The oldest approach to the definitive treatment of type 1 diabetes mellitus (T1D), instead of the classic intensive insulin therapy, since 1982, has been pancreatic islet transplantation, extracted from the pancreas of human donors and transplanted into patients with the disease, under pharmacological immunosuppression of the recipients to avoid immune rejection, or as done first in the world, by our Endocrine and Biohybrid Organ Cellular Transplantation Laboratory at the University of Perugia, protecting the islets in special microcapsules to allow engraftment, without resorting to generalized immunosuppressive therapy burdened with multiple side effects.
However, the success of this approach has been globally rather limited in terms of actual numbers, both of T1D patients who could suspend insulin therapy after transplantation, sometimes “pro tempore,” and of international centers where such success have been achieved, which can be counted on the fingers. Another problem has always been represented by the costs of the procedure and its possible reimbursement by Health Organizations, in fact, so far limited to Canada, France, and Australia.
A recent step forward (July 2023) in this regard, has come from the United States of America, where the Food and Drug Administration (FDA) has officially approved the use of human pancreatic islet transplantation in T1D patients undergoing pharmacological immunosuppression, granting it the status of “drug” (thus legitimizing a procedure confined to pure clinical phase I-II experimentation). This “product,” officially named LANTIDRA (donislecell), is recommended for T1D patients who, despite following intensive insulin therapy regimens, are unable to control blood sugar, with elevated levels of glycated hemoglobin, and frequent episodes of severe hypoglycemia due to reduced ability to recognize classic symptoms of sugar drop (“hypoglycemia unawareness”), both indicative of poorly controlled diabetes. Obviously, poorly controlled diabetes causes various complications affecting important organs and systems such as the eyes, kidneys, cardiovascular system, and nervous system. Many of these are associated with highly disabling and sometimes lethal effects, also resulting in a huge financial burden on the National Health System.
LANTIDRA is a product that has come a long way, developed after 20 years of intense work by CellTrans Inc., a spin-off of the University of Illinois in Chicago (UIC). It was the UIC that launched a research program in the early 2000s, the Chicago Project for the refinement of the separation and purification of human pancreatic islets, in which our Laboratory in Perugia was actively involved, with numerous trips to Chicago for research in the exchange of human pancreatic islets between Chicago and Perugia.
Lantidra is still comprised of Islets of Langerhans, extracted from the pancreas of human donors to be transplanted by infusion into the portal vein reaching the liver, under pharmacological immunosuppression of the recipients. However, it is the first time that the US FDA has officially approved it, as mentioned above, as a “drug” administerable to those classes of T1D patients mentioned above. It is a product that fully meets the safety and efficacy requirements never before recognized by the FDA in similar products. The “drug” is administered in a single infusion after transcutaneous cannulation of the portal vein under local anesthesia, and the procedure can be repeated, depending on the metabolic response of the patient undergoing the treatment.
The safety and efficacy criteria of the drug, which led to its approval, have been well demonstrated by two clinical studies conducted in 30 patients, with the aforementioned clinical characteristics, who were subjected to one and up to three infusions of pancreatic islets. Some side effects have been observed as a result of immunosuppressive therapy, which is essential for maintaining viability of the implanted islets, but without significant compomission of health conditions of the treated patients.
In summary, the benefits associated with the use of Lantidra far outweigh the risks associated with the procedure in patients with poorly controlled and uncontrollable diabetes by common optimized insulin therapy regimens, and the strengths of the new drug can be summarized as follows:
1. Islet transplantation is able to restore good glycemic-metabolic control in most treated patients, with beneficial effects that can persist for years;
2. Islet transplantation improves quality of life of the treated patients by allowing them to engage in activities previously interdicted;
3. Islet transplantation can slow down or induce the remission of many debilitating secondary complications of type 1 diabetes;
4. Even if the transplantation function were partial, transplantation still leads to an improvement in glycemic control, reduced consumption of exogenous insulin, and improvement in the patient’s quality of life;
5. The use of LANTIDRA is generally safe, as the implant procedure is minimally invasive;
6. Most of the risks associated with islet transplantation depend on the use of immunosuppressive drugs, already approved for anti-rejection treatment of organ transplants, based on their favorable risk/benefit ratio;
7. Unstable (brittle) type 1 diabetes is a debilitating disease that is not controllable with common insulin therapy protocols, and in these instances, islet transplantation remains an effective therapeutic option;
8. More than 20 years of experience with the procedure have demonstrated its safety and efficacy in patients with brittle type 1 diabetes;
9. The adverse effects of pharmacological immunosuppression can be avoided by the use of microcapsules, applied for decades, even in clinics, by our Endocrine and Biohybrid Organ Cellular Transplantation Laboratory in Perugia.