Doctors Miguel Barajas, Enrique Andreu and Dr. Javier Escalada. PHOTO: Manuel Castells

A team of researchers at the Clínica Universidad de Navarra has initiated a phase I-II clinical trial essay with adult stem cells, obtained from the patient's own bone marrow, to treat autoimmune diabetes mellitus subject 1 (DM1A) in its most incipient stages. The treatment is based on the administration of mesenchymal cells, characterized by their ability to differentiate into different cell types and by their immune regulatory (immunomodulatory) action. The general goal of essay is based on trying to"stop the autoimmune aggression of the disease through treatment with this subject of stem cells", as described by Dr. Javier Escalada, researcher and manager of the Diabetes Unit of the Endocrinology Unit of the Endocrinologydepartment at Clínica Universidad de Navarra.

The essay will last for one year in its initial phase and it is estimated that it will take up to 3 years to obtain definitive results. The research has been promoted by CAIBER (Plataforma Española de Ensayos Clínicos), belonging to the Instituto de Salud Carlos III. The work has been financed by an ICI fund (research Independent Clinical Trial) of the Ministry of Health. It is a multicenter clinical essay , although the Clinic is the first hospital to launch it and is also the leader of the research.

"This project aims to carry out the first experience of translational clinical research from the results obtained with immunomodulatory cellular treatments in animal models of diabetes. For this reason, the same project, integrates a group of clinical specialists with another of researchers from area of Cell Therapy, dedicated to studying preclinical models of this disease, and another from the Clinical Biochemistry Service dedicated to the biology of mesenchymal stem cells", emphasizes the endocrinologist.

The disease and its increasing prevalence

Diabetes mellitus 1A is a disease of autoimmune origin characterized by the destruction of the beta cells of the pancreas, which generate insulin. The elimination of these cells is caused by a reaction of the immune system against its own pancreatic islets, Structures which contain the beta cells of the pancreas. As is known, insulin is the hormone responsible for facilitating the glucose present in the blood after food intake to penetrate into the cells and thus be used as energy source . Insulin is therefore also responsible for controlling blood glucose levels.

Diabetes mellitus 1 manifests itself at an early age and does not show symptoms until the disease presents the classic clinical picture characterized by excessive thirst, very abundant urine, weight loss and fatigue. Statistically it represents between 5 and 10% of all cases of diabetes mellitus. Its prevalence in Spain is between 12 and 20 cases per 100,000 inhabitants, although in recent years, due to causes that are still unknown, there has been an increasing trend in the incidence of this disease.

Conventional treatments and novelty of the essay

To date, the treatment of this subject diabetes is based on the administration of insulin, of which a greater supply is required as the disease progresses. subject Pancreatic islet transplantation is used to treat this type of diabetes, although this technique has the disadvantage of requiring immunosuppressive medication to prevent rejection, as well as the added problem of the shortage of donors needed to treat all patients suffering from DM1A.

"The novelty of our essay is the treatment of this subject of diabetes with the patient's own adult stem cells," warns the specialist. Conventional treatments of the disease based on insulin supply, "although they have undergone interesting developments with insulin analogues, continue to involve daily dependence on numerous injections that require constant intervention by the patient, for which an advanced diabetic Education is necessary".

No immunosuppression

The protocol proposed by the Clinic's team for the treatment of DM1A with adult mesenchymal stem cells, obtained from bone marrow, may constitute a new therapeutic procedure for diabetic patients. issue M oreover," he adds, "this strategy presents an additional advantage since it is possible to extract the mesenchymal cells from the patient's own bone marrow, expand them in vitro, to obtain a sufficient number of cells to allow us to carry out the transplant and implant them in the patient himself, without the need for immunosuppressive treatments".

According to Dr. Escalada, "the possibility of modifying the autoimmune attack with a cellular product from the patient himself would represent an enormous advance". For the specialist, this would mean "an important step forward in the search for curative treatments for the disease which is currently the main cause of end-stage renal failure and blindness in developed countries, as well as a major factor in expense healthcare".

Efficacy in 40% of NOD mice
 

Dr. Miguel Barajas observes the culture of adult mesenchymal stem cells under the microscope.

Photo: Manuel Castells

The launch of this clinical essay is based on the results obtained in a preclinical study by a team of researchers from the Clinic's Cell Therapy area , led by Dr. Felipe Prósper, with decades of experience in the development of treatments based on the use of adult stem cells for different diseases.

This Cell Therapy team recently conducted the study in NOD mice, a species genetically prone to develop autoimmune diabetes mellitus subject 1 (DM1A). " We observed that this disease, as we are already doing with other pathologies of autoimmune origin, could constitute a possible target to be treated with mesenchymal cells that could be beneficial due to their important immunomodulatory properties", says Dr. Miguel Barajas, specialist of area Cell Therapy of the Clinic and coordinator of this line of research on the cellular treatment of DM1A in model animal.

In the preclinical research they found that in 40% of the mice that were administered a single dose of mesenchymal cells the disease was halted, and in the cases in which the administration of these cells from other mice (heterologous) was repeated, the effectiveness occurred in more than 50% of the treated animals.

All the necessary cell processing is carried out at the Clinic thanks to the laboratory GMP (Good Manufacturing Practice or international standards of good practice) Cell Therapy facilities available at the hospital. The work at model animal counted with the participation of the laboratory of Immunology of the research center Applied Medicine (CIMA ) of the University of Navarra.

Inclusion criteria and methodology

The essay is aimed at patients with a recent diagnosis of DM1A, older than 18 years and younger than 45 years, who have been diagnosed with the disease up to 8 weeks before participating in the study. In addition, they must have detectable levels of C-peptide, indicative of insulin reserves, and positive antibodies against pancreatic beta cells.

The treatment applied during the essay will consist of the extraction of bone marrow by puncture of the iliac crest and the selection and culture of mesenchymal cells from this marrow at the Clinic's laboratory GMP for Cell Therapy to prepare a preparation that will be administered intravenously, initially in a single dose. "The complications associated with these procedures in the published series are exceptional, so we expect this to be a highly safe treatment," says the specialist.

Every three months a blood test will be performed in order to monitor and analyze the response obtained in each individual. Stimulus tests (oral administration of a nutritional preparation) will be performed and samples will be taken at each hospital of origin. The samples will be sent to Clínica Universidad de Navarra for processing, analysis and measurement of biochemical and immunological parameters.

"Given that to date no treatments for diabetes based on the use of autologous (the patient's own) mesenchymal cells have been described, the results obtained from this study will be of great scientific interest," agrees the specialist.

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