- Dysregulation of CYP24 linked to chronic kidney disease -
MARKHAM, ON, June 15 /PRNewswire/ - Cytochroma today announced the publication of new data from studies in a preclinical model indicating that chronic kidney disease (CKD) is associated with markedly increased expression of the vitamin D catabolic enzyme, CYP24, which contributes to vitamin D insufficiency and resistance to vitamin D therapy. Parallel analysis of kidney biopsies obtained from CKD patients confirmed abnormal CYP24 expression in human disease as well. The findings were published in Kidney International's advance online publication, and will appear in a forthcoming print edition of Kidney International.
"Our research raises the possibility that aberrantly elevated CYP24 accelerates progression of kidney disease," stated Dr. Martin Petkovich, Cytochroma's Chief Scientific Officer. "Adequate vitamin D hormone supply will normally suppress kidney inflammation and reduce the associated risk of irreversible fibrosis. CYP24, however, inactivates vitamin D hormone and deprives the kidneys of adequate supply. CYP24 also inactivates all currently available vitamin D therapies, making it difficult to treat the hormone deficit in the kidneys."
This newly published research examined CYP24 regulation in relation to vitamin D status in normal rats and in adenine-treated uremic rats, a preclinical model of CKD. As expected, when normal rats were fed a vitamin D deficient diet, CYP24 expression decreased in order to preserve existing vitamin D stores. In contrast, CYP24 expression increased in rats with renal impairment and remained elevated when these rats were fed a vitamin D deficient diet, demonstrating that kidney damage significantly altered the regulation of CYP24 expression. Increased CYP24 expression was separately confirmed in kidney biopsies obtained from CKD patients, suggesting that CYP24 is similarly dysregulated in human renal disease.
These findings indicate that new vitamin D products which resist catabolism by CYP24 and/or minimize CYP24 expression may offer significant advantages over currently available therapies for CKD patients.
About Chronic Kidney Disease
CKD is a condition characterized by a progressive decline in the function of the kidney, which is normally responsible for excreting waste and excess water from the body, and for regulating various hormones. CKD is classified in five different stages - mild (stage 1) to severe (stage 5) disease - as measured by the kidney's glomerular filtration rate. According to the National Kidney Foundation, CKD afflicts over 26 million people in the United States, including more than eight million patients with moderate (stages 3 and 4) and severe (stage 5) forms of CKD. In stage 5 CKD, kidney function is minimal to absent and patients require regular dialysis or a kidney transplant for survival.
About Vitamin D Insufficiency
Vitamin D insufficiency is a condition in which the body has low blood levels of vitamin D prohormones, collectively known as 25-hydroxyvitamin D. An estimated 70-90% of CKD patients have vitamin D insufficiency, which can lead to secondary hyperparathyroidism (SHPT) and resultant debilitating bone diseases. Mounting evidence continues to link vitamin D insufficiency with progression of CKD, cardiovascular morbidity, and increased mortality.
CYP24 is a cytochrome P450 24-hydroxylase also known as the "vitamin D catabolic enzyme" because it acts only on vitamin D and its metabolites, hormones and analogs. Intracellular expression of CYP24 regulates tissue response to vitamin D therapies. In healthy individuals, CYP24 has a protective role: its expression rapidly increases in proportion to intracellular levels of vitamin D hormone, thereby preventing potential toxicity. Abnormally elevated CYP24 in certain disease states, including CKD, is associated with vitamin D insufficiency and with resistance to vitamin D therapies.
Cytochroma is a clinical stage specialty pharmaceutical company focused on developing and commercializing proprietary products to treat and prevent the clinical consequences of vitamin D insufficiency and SHPT associated with CKD. The Company specializes in developing new vitamin D therapies which are designed to safely and effectively treat patients with stage 3, 4 or 5 CKD. Cytochroma has three product candidates in clinical development for CKD patients: CTA018 Injection and CTAP201 Injection are being developed for the treatment of SHPT in stage 5 CKD, while CTAP101 Capsules are being developed for the treatment of vitamin D insufficiency and associated SHPT in stage 3 and 4 CKD. Cytochroma also has a portfolio of compounds that inhibit CYP24 in early stage development.
For more information about Cytochroma, please visit www.cytochroma.com.