• Fri. Jul 19th, 2024

Femtechs take on women’s health

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Jun 14, 2024 #Femtechs, #Health, #womens

The once-neglected areas of pregnancy loss and fertility are now hot new areas of research. Hoffmann has collaborated with Henriette Svarre Nielsen, a specialist in obstetrics and gynecology at Copenhagen University Hospital Hvidovre, to analyze DNA in the blood of hundreds of women who had miscarriages.

Their work has focused on cell-free fetal DNA circulating in the maternal bloodstream, which can reveal the health of the fetus while avoiding the need for invasive (and often inaccurate) biopsies, such as amniocentesis, which carry a risk of miscarriage.

Hoffmann and Nielsen used a structural quirk of fetal chromatin to distinguish it from maternal DNA. “You get different chromatin structures, and that means you get different fragment sizes for specific sequences,” says Hoffmann. The pair led the first large-scale validation of cell-free fetal DNA2 and found that this non-invasive blood test can detect aneuploidy (where the fetus has an incorrect number of chromosomes) to provide an explanation for pregnancy loss.

The underlying cause of these chromosomal abnormalities, however, remains largely unknown. Hoffmann was involved in a genome-wide association study of more than 100,000 women in the UK Biobank3, which identified mutations in the SYCE2 gene associated with an increased risk of pregnancy loss. SYCE2 is part of a multi-protein complex that controls genetic recombination during meiosis.

Hoffmann is forming a femtech startup to commercialize biomarkers and diagnostics for pregnancy loss. It is funded by the Bioinnovation Institute in Denmark, part of the Novo Nordisk Foundation. The startup will also focus on proteome analysis of plasma using AI to develop predictive models, which should lead to new diagnostics and therapeutics for pregnancy loss further down the line.

For some miscarriages, the cause is not necessarily fetal chromosomal alterations, but the mother’s vaginal microbiome. In 2019, a team led by Gregory Buck at Virginia Commonwealth University showed that preterm birth was associated with vaginal dysbiosis4, including the depletion of Lactobacillus species. Lactobacilli, as the name suggests, produce lactic acid, which brings the vaginal pH down to around 4.5 — a range that keeps infections at bay. Several research groups have found depletion of lactobacilli in the vaginal microbiomes of women who experience pregnancy loss, and some studies have associated this microbial imbalance with higher levels of proinflammatory cytokines5. These cytokines lead to inflammation, which could be responsible for the symptoms seen in some women with recurrent pregnancy loss, who often have vaginal discomfort and dysbiosis, including discharge during pregnancy. In the same year, the first small trial of vaginal microbiome transplantation took place6. A team of microbiologists and gynecologists in Israel treated five women with intractable bacterial vaginosis, four of whom saw remission.

If vaginal microbiome transplantation can treat dysbiosis, then the next logical step would be to treat pregnancy loss with a microbiome transplant. This is precisely what Nielsen aimed to do in 2021 in a proof-of-principle n-of-1 trial, in part funded by Copenhagen-based Freya Biosciences. The cervicovaginal secretions from a healthy donor were safely administered to a woman who had previously experienced recurrent pregnancy loss, resulting in a successful pregnancy. Although the precise bacterial composition of the microbiome transplant was not known, the mother’s vaginal microbiome shifted from a dominance of Gardnerella bacterial species to a mix of Lactobacillus species (dominated by L. crispatus and L. jensenii). Freya secured $38 million in series A funding in December 2023 for further clinical trials using the FB101 microbiota product in women who are undergoing assisted reproduction, with funding led by Sofinnova Partners and OMX Ventures.

Including pregnant women in clinical trials7 is a regulatory hurdle most companies have struggled to overcome. The thalidomide scandal, where more than 10,000 children were born with severe deformities after their mothers took the drug during pregnancy, led to tight restrictions on clinical trials from the US Food and Drug Administration (FDA) and global regulators. Some consider such restrictions responsible for slowing the flow of capital into the area: “If the regulatory risk is too high, the investors aren’t willing to put money in,” Obremskey says.

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