Abstract: SA-PO348
SNF472, a New Therapeutic Approach to Improve Outcomes in CKD Patients with Peripheral Artery Disease
Session Information
- Hypertension and CVD: Mechanisms
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Bassissi, Firas, Sanifit Therapeutics, Palma, Spain
- Ferrer, Miquel D., Sanifit Therapeutics, Palma, Spain
- Perez, Maria del mar, Sanifit Therapeutics, Palma, Spain
- Perelló, Joan, Sanifit Therapeutics, Palma, Spain
- Salcedo, Carolina, Sanifit Therapeutics, Palma, Spain
Background
Peripheral Artery disease (PAD) is a common vascular disease associated with functional impairment and increased risk of cardiovascular events in Chronic Kidney Disease (CKD) patients undergoing dialysis. Poor limb salvage outcomes and high post-amputation mortality in hemodialysis (HD) patients highlight the need for earlier medical therapies. Cilostazol (SOC) use stays limited and requires caution in this population. Clinical studies demonstrate associations between arterial calcification and adverse outcomes in PAD patients. SNF472, a selective calcification inhibitor that interferes in the formation and growth of hydroxyapatite, is under development for calciphylaxis. We evaluated the effects of SNF472 on limb functional recovery and blood perfusion in a rat model with Vitamin D3 (VitD)-induced arterial calcification.
Methods
Arterial calcification was induced in 32 SD rats using (VitD) by 3 consecutives daily s.c. dosing of 120 kIU/kg. Rats were divided into four groups and treated during 12 days by: vehicle s.c, vehicle p.o, SNF472 (20mg/kg/day, s.c.) or cilostazol (20mg/kg/day, p.o.). An additional group of 8 rats without VitD received vehicle only (sham). Efficacy was evaluated at day 12 and 5 days after treatment stop. Posterior limb blood perfusion was measured using Laser Doppler Imaging and limbs walking ability were evaluated by measuring Maximum Walking Distance (MWD) and Maximum Walking Time (MWT) using a treadmill. Rats were sacrificed 10 days after treatment stop, and aorta was collected for calcium analysis.
Results
VitD-induced arterial calcification was associated with decreased blood perfusion and impairment of limb walking ability (MWT and MWD) compared to sham. SNF472 reduced aorta calcification by 41% compared to vehicle. No effects of cilostazol on vascular calcification were observed. The inhibition of calcification in SNF472 treated animals was associated with significant higher limb blood perfusion compared to vehicle or Cilostazol (1.28 and 1.37-fold higher, respectively at D12: p< 0.001) and translated into significant improvement in limbs walking ability compared to vehicle (515±114 meters vs 334±187 meters, respectively: p<0.05).
Conclusion
Our results evidence that SNF472 may present a promising new therapeutic approach to treat PAD associated with high vascular calcification such as in CKD and HD patients
Funding
- Commercial Support –