FSH-blocking therapeutic for osteoporosis
Sakshi Gera1, Tan-Chun Kuo1, Anisa Azatovna Gumerova1
1Center for Translational Medicine and Pharmacology and The Mount Sinai Bone Program, Departments of Medicine and of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, United States.
Elife
|September 20, 2022
Summary
A novel antibody, MS-Hu6, effectively blocks follicle-stimulating hormone (FSH) action, showing promise for treating osteoporosis and other diseases. This durable and manufacturable antibody is ready for human testing.
Area of Science:
- Endocrinology and Immunology
- Pharmacology and Drug Development
Background:
- Follicle-stimulating hormone (FSH) is an actionable target for osteoporosis, obesity, and Alzheimer's disease.
- Blocking FSH action has demonstrated therapeutic potential in preclinical models.
Purpose of the Study:
- To evaluate the efficacy and safety of MS-Hu6, a first-in-class humanized FSH-blocking antibody.
- To assess MS-Hu6's potential for preventing and treating osteoporosis.
Main Methods:
- Utilized a Good Laboratory Practice (GLP)-compliant platform for efficacy and safety studies.
- Conducted biodistribution studies with 89Zr-labeled MS-Hu6 in mice and monkeys.
- Optimized formulation using protein thermal shift assay and assessed immunogenicity via ELISpot assays.
Main Results:
- MS-Hu6 demonstrated efficacy in preventing and treating osteoporosis in mice.
- Biodistribution studies showed localization to bone and bone marrow with a long half-life (7.5 days) in humanized mice.
- The antibody formulation was stable, and MS-Hu6 showed no significant immunogenicity in preclinical assays.
Conclusions:
- MS-Hu6 is an efficacious, durable, and manufacturable FSH-blocking antibody.
- The preclinical data support the advancement of MS-Hu6 for human clinical trials.
- MS-Hu6 represents a promising therapeutic candidate for FSH-targeted diseases.
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