how understanding the vaginal microbiome can help discover new drugs

The relationship between the human microbiome – that is, all the bacteria living in or on the human body – and health has been the subject of medical research for many years. But one area, the vaginal microbiome, remains relatively neglected.

“There is a big lack of innovation [in women’s health]says Dr. Jacques Ravel, whose more than 15 years of vaginal microbiome research is at the heart of LUCA Biologics, an American biotechnology company developing live microbiome-based drugs for urogenital and reproductive health.

LUCA is the first biotech spun off from Seed Health, a venture-backed company developing microbial applications for medicine, consumer health and the environment.

“Generally, conditions such as bacterial vaginosis (BV) and urinary tract infection (UTI) have been dismissed by pharmaceutical companies as symptoms, or not worthy of drug targeting, because antibiotics are extremely cheap,” says the co-founder and co-CEO of Seed. Raja Dhir.

Studying the vaginal microbiota

In a healthy vagina, the microbiome is usually dominated by strains of the bacterial species Lactobacillus. When the microbial composition of the vagina is disrupted and other microorganisms become dominant – a process known as dysbiosis – infections and other urogenital disorders can occur.

LUCA’s mission is to develop treatments that help restore a healthy and balanced ecology to the vagina. To achieve this, one must first identify which bacterial compositions create the optimal environment for vaginal health, and it is precisely this that has been the focus of Ravel’s work.

For more than a decade, Ravel has collected nearly daily vaginal swabs from participants to paint a detailed picture of the relationship between the vaginal microbiome and certain health conditions. He likens his approach to studying footage of a traffic accident to figure out what caused it.

“If you can unwind that movie and start looking at what happened before the condition arose, then you can start to understand the contribution of each individual member. [of the microbiota] to the result,” he says.

The LUCA team used multiomics – the analysis of a range of omics data – to identify the genes of each strain present in the vaginal microbiomes of thousands of people. Characterizing the different microbial communities found in participants’ vaginas has allowed LUCA to define the healthy composition it aims to replicate through medicine.

“Through a very long period of interrogation, we were able to arrive at a handful of microbial genes and mechanisms that are distinctive of the stable and protective ecologies of the vaginal microbiome,” says Dhir.

If one is able to modulate or transplant an entire healthy ecology into the vaginal microbiome, he says, this can restore the microbial diversity of the vagina and foster an environment that protects the host against recurrence of infection. In 2019, a small study by researchers in Israel found that four out of five participants with relapsed and refractory BV experienced long-term remission after vaginal microbiome transplantation from healthy donors.

Respond to an unmet need

LUCA is not alone in developing treatments based on the science of the vaginal microbiome. California-based Osel’s live biotherapeutic product LACTIN-V, for example, is currently in clinical trials for recurrent UTIs, a condition that is usually resistant to antibiotics and can become fatal if left untreated. is not resolved.

LUCA’s first drug candidate, which will enter clinical trials this year, targets urinary tract infections. The company is also developing a treatment for BV, which has been linked to exhaustion Lactobacilli in the vaginal microbiota and is likely to recur. Ravel points out that effective BV therapy would also help protect against a host of other health complications; studies have shown that BV increases the risk of conditions such as pelvic inflammatory disease, sexually transmitted infections such as HIV, and even premature labor.

Osel has ongoing trials of LACTIN-V in BV, in vitro fertilization and premature birth – the latter also being targeted by LUCA with microbiome-based therapy. LACTIN-V is also tested in Lactobacillus– deficient women at high risk of contracting HIV.

The impact of the vaginal microbiome on preterm labor is less clear than other conditions that are usually the result of pathogens becoming dominant and causing infection. In 2019, research from Ravel’s lab identified specific types of bacteria associated with a higher risk of preterm labor, as well as a link between levels of the antimicrobial peptide β-defensin-2 in vaginal microbiota and risk. of premature delivery. .

“It’s not yet clear exactly what the triggers are, but we do know that vaginal dysbiosis is at least very strongly associated with [preterm birth],” he explains.

Ravel says it’s “ridiculous” that preterm birth rates remain relatively constant despite decades of research, but he hopes LUCA therapy will be the answer.

The future of vaginal health?

It’s still early days, though. Sarah Bundra, gender health analyst at GlobalData, said Pharmaceutical technology that while targeting the vaginal microbiome to treat gynecological conditions is becoming increasingly popular, the approach “needs stronger evidence” before it becomes a mainstream target in the pharmaceutical space.

According to Ravel, the key to unlocking effective drugs is to start with the end goal; Establishing a model of health first, he says, helps to better understand how to keep disease at bay for good.

“You can treat a disease, but without understanding the state to return to, you cannot cure it completely.”

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