Diabetes is a disease in which the body does not produce enough or is unable to respond to insulin, a hormone secreted by the pancreatic β-cells (Langerhans islet cells) that turns glucose into energy.
In greater detail, diabetes distinguishes into Type 1 diabetes, in which Langerhans islet cells do not produce insulin and which is in most cases of autoimmune origin, and Type 2 diabetes, a condition due to a defective responsiveness of the cells to insulin, usually combined with a reduced insulin secretion.
The therapy of Type 1 diabetes consists in the administration of artificial insulin via subcutaneous injections combined with a careful monitoring of blood glucose levels. The therapy of Type 2 diabetes in its initial stages consists in the administration of oral medicaments that improve insulin resistance, decrease glucose release by the liver and stimulate the increase of insulin secretion, but at later stages it requires also insulin administration.
Since both Type 1 and Type 2 diabetes are at least partially inherited, subjects with relatives suffering from this pathology have a certain risk of developing diabetes.
Furthermore, a series of predictive markers have been identified that are able to foretell the onset of diabetes, in particular Type 1 diabetes (Curr Diabetes Rev, 208, May 4(2), 110-121; Autoimmune Rev 2006 July, 5(6), 424-428). It is therefore possible to identify at low cost and with easy procedures individuals with high risk of developing the disease.
A number of attempts to control and/or delay the onset of diabetes in individuals at risk have been made; however, these require the use of therapies with too a high costs/benefits ratio. Therefore, at present, in spite of the availability of tools able to predict this disease, there is no adequate pharmacological treatment able to prevent or at least delay its onset.
The only strategy that can be adopted in subjects at risk is periodic monitoring of glycaemia and a healthy lifestyle, including control of body weight, physical exercise and adequate dietary regimen. However, this has a very limited efficacy.
Thus, there is a long felt need for medicaments for the prevention of diabetes.
EP 1 123 276 discloses N-(2-aryl-propionyl)-sulfonamides, among them R(−)-2-[(4-isobutylphenyl)propionyl]-methanesulfonamide (I), and their pharmaceutically acceptable salts, for use as inhibitors of neutrophil chemotaxis and degranulation induced by IL-8, in particular for use in the treatment of pathologies like psoriasis, rheumatoid arthritis, ulcerative colitis, acute respiratory insufficiency (ARDS), idiopathic fibrosis and glomerulonephritis.
EP 1 355 641 discloses the use of R(−)-2-[(4-isobutylphenyl)propionyl]-methanesulfonamide and pharmaceutically acceptable salts thereof, in particular its lysine salt, in the prevention and treatment of ischemia/reperfusion injury of transplanted organs and of functional injury resulting from rejection reactions after solid organ transplantation, in particular kidneys, which need to be retrieved from a donor and stored before transplantation. Such injuries are deemed to be responsible for delayed graft function, which makes dialysis necessary in case of renal transplantation.
EP 1 579 859 discloses the use of N-(2-aryl-propionyl)-sulfonamides, among them R(−)-2-[(4-isobutylphenyl)propionyl]-methanesulfonamide and its lysine salt, for the preparation of medicaments for the treatment of spinal cord injury.
USPTO Backgrounds
USPTO Backgrounds