$Subvención de 1,6 millones de dólares de CIRM respalda un posible tratamiento para la diabetes

25 de septiembre de 2018

$Subvención de 1,6 millones de dólares de CIRM respalda un posible tratamiento para la diabetes

Salk scientists awarded translational grant for stem-cell-based therapy

25 de septiembre de 2018

LA JOLLA—Aproximadamente 1.25 millones de estadounidenses viven con diabetes tipo 1 (DT1), con 40,000 personas adicionales diagnosticadas cada año. La DT1 es una enfermedad autoinmune que destruye las células de los islotes pancreáticos que producen insulina. La insulina es una hormona que permite que el azúcar (glucosa) entre en las células para producir energía. Sin insulina, el azúcar en la sangre se acumula, causando efectos secundarios tóxicos. A pesar de la investigación activa, la DT1 no tiene cura. Si bien existen tratamientos, incluidas inyecciones diarias de insulina, el manejo de la enfermedad sigue siendo un desafío, y la DT1 mal controlada puede provocar ceguera, insuficiencia orgánica y otros problemas de salud.

Replacement therapies for beta cells (the cells that produce insulin in the islet) have been proposed as a game changer for T1D patients, potentially freeing diabetics from the daily burden of constantly managing their disease. There are two main challenges to transplanting insulin-producing islet cells: the shortage of transplantable cells and the underlying autoimmune response that destroyed the patient’s own islets.

Ronald Evans, a professor in Salk’s Gene Expression Laboratory and a Howard Hughes Medical Institute Investigator, believes that the development of immune tolerant human islet-like organoids, or HILOs for short, may be a solution. He’s not alone. The California Institute for Regenerative Medicine (CIRM) recently approved a $1.6 million grant to help bring Evans’ HILOs to patients with diabetes.

“We are excited that CIRM has elected to support our work,” says Evans. “Transplanted islet cells have the potential to dramatically improve the quality of life for people with type 1 diabetes, but we need to overcome the shortage of transplantable cells, and we need to manage the autoimmune response. We believe HILOs will do both.”

HILOs build upon a breakthrough Metabolismo celular paper published in 2016, which identified the secret switch (ERRγ) to generating mature functional islet cells; that is, cells that secrete insulin when they sense high sugar levels. HILOs are generated from pluripotent stem cells (which have the potential to become any tissue) and can be grown in large numbers, potentially solving the transplant shortage. These organoids contain a variety of cells, as well as a blood supply, to recapitulate normal islet cell function. In addition, early animal studies have shown HILOs are highly functional, secreting insulin in response to glucose.

“Our engineered functional human islet-like organoids are designed to circumvent the shortage of donor islets,” says Salk Research Associate Zong Wei, a member of the HILO project team. Salk Staff Scientist Eiji Yoshihara, a leading member of the HILO project team, notes, “In preclinical testing, our HILOs can immediately restore glucose homeostasis (balance) upon transplantation into T1D mice.”

The project was funded under CIRM’s Discovery Quest Program, which invests in research that can be rapidly translated into treatments. The team will use these funds to develop a safe and efficient protocol to scale up HILO production to eliminate islet cell shortages. From a therapeutic perspective, HILOs could provide the complete package: easily transplantable organoids that produce insulin, resist immune attack and can be grown in sufficient numbers.

“In addition to developing safe effective HILOs, we now have a way of cloaking the cells from the immune system, and thereby avoiding the autoimmune response that could destroy the implanted cells,” says Senior Staff Scientist Michael Downes, a senior member of the HILO team. “This is an exciting time. Although it is early days, the funding from CIRM will help develop HILOs to improve the quality of patient lives.”