# Therapy for ectopic calcification in pseudoxanthoma elasticum

> **NIH NIH R43** · LARIX BIOSCIENCE, LLC · 2023 · $285,766

## Abstract

Therapy for ectopic calcification in pseudoxanthoma elasticum
Abstract
 Pseudoxanthoma elasticum (PXE) is a rare monogenic disease that leads to ectopic calcification of the eyes,
skin, and vasculature. PXE results from loss-of-function mutations in the ABCC6 gene. Normally, ABCC6
transports ATP from the liver into circulation where it is then converted into adenosine monophosphate (AMP)
and inorganic pyrophosphate (PPi) by the enzyme Ectonucleotide pyrophosphatase/phosphodiesterase-1
(ENPP1). PPi in circulation is a potent inhibitor of ectopic calcification; it antagonizes the ability of inorganic
phosphate to crystallize with calcium to form hydroxyapatite. Patients with PXE have a 70% reduction of normal
circulating levels of PPi which results in late-onset generalized systemic calcification. PPi replacement therapy
has been challenging given the short half-life and misconceived notion that it could not be delivered orally.
Recently, we have developed a proprietary gastric-release salt form of PPi for oral administration that achieves
clinically meaningful increases in circulating PPi in mice and in humans. Orally delivered PPi in ABCC6-/- mice
attenuates calcification and establishes proof-of-concept. In this Phase 1 project, we will conduct
pharmacokinetic and toxicology studies and then evaluate Lys-PPi in an animal model of PXE. Phase 2 work
will comprise IND-enabling studies, culminating in the filing of an IND. A successful outcome of this work will
provide a proprietary mechanism-based first-in-class therapy for PXE and other disorders of abnormal ectopic
calcification.

## Key facts

- **NIH application ID:** 10763057
- **Project number:** 1R43AR083332-01
- **Recipient organization:** LARIX BIOSCIENCE, LLC
- **Principal Investigator:** JAMES W LARRICK
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $285,766
- **Award type:** 1
- **Project period:** 2023-09-21 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763057

## Citation

> US National Institutes of Health, RePORTER application 10763057, Therapy for ectopic calcification in pseudoxanthoma elasticum (1R43AR083332-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10763057. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*