# A long acting parathyroid hormone (PTH) 1-34 for treatment of hypoparathyroidism

> **NIH NIH R43** · PROLYNX, LLC · 2020 · $245,871

## Abstract

A long acting parathyroid hormone PTH(1-34) for treatment of hypoparathyroidism
Project Summary
Hypoparathyroidism is a rare endocrine disorder characterized by low calcium (Ca2+) and high
phosphate (Pi) levels in the setting of absent or low parathyroid hormone (PTH). Overall, an
estimated 60,000 to 115,000 individuals in the United States have chronic hypoparathyroidism;
most cases (~75%) result from neck surgery, and the remaining are non-surgical or, rarely,
genetic disorders. Most hypoparathyroid patients require lifelong high-dose Ca2+ and vitamin D
supplements. The associated side effects and the difficulty of maintaining stable serum and urine
Ca2+ levels with these regimens makes PTH replacement therapy a desirable or necessary option
for many.
Two PTH replacement drugs are commonly in use, Natpara, the recombinant form of natural PTH,
and teriparatide (Forteo), the 34-amino acid N-terminus polypeptide of the natural hormone. Both
these drugs have short half-lives after subcutaneous administration, requiring once-daily injection.
Neither adequately mimics the physiological levels of PTH secretion. Indeed, 5 of the 13 members
of the FDA Advisory Committee voted against approval of Natpara for hypoparathyroidism, stating
that “dose could be better optimized to closer mimic physiological levels, resulting in more salutary
effects”.
We have developed a chemically controlled, ultra-long acting delivery system to support once-
weekly to once-monthly administration of peptides and other small molecules. With this system a
therapeutic agent is covalently attached to a hydrogel microsphere depot by a cleavable β-
eliminative linker. Upon subcutaneous injection the linker slowly cleaves and releases the drug.
The current proposal seeks to demonstrate the feasibility of utilizing this system for delivery of
PTH.
Specifically, we will prepare and characterize two hydrogel microsphere conjugates of PTH(1-34),
one suitable for once-weekly and the second suitable for once-monthly administration. Since
PTH(1-34) itself is not sufficiently stable for a once-monthly dosing regime, the latter conjugate
will be prepared using a more stable PTH(1-34) analog with similar physiological activity. We will
perform pharmacokinetic and pharmacodynamic studies of the compounds in thyroid-
parathyroidectomized rats to evaluate the potential of one or both these compounds as an
improved therapeutic agent for hypoparathyroidism.

## Key facts

- **NIH application ID:** 10008534
- **Project number:** 1R43DK125144-01
- **Recipient organization:** PROLYNX, LLC
- **Principal Investigator:** Eric L Schneider
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,871
- **Award type:** 1
- **Project period:** 2020-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10008534

## Citation

> US National Institutes of Health, RePORTER application 10008534, A long acting parathyroid hormone (PTH) 1-34 for treatment of hypoparathyroidism (1R43DK125144-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10008534. Licensed CC0.

---

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