Autoimmune Hypoparathyroidism Drug Development

Autoimmune hypoparathyroidism is the most common cause of nonsurgical hypoparathyroidism. This condition can occur as an isolated feature or as a part of the autoimmune polyglandular syndrome type I (APS-I). Treatment and management of hypoparathyroidism mainly rely on the patients' absorption of calcium. The future treatment study of hypoparathyroidism may focus on antibody or cell-based therapeutic strategy development. As an industry-leading biopharmaceutical company, Creative Biolabs has an advanced platform with the latest technologies and professional experts. We are capable of providing global customers with reliable drug development services.

Introduction to Autoimmune Hypoparathyroidism

Autoimmune hypoparathyroidism may manifest as an isolated disorder or, more frequently, in combination with other autoimmune conditions. Autoimmune hypoparathyroidism occurs in autoimmune polyendocrinopathy syndromes (APSs) such as APS type 3 when associated with autoimmune thyroid diseases, or APS4 when occurring in combination with other non-thyroid autoimmune diseases. Autoantibodies against parathyroid autoantigens (NALP5Abs and CaSRAbs) have been described as associated with autoimmune hypoparathyroidism, but their specificity and sensitivity for the diagnosis of autoimmune hypoparathyroidism are low. In addition, it is not clear whether they can be simply considered as an epiphenomenon or marker of the disease or whether they have a real pathogenetic role. For this reason, they are not assessed routinely in clinical practice. On the other hand, the assessment of other organ-specific autoantibodies in the presence of established idiopathic hypoparathyroidism should be advised to indirectly suggest possible autoimmune pathogenesis of the disorder.

Fig.1 Parathyroid hormone (PTH) deficiency results in low blood Ca²⁺ increased blood PO₄^3-, and decreased renal Ca²⁺ reabsorption. (Gafni, 2019)

Treatment of Hypoparathyroidism

In contrast to most hormone deficiencies, for which hormone replacement is the mainstay of therapy, hypoparathyroidism has been conventionally treated with high-dose vitamin D (cholecalciferol or ergocalciferol) and calcium supplements or with activated vitamin D and calcium supplements. Calcium carbonate, which is 40% by weight elemental calcium, is given orally, is economical, and is widely available. Because an acidic environment is required for effective absorption of calcium carbonate, alternatives that do not require a low gastric pH, such as calcium citrate, are recommended for persons taking acid-blocking therapy. Patients who are taking levothyroxine, which is poorly absorbed when taken with calcium, should be instructed to always take the medications separately or to consistently take them together.

Potential of Antibody-Based Therapeutic Strategies

Antibodies to the calcium-sensing receptor (CaSR) that activate signaling can suppress PTH secretion leading to hyperparathyroidism. Antibodies against the extracellular domain of the CaSR are present in a subset of patients with isolated hypoparathyroidism. In one study, 14 of 25 patients with autoimmune hypoparathyroidism had circulating antibodies that were reactive to the extracellular domain of the CaSR. Antibodies to the parathyroid cell surface were present in 8 of 23 cases of idiopathic hypoparathyroidism. Other studies have shown varying rates of anti-CaSR antibody positivity. These researches imply the antibody-based therapeutic strategies may be effective in hypoparathyroidism.

Custom Services of Autoimmune Hypoparathyroidism Drug Development

Focusing on the drug development of autoimmune disease for years, Creative Biolabs has accumulated enormous experience and resources. Hundreds of customer-satisfied precedents have shown how professional and reliable our services are. With advanced technologies, high-degree experts, and experienced technicians, we are capable of providing high-quality services including but not limited to:

• Monoclonal Antibody Development for Hypoparathyroidism
• Bispecific Antibody Development for Hypoparathyroidism
• Cell-based Therapy for Hypoparathyroidism

The novel therapeutic strategies of hypoparathyroidism still need to explore. With multiple advantages such as technologies, specialists, experience, and experiment conditions, Creative Biolabs aspires to help global researchers to promote the drug development of hypoparathyroidism through our reliable services. If you are interested in cell-based therapy or antibody development services, please feel free to contact us for more information.

Reference

1. Gafni, R. I.; Collins, M. T. Hypoparathyroidism. N Engl J Med. 2019, 380(18): 1738-1747.

For Research Use Only | Not For Clinical Use