AC-200, an endogenous human protein produced by bone cells, was evaluated in a rodent model of chronic kidney disease (CKD) in which bone loss is rapid and substantial. The effects of AC-200 on bone and mineral metabolism were evaluated in partially nephrectomized rats (5/6 Nx). These rats have reduced renal function which leads to elevated levels of serum phosphate and parathyroid hormone (PTH).
Recombinant AC-200 or vehicle control were administered for 14 days by intravenous injections to 5/6 Nx rats. Serum and urine biochemistry assays were performed to determine the effects on renal function and mineral metabolism. Femurs were analyzed by X-ray and histology to determine effects on both cortical and trabecular bone.
According to the company, AC-200 administration resulted in marked reductions in serum phosphorus and PTH levels compared to those in vehicle treated controls. The vehicle treated 5/6Nx group showed the expected changes in bone architecture due to the loss of kidney function, such as thinner trabecular bone in the metaphysis, increased cortical bone resorption and increased fibrosis in the marrow space. In contrast, in rats administered AC-200, bone architecture resembled that of sham operated controls. These data suggest that AC-200 offers a dual benefit in CKD, potentially correcting not only mineral abnormalities but also reducing bone pathology associated with complications such as hip fracture in CKD patients, the company said.
Dawn McGuire, chief medical officer of Acologix, said: "Results of AC-200 administration in this standardized CKD rodent model provide strong support for clinical development of AC-200. AC-200 offers a unique opportunity to address both hyperphosphatemia and pathologic bone loss, major complications of CKD, with a single agent."