Continuous calcium sensor patch for hypoparathyroid patients

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PROJECT SUMMARY Hypoparathyroidism (hypoPT) is a disease characterized by absence of circulating parathyroid hormone (PTH), the major hormonal regulator of extracellular calcium homeostasis. Symptoms of hypocalcemia range from tingling and muscle cramps and neuropsychiatric symptoms to seizures and life-threatening laryngospasm. Treatment with calcium and vitamin D partially relieves symptoms of hypocalcemia, but can also “over-shoot,” leading to episodes of hypercalcemia, which, in the absence of the renal calcium-conserving effect of PTH, lead to renal parenchymal calcification and long-term irreversible renal damage. Indeed, chronic kidney disease is found in 41% of hypoPT patients and is directly associated with the proportion of time with hypercalcemia. As such, even with today’s best practices, the daily levels of calcium fluctuate down and up, resulting in hypocalcemia and hypercalcemia, with serious and irreversible organ damage and mortality. HypoPT patients would benefit greatly from knowing their calcemic variability in real time, giving them a chance to adjust their treatment individually and dynamically. We propose to develop a sensor patch technology featuring biocompatible “hydrogel microfilaments” that can penetrate the skin while allowing for in situ optical fluorescence sensing of analytes in dermal interstitial fluid. The non-hollow structure of the microfilaments allows for easy fabrication, the porous nature of hydrogels ensures that calcium in interstitial fluid can diffuse into the filaments, the large internal surface of hydrogel allows for analytes to interact with a large number of conjugated fluorescent aptamers for signal generation, and optical transparency allows for in situ optical sensing with a wearable fluorometer with no fluid extraction needed. Our central hypothesis is that a skin patch with hydrogel microfilaments can enable repeated in vivo calcium sensing. Upon completion of these aims, the expected outcome is a full characterization of the performance and limits of a microfilament-based continuous sensor of calcium, and demonstrations of in vivo sensing in a live rat model and in the interstitial fluid of human subjects. These results are expected to have an important positive impact because they will provide a strong proof of principle for clinical testing of a continuous calcium sensor, ultimately providing new opportunities for individualized treatment of patients with hypoPT to maintain calcium homeostasis and reduce irreversible kidney damage and deadly laryngospasm. More broadly, this project will propel this minimally invasive sensing technology a step forward towards the rapidly approaching new paradigm of precision monitoring and medicine.