NephroDI Therapeutics is a pharmaceutical company that focuses on concentration disorders of the kidney. The initial clinical indication for its orally administered lead small molecule is for Nephrogenic Diabetes Insipidus in children, a pediatric orphan indication.
Nephrogenic Diabetes Insipidus (NDI) is a disease where patients produce extremely large amounts of dilute urine resulting from an inability of the kidney to respond to vasopressin. Congenital NDI in the pediatric population results primarily from mutations in the type 2 vasopressin receptor, which is located on the X chromosome. Congenital NDI has a profound impact on children. Since these children can produce up to 20 L of urine per day, they must drink 20 L of water per day to avoid dehydration. Children who suffer multiple episodes of severe dehydration often end up with mental retardation.
NDI should not be confused with diabetes mellitus (i.e. sugar diabetes). Despite the similar name, the two conditions are completely different. NDI does not involve disorders of blood glucose control.
Congenital NDI manifests at birth and is a life-long condition with a normal life expectancy. It is considered an orphan condition in the US and Europe: the best estimate is that for every 1 million males born in the US, four are likely to have X-linked congenital NDI.
Currently there is no effective therapy for NDI. Current management requires patients to drink as much fluid as they excrete to prevent dehydration. Patients are also prescribed a thiazide diuretic and must maintain a extremely low sodium diet (0.5 g/day). While often onerous, especially the ultra-low sodium diet, these measures are minimally effective. They may also be prescribed non-steroidal anti- inflammatory drugs or NSAIDs, but these can cause additional kidney damage with chronic use. In an attempt to maintain a semblance of a normal lifestyle, NDI patients can succumb to the temptation to void less frequently. This behavior can result in an enlarged bladder, which can cause an obstructive nephropathy and lead to kidney failure. There is a compelling clinical need for an effective therapy. A therapy that significantly reduces urine output would be a tremendous benefit to children suffering from NDI.