The prevalence in the US is approximately 1 in 300 persons under the age of 20. The incidence worldwide increases by 2% to 5% per year. The therapy of T1D is a major burden to health care in the US. Currently, the therapy of T1D consists of treatment with insulin. Despite significantly improved options for glucose control (glucose sensors, insulin pumps), mortality and morbidity are significantly increased in patients with T1D. Potential therapeutic options include treatment with alpha-1 antitrypsin (AAT) and/or mesenchymal stem cells (MSC).

In 4 clinical trials (Park et al Medicina 2001), therapy with AAT was shown to be safe and without side effects. Patients experienced an improvement in beta cell function and a reduction in Il-1ß. Ma et al (J Clin Med 2019) showed in the NOD mouse model that administration of an rAAV vector can prevent the development of T1D. Lu et al (Stem Cell Research & Therapy 2021) performed a study in 27 patients with T1D. Patients received 2 infusions (10⁶ cells per kg/KG 0 and 3 months) of allogeneic MSC. 40.7% of patients treated with MSC reached the primary endpoint with improvement of postprandial C-peptide. 3 patients were still completely without insulin therapy after 12 months. The MSC therapy was well tolerated.

We have a patented genetically modified mesenchymal stem cell expressing AAT (MSC‑AAT). In a preclinical model, we were able to show that MSC-AAT is more effective than naïve MSCs in preventing the development of T1D.

Animals receiving 5x10⁴ MSC-AAT showed no T1D, in contrast to 50% of the animals in the control group and 10% of the animals with the highest dose of naïve MSC.

The MSC-AAT we developed seem to be a promising therapy for patients with new-onset type 1 diabetes.