Targeting ZIP12-mediated Zn(2+) signaling as a treatment for pulmonary hypertension.

Targeting ZIP12 with the monoclonal antibody APL-9796 reduces pulmonary hypertension symptoms in rodent models and shows promise as a therapy for PAH.

• Why it matters: Pulmonary arterial hypertension involves abnormal remodeling of pulmonary arterioles, and ZIP12 is up-regulated in affected tissues, suggesting it may play a key role in disease progression. Addressing this gap could lead to novel treatments that directly target underlying molecular mechanisms.
• What they did: Researchers developed a humanized anti-ZIP12 monoclonal antibody, APL-9796, and tested its effects on cell proliferation, cytoskeletal remodeling, and contractility in human PASMCs and fibroblasts, as well as in rodent models, including dose-dependent efficacy studies in humanized rats.
• The result: APL-9796 normalized intracellular Zn 2+ levels, suppressed cell proliferation, improved cardiopulmonary parameters, and was well tolerated in phase 1 trials, indicating ZIP12 targeting may offer a promising therapeutic approach for PAH.