Descrizione del progetto
Trovare un equilibrio nel trattamento della carenza di insulina
La carenza di insulina è una condizione potenzialmente letale causata dalla perdita delle cellule β pancreatiche. Se non trattata, la carenza di insulina è una malattia catabolica caratterizzata dall’iperglicemia. Oltre all’aumento dei livelli di glucosio in circolazione, la perdita di cellule β conduce ad altre diverse complicazioni, anch’esse potenzialmente letali (iperchetonemia e chetoacidosi gravi). È dunque importante sviluppare strategie per il trattamento della carenza di insulina che migliorino l’iperglicemia, riducendo al contempo i rischi di altri difetti causati da questa malattia. I pazienti sottoposti alla terapia di insulina sono esposti a un rischio maggiore di sviluppo di insufficienza renale, cecità, danni ai nervi, infarto miocardico, ictus e ipoglicemia. L’obiettivo del progetto LifeWithoutInsulin, finanziato dall’UE, consiste nello sviluppare composizioni di trattamento che riducano la quantità del dosaggio di insulina e i rischi associati alla terapia di insulina.
Obiettivo
Tens of millions suffer from insulin deficiency (ID); a condition caused by pancreatic β-cell loss. If untreated, ID is a lethal catabolic disease characterized by hyperglycemia. Thus, the focus of ID research and drug development has been mainly on improving strategies to lower hyperglycemia without causing life-threatening hypoglycemia. However, in addition to increased circulating glucose level β-cell loss leads to several “other defects”, some of which (e.g. severe hyperketonemia and ketoacidosis) are life-threatening. Therefore, it is important to develop strategies that in addition to improve hyperglycemia can also rescue the “other defects” (e.g. increased ketogenesis) caused by ID. For example, we have recently published results underscoring the importance of ameliorating hyperglycemia and the “other defects”. Indeed, our data indicate that despite the presence of slightly improved hyperglycemia a normalization of hyperketonemia and hypertriglyceridemia is associated with a significant extension in lifespan of mice with β-cell loss (https://www.nature.com/articles/s41467-019-11498-x). Untreated ID rapidly leads to death. However, since insulin was discovered in the early 1920s, ID has been treated with insulin therapy; an approach that converted this lethal disease into one a person can live with. Yet, insulin therapy is unsatisfactory. Indeed, ID subjects have higher risks for developing kidney failure, blindness, nerve damage, heart attack, stroke, and hypoglycemia. Some of these defects are favored by insulin therapy itself. Our goal is to diminishing the amount of insulin dosage and hence reducing the risks associated with insulin therapy (e.g. life-threatening hypoglycemia). The present application aims at providing a composition for improving the treatment of ID. If successful, we will be able to commercialize our composition and improve therapy in millions suffering from ID.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotIstituzione ospitante
1211 Geneve
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