Progressnotes - October/November 2012
- About MUSC Health
The world owes penicillin to scientific serendipity: Alexander Fleming discovered penicillin when he noticed that the mold growing on a discarded Petri dish was destroying the bacteria.
Could a similar moment of scientific serendipity bring the world a much-needed drug to treat kidney disease in diabetic patients?
Rick G. Schnellmann, PhD, Chair of the Department of Drug Discovery and Biomedical Sciences at MUSC, and his collaborators, Leah Siskind, PhD, made a startling discovery while using suramin, a decades-old drug historically used for treating sleeping sickness.
When Schnellmann and his colleagues observed that suramin, routinely used in the laboratory to block growth factor receptor binding, was not blocking the receptor in their studies, they believed that their experiment had failed. Instead, as they soon discovered, suramin had stimulated the proliferation of renal epithelial cells.
Unlike Fleming’s discovery, established a decade after the initial observation, Schnellmann quickly realized the significance of his team’s findings: suramin’s ability to stimulate renal cell repair and regeneration could hold therapeutic potential for kidney diseases.
Certainly, better pharmacological options for chronic kidney disease (CKD) are desperately needed. In the opinion of John Arthur, M.D., Professor in MUSC’s Division of Nephrology, “There are currently no good drugs for treating CKD. Renin angiotensin system blockers can slow progression of kidney disease but are of limited benefit once diabetic nephropathy is well established.”
Many patients with diabetes develop CKD that progresses to end-stage renal disease (ESRD), necessitating dialysis. Diabetic nephropathy, which develops as the kidneys are chronically exposed to hyperglycemia and progresses to inflammation and fibrosis and eventually kidney failure, is implicated in 50% of ESRD cases. The costs of treating ESRD are staggering: in 2010, the last year for which data are available, Medicare paid out $32.9 billion, more than the entire budget of the National Institutes of Health.
Schnellman and his collaborators have shown that suramin blocks initiating events in diabetes-induced kidney injury in rodent models of early-stage diabetes1 and reverses damage and restores kidney function in models of late-stage diabetes2 by reducing the levels of proinflammatory and profibrotic factors in the kidney.
In contrast to diabetes-induced kidney damage, which develops over time, acute kidney injury (AKI) can lead to loss of kidney function in only a few days, sometimes due to trauma or exposure to a nephrotoxic drug. Suramin was effective in reversing AKI in rodent models even when given 24 hours after maximal renal damage.3,4
Schnellmann and Arthur have begun a collaboration to design and implement a phase 1 trial of suramin for the treatment of AKI, and they anticipate beginning suramin in patients with CKD soon. The dosing requirements and safety profile of suramin are well known as it is already an approved treatment for sleeping sickness and river blindness in humans. Because suramin, which is injected, has a long half-life, treatment regimens for patients would not be overly burdensome.
In the words of American writer Lawrence Block, serendipity is “look[ing] for something, find[ing] something else, and realiz[ing] that what you’ve found is more suited to your needs than what you thought you were looking for.” Schnellmann’s laboratory did just that, and what they found could improve the health and quality of life for patients with AKI or CKD and substantially lessen the enormous economic burden associated with ESRD.
¹ Korrapati MC, et al. Diabetes-induced renal injury in rats is attenuated by suramin. JPET 2012:343 (1):34-43.
² Korrapati MC, et al. Suramin: a potential therapy for diabetic nephropathy. PLoS One. Submitted, 2013.
³ Korrapati MC, et al. Recovery from glycerol-induced acute kidney injury accelerated by suramin. JPET 2012; 341(1): 126-136.
⁴ Zhuang S, et al. Suramin promotes recovery from renal ischemia/reperfusion injury in mice. Kidney Int. 2009;75(3):304-311.
This article originally appeared in the August 2013 issue of Progressnotes.