cells, which are relatively rare in healthy subjects but increased in SLE patients and associated with higher disease activity.

At 24 weeks post-treatment, the MSC infusion significantly reduced the amount of abnormal memory B-cells and increased non-reactive B-cells compared to levels recorded at study start (baseline) in four of the six patients. In two patients, the therapy was also associated with an increase in Tregs, but that rise was modest compared to changes in B-cells.

In a previous study, the MUSC researchers identified two proteins, the glycoprotein-A repetitions predominant (GARP) and the transforming growth factor (TGF)-beta, as key regulators of B-cell activity.

GARP is a cell surface receptor for TGF-beta and the interaction between both proteins was shown to regulate the activity of B-cells and prevent autoimmunity. GARP is highly expressed on MSCs and the levels of GARP and TGF-beta were significantly increased in patients’ blood following the infusion of MSCs.

Overall, these results support the clinical benefits of MSCs in hard-to-treat lupus.

The researchers have since launched a double-blind and placebo-controlled Phase 2 trial (NCT02633163) to evaluate the efficacy and safety of MSCs, given in combination with standard of care, in 81 adults with SLE.

The trial, currently recruiting, is taking place seven locations in six U.S. states, and enrollment information is available here.

Lupus patients will be randomized to one of two doses of MSCs — a low dose of one million cells or a high dose of five million cells — or to a placebo, each delivered a single time into the blood.

The trial aims to assess if patients treated with MSCs respond better than those given a placebo infusion plus standard of care.

Responders are defined as patients who experience a four-point or higher reduction in the Systemic Lupus Erythematosus Disease Activity Index score (SLEDAI), and receiving corticosteroids at a dose of 10 mg a day or less.

Additional measures include frequency of disease flares, accumulation of new damage, and changes in health-related quality of life, fatigue, pain, and depression.