Periodic Reporting for period 1 - BLASTOID-DISCOVERY (Human blastoids: a drug discovery platform for women’s reproductive health)
Reporting period: 2023-11-01 to 2025-04-30
The first weeks of human pregnancy are of crucial importance, as early abnormalities or insults result in infertility. Therapeutics acting at the onset of embryonic development would offer tremendous opportunities to improve public health through effective family planning and to reduce an ongoing global fertility decline with profound economic, social, environmental, and geopolitical consequences. Unfortunately, a drug development program on human embryos is unfeasible due to the inaccessibility and scarcity of embryos, and the associated ethical issues. As a result, the failure rate for reproductive health drugs is high for all major In Vitro Fertilization (IVF) and pharmaceutical companies.
Recently, an alternative approach arose from stem cells self-organizing into structures closely resembling pre-implantation embryos (blastocysts), which we have termed blastoids. Since stem cells can be proliferated on a large scale, this embryo model represents a scalable and ethically acceptable alternative amenable to drug screening and thus opens up numerous possibilities for therapeutic breakthroughs. Here, we have used human blastoids to discover molecules enhancing blastocyst development and implantation. These molecules will initially be used to supplement the IVF medium to promote the formation of highly potent blastocysts and improve IVF procedures.
Blastoids offer a unique opportunity to establish an early pregnancy drug discovery programme and provide an alternative to the use of animal and human embryos. This pathway has the potential to reduce the cost of drug development and increase the number of approved drugs for reproductive medicine. This project - BLASTOID-DISCOVERY - has developed a screening platform to discover molecules that support early pregnancy in humans and has founded a start-up company - dawn-bio - that has used this platform to discover seven molecules, to date that have been validated in a preclinical approach and improve the development of human blastocysts in vitro. These molecules may become therapeutics for reproductive health.
Recently, an alternative approach arose from stem cells self-organizing into structures closely resembling pre-implantation embryos (blastocysts), which we have termed blastoids. Since stem cells can be proliferated on a large scale, this embryo model represents a scalable and ethically acceptable alternative amenable to drug screening and thus opens up numerous possibilities for therapeutic breakthroughs. Here, we have used human blastoids to discover molecules enhancing blastocyst development and implantation. These molecules will initially be used to supplement the IVF medium to promote the formation of highly potent blastocysts and improve IVF procedures.
Blastoids offer a unique opportunity to establish an early pregnancy drug discovery programme and provide an alternative to the use of animal and human embryos. This pathway has the potential to reduce the cost of drug development and increase the number of approved drugs for reproductive medicine. This project - BLASTOID-DISCOVERY - has developed a screening platform to discover molecules that support early pregnancy in humans and has founded a start-up company - dawn-bio - that has used this platform to discover seven molecules, to date that have been validated in a preclinical approach and improve the development of human blastocysts in vitro. These molecules may become therapeutics for reproductive health.
- Development of a platform for molecular screening on human blastoids.
- Validation of the platform using known regulators of blastocyst development
- Validation of the platform using known regulators of blastocyst development
- Establishment of a start up - dawn-bio, a pre-clinical stage company was created by Alok Javali (CSO, former postdoc in the Rivron lab supported by this ERC-PoC grant), Peter Greiner (CEO, former Senior Vice President of Merck Fertility Franchise) and Nicolas Rivron (PI on this grant). The company (9 employees) is finishing a pre-clinical trial that enabled the discovery of 7 pre-clinically-validated molecules to improve In vitro fertilization procedures.
- Along with scientific societies, including the International Society for Stem Cell Research (ISSCR) and the European Society for Human Reproduction and Embryolgy (ESHRE), we have established an ethical framework for the research on Stem Cell-Base Embryo Models, including blastoids. This framework has been implemented, or is in the process of being implemented, in multiple countries of the EU, including France (implemented), Sweden (proposition to be validated) and the Netherlands (proposition to be validated).
- Along with scientific societies, including the International Society for Stem Cell Research (ISSCR) and the European Society for Human Reproduction and Embryolgy (ESHRE), we have established an ethical framework for the research on Stem Cell-Base Embryo Models, including blastoids. This framework has been implemented, or is in the process of being implemented, in multiple countries of the EU, including France (implemented), Sweden (proposition to be validated) and the Netherlands (proposition to be validated).