ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: FR-PO486

INS-3001 Efficiently Inhibits Severe Vascular Calcifications by Direct Interference with Vessel Wall Calcification

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Verhulst, Anja, University of Antwerp, Antwerp, Antwerp, Belgium
  • Ivarsson, Mattias E., Inositec Inc., Zurich, Switzerland
  • Maj, Roberto, Inositec AG, Zurich, Switzerland
  • Neven, Ellen, University of Antwerp, Wilryk, antwerp, Belgium
  • D'Haese, Patrick C., University Antwerp, Edegem, Belgium
Background

Prevention/treatment of vascular calcification currently is based on controlling its most important risk factors. A new therapeutic approach with potential higher efficacy consists in the administration of molecules directly interfering with the calcification process in the vessel wall, such as INS-3001. This abstract reports about the administration of INS-3001 in a rat model of vitamin D-warfarin induced vascular calcifications (pooled data of 3 independent studies).

Methods

Calcification was induced in male rats (8 weeks) by warfarin (3mg/g diet) administration during 6 days and by 4 consecutive daily administrations of vitD3 (100.000 IU/kg) starting on day 1 of the warfarin administration. Rats were randomly assigned to different groups: vehicle, and INS-3001 groups of 12, 25, 2x25, 50 and 2x50 mg/kg/day. Treatment was administrated sc. for 7 days (starting together with vitD). Animals were sacrificed on the 8th day. Vascular calcification was evaluated on Von Kossa stained tissue sections of the thoracic/abdominal aorta and by measurement of the total Ca content of the thoracic/abdominal aorta and the carotid/femoral arteries by atomic absorption spectrometry.

Results

Mortality rate was 38% (15/40) in the vehicle group, similar -33% (4/12) and 44% (5/12)- in the 1x25 and 1x12.5 mg/kg/day dose groups, numerically lower -15% (3/19), 21% (4/19)- in the 2x50, 1x50 mg/kg/day dose groups and significantly lower 0% (0/18) in the 2x25 mg/kg/day dose group. In the abdominal aorta, significantly lower Von Kossa positivity (area%) was measured in the INS-3001 groups compared to the vehicle group (3±5%, 6±4%, 8±7%, 15±3%, 20±3% and 28±10% in respectively the 2x50, 50, 2x25, 25, 12.5 mg/kg/day and the vehicle group). Total Ca content of the abdominal aorta was also significantly lower in the INS-3001 (not the 12.5 and 25 mg/kg/day) groups compared to the vehicle group (2.8±3.7, 6.1±5.0, 7.4±6.9, 14.9±7.0, 15.6±9.4 and 14.9±7.5 mg/g tissue in respectively the 2x50, 50, 2x25, 25, 12.5 mg/kg/day and the vehicle group. Similar reductions in area% Von Kossa positivity and total Ca content were seen in the thoracic part of the aorta, and the arteria femoralis and carotis.

Conclusion

In conclusion, INS-3001 is a promising molecule for the treatment of CKD and non-CKD induced vascular calcifications.

Funding

  • Commercial Support – Inositec AG, Switzerland