Stem Cell Therapy Considered Safe and Eases Symptoms in Adults With RDEB, Phase 1/2 Trial Shows

Using mesenchymal stem cells to treat adults with recessive dystrophic epidermolysis bullosa (RDEB) appears to be safe and may ease symptoms such as itching for at least two months, a Phase 1/2 clinical trial shows.

The results were described in the study “A Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa,” which was published in the Journal of the American Academy of Dermatology.

RDEB is caused by mutations in the COL7A1 gene, which codes for the collagen type 7 protein. These alterations impair protein function, which ultimately results in the symptoms (e.g. blistering) that characterize the disease.

Cell-based therapies have shown promise in RDEB. Among these are mesenchymal stem cells (MSCs), a type of cell with the capacity to self-renew and differentiate into multiple types of cells, such as muscle and fat cells.

In RDEB, MSCs are thought to work by secreting signaling molecules that promote tissue growth and wound repair.

In the study, a team at King’s College London and their collaborators used allogenic MSCs, which involves taking stem cells from the bone marrow of a donor and injecting them directly into the bloodstream of the RDEB patient.

This type of therapy has been studied in clinical trials and resulted in promising outcomes. However, of the 24 RDEB patients treated in these trials, all but one were children.

As such, the team conducted a Phase 1/2 clinical trial (NCT02323789) to evaluate intravenous MSC injection in 10 adults with RDEB (age range 26–55 years).

Participants were treated with two MSC injections comprising 2 million to 4 million cells per kilogram of body weight. The injections were given two weeks apart. One participant withdrew after the first injection due to kidney problems that had started prior to the trial. The remaining nine participants received both injections.

The trial’s primary aim was to assess the safety of this treatment strategy. No serious adverse events were reported. Three participants collectively reported nine adverse events, none of which were deemed related to treatment.

Two participants developed squamous cell carcinoma (SCC) — a type of cancer common among people with RDEB — about six to seven months after the injections.

Total blister count over the entire body decreased at days 28 and 60 (two months) following treatment. Itch, assessed with the Leuven Itch Scale, showed significant reductions in frequency up to six months after treatment. Itch severity also eased at one and two months, but returned to baseline levels at six months.

Quality of life, as measured with the Quality of Life in EB scale, also improved up to two months after treatment.

Laboratory measurements were generally unchanged following MSC injection. The exception was a biomarker of inflammation called High Mobility Group Box-1 (HMGB-1), whose blood levels were significantly lower four weeks and two months after the injections.

“Overall, the use of intravenous MSCs in adults with RDEB appears to be safe, but with the caveat that other similar clinical trials should carefully monitor the potential complication of promoting SCC development or progression,” the researchers wrote.

“Although the primary objective was safety, we also noted variable and transient [temporary] improvements, maximal around days 28 and 60 post infusion of MSCs, particularly in the reduction of pruritus [itching],” they added.