helping girls with premature ovarian insufficiency
This innovative device is funded by the Frankel Innovation Initiative, a $20 million fund made possible by a generous donation from the Maxine and Stuart Frankel Foundation that supports the research and development of life-saving therapies at Michigan Medicine.
Female childhood cancer survivors are a growing patient population who suffers from premature ovarian insufficiency (POI), a common and significant complication of anticancer therapy that damages the ovaries. The toxicities associated with anticancer treatments adversely affect ovarian function and hormone production before puberty, leading to delayed physical and psychosocial development in young girls and chronic health issues later in life.
Currently, the standard of care is hormone replacement therapy (HRT), which is not designed for adolescent girls and is inadequate for physiological puberty induction.
University of Michigan’s Ariella Shikanov, Ph.D., and Molly Moravek, M.D., M.P.H., M.S.C.I., have developed ArtOva, a novel polymer capsule that contains functioning ovarian tissue from a healthy donor and can be transplanted into adolescent girls with POI. This ovarian graft will restore the patient’s ovarian endocrine function and restore physiological balance while avoiding the side effects of HRT, immunosuppression, and the risks of cancer recurrence following ovarian auto-transplantation.
“We want to offer adolescent girls an alternative to hormone replacement therapy, which was designed to manage postmenopausal symptoms and does not address the needs of POI patients,” comments Dr. Moravek. “Our technology was designed specifically for these pediatric POI patients.”
The immune-isolation capsule can be easily placed just under a patient’s skin and replaced annually. It is designed to accommodate structural and functional changes in the encapsulated ovarian tissue during the menstrual cycle, support follicle growth and expansion, and allow for the exchange of hormones. ArtOva prevents the patient’s immune cells from infiltrating the implant, which minimizes the chance of tissue rejection while still allowing the diffusion of nutrients and oxygen.
“We are readying the program for Phase I clinical trials,” says Dr. Shikanov. “Although this is a lifelong treatment, our research indicates that insurance companies have a willingness to pay given the high cost of POI-related side effects and health complications.”
Hormone replacement therapy, the current and only treatment for POI, was designed to treat postmenopausal symptoms, is inadequate for physiological puberty induction, and results in long-term morbidity and an inferior quality of life. It only delivers two of the approximately dozen hormones normally secreted from the ovary and negatively affects the rate of bone development and metabolism, as well as increases the risk of diabetes, obesity, breast cancer, and potentially life-threatening thrombotic events over the long term.
The design of the immno-isolating device is tuned to the unique physiology of ovarian tissue. It uses an optimized dual-layer biomaterial capsule with donor ovarian tissue, which secretes hormones and bidirectionally interacts with endocrine organs and controls muscular-skeletal development at physiological rates. The capsule protects the graft from the innate and adaptive immune response while promoting the ovarian endocrine function. It has a degradable core to support follicle growth and expansion, as well as a nondegradable shell that allows the exchange of soluble factors, yet prevents infiltration of the immune cells from the host.
This innovative device will offer a minimally invasive method of transplanting donor ovarian tissue that would deliver all the hormones present in the ovary and help restore physiological balance, eliminating the challenges and risks associated with HRT. The capsule accommodates structural and functional changes in ovarian tissue associated with development, providing a crucial advantage over rigid encapsulation systems. In addition, a multitude of long-term morbidities stemming from POI will be prevented.
- Intellectual Property: Patent has been issued; pre-investigational new drug application has been filed
- Commercialization Strategy: Submit investigational new drug application; obtain investment funding; launch startupp
- Regulatory Pathway: Regulated by the FDA Center for Biologics Evaluation and Research; follow the IND approval pathway to be granted a Biologics License Application for commercialization
- Engage Investors: Engage venture capitalists and strategic investors who have a focus on regenerative medicine
- Product Launch Strategy: Advancing pre-clinical program to first-in-human clinical trials
- Conduct independent, IND-enabling biocompatibility, histology, and toxicology testing
- Develop a detailed clinical study protocol and budget for a Phase I clinical trial at the University of Michigan
- Establish investigator manual of operating procedures, data safety and monitoring plan, and statistical analysis plan to support IRB approval of Phase I clinical trial
- Assemble the documentation needed for the investigational new drug submission to the FDA