Tucson Tech: Startup developing supplement to ease menopausal hot flashes

Since earning her Ph.D. from the University of Arizona in 1984, Roberta Diaz Brinton has devoted her career to unlocking the effect of female hormones on the brain and diseases like Alzheimer’s.

Now, she’s driving a UA technology startup developing a plant-based nutritional supplement to ease the hot flashes experienced by menopausal women — while continuing research on a drug therapy that can help regenerate brain cells to treat Alzheimer’s.

Brinton is director of the UA Health Sciences’ Center for Innovation in Brain Science, which in 2019 was awarded a $37.5 million grant from the National Institute of Aging to study a drug used to treat postpartum depression as a treatment for Alzheimer’s, a so far incurable neurodegenerative disorder that disproportionately affects women.

And with the help of a $2.5 million research grant from the National Institutes of Health’s National Institute on Aging, Brinton’s Tucson startup, NeuTherapeutics, recently launched an advanced clinical trial of its hot-flash supplement.

The company says its supplement, called PhytoSERM, promises menopausal women safe, effective relief of hot flashes without the increased risk of breast cancer that has been found to come with traditional hormone therapy.

“We developed PhytoSERM as a safe, natural and effective approach for menopausal symptoms to address an unmet need in women’s health,” Brinton said, noting that many women simply endure the symptoms due to their fear of breast cancer.

The grant will fund a Phase 2 clinical trial by NeuTherapeutics to evaluate the impact of its new dietary supplement, PhytoSERM, on more than 100 participants in the HF Relief Clinical Trial at the UA’s Clinical and Translational Sciences Research Center.

Safer treatment

PhytoSERM contains three phytoestrogens — naturally occurring compounds derived from plants that can function like estrogen, the primary female sex hormone, said Brinton, a UA Regents professor in pharmacology.

SERM stands for “selective estrogen receptor modulators,” hormone therapies that manage how estrogen works in the body.

The latest trial follows a double-blind, placebo-controlled Phase 1b/2a clinical trial in 2018 that enrolled 72 women and found that PhytoSERM was safe and well-tolerated while decreasing the number of hot flashes in women experiencing large numbers of hot flashes.

Hormone-replacement therapy with estrogen or progesterone, or both, in is a common treatment for menopausal hot flashes, which are the result of the body trying to cool itself in response to signals from the brain.

But hormone replacement has been linked to increased risk of breast cancer in multiple studies, prompting many women to avoid the therapy, said Brinton, who studied the area for three decades as a research professor at the University of Southern California before returning to the UA in 2016.

“There is that concern, and a large proportion of women elect not to receive hormone therapy because of fear of breast cancer, and so it became quite clear that in order to promote brain health through the estrogen pathways, I would also have to take on the challenge of sustaining breast health,” she said.

Because of the estrogen receptor in the brain they target, the plant-based phytoestrogens in NeuTherapeutics’ PhytoSERM don’t increase breast cancer risk, and may in fact reduce it, Brinton said, citing studies already conducted by breast cancer researchers.

PhytoSERM also has been shown in preclinical studies to boost overall brain function, though the recently launched study focuses on the treatment of hot flashes.

Soy and menopause

Soy isoflavones, plant-based compounds that mimic estrogen, have been used in over-the-counter nutritional supplements to treat menopausal symptoms for years, but their efficacy is variable.

Among thousands of molecules studied, Brinton’s research isolated three soy compounds that are most active with the targeted brain estrogen receptor to create PhytoSERM.

Because PhytoSERM is a dietary supplement, the company doesn’t need to conduct clinical trials and win approval from the U.S. Food and Drug Administration, like a new drug.

The FDA simply requires makers of dietary supplements to have evidence their products are safe and that they don’t make misleading claims, though supplement makers typically cite some studies or experts.

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But NeuTherapeutics is going the extra step of drug-style clinical trials to instill confidence in the eventual over-the-counter product, which will be in pill form.

“The reason we are developing a product that’s over the counter that’s both safe and effective, is because women were voting with their feet and getting a product over the counter, so I had to go where women are going,” Brinton said.

Decades of work

Brinton, who earned her undergraduate and master’s degrees from the UA before completing her UA doctorate in neuropharmacology and psychobiology in 1984, has been studying the relationship of estrogen and brain function for decades.

After graduating with her Ph.D. from the UA, Brinton spent four years working as a NIH postdoctoral fellow at The Rockefeller University in New York.

While at Rockefeller observing a clinical trial to determine if estrogen could help treat patients with Alzheimer’s, Brinton befriended a patient who was a psychologist and professor and spent a lot of time getting to know her, walking the campus and chatting.

After returning the patient to her hospital room after a long walk, Brinton said goodbye, closed her door and waited 30 seconds.

“I knocked on the door and entered and asked her, ‘Do you remember me, and she was such a lovely person, she said, ‘I’m so sorry, should I?” Brinton recalled. “And so what she taught me was, it wasn’t that she didn’t remember me, it was that she never encoded me despite the many hours that we had spent together.”

“At the time, I was very focused on understanding how the brain encodes new information, and remembers that information, the molecular basis of that,” she said. “And in that moment, that one woman with Alzheimer’s just transformed the career of this one neuroscientist, and from there, I really began to investigate.”

Alzheimer’s is the most common form of dementia and the sixth-leading cause of death in the United States, affecting nearly 6 million Americans — roughly two-thirds of whom are women.

While the fact that two-thirds of people with Alzheimer’s disease are women is often attributed mainly to the longer average lifespan of women, Brinton is convinced there is a link to the loss of estrogen in the brain during menopause that weakens the body’s defenses.

“It’s because women can start the disease earlier,” she said. “That disease can start in the female brain during the menopausal transition, when there’s a loss of estrogen in the brain.”

Brinton is also a chief collaborator on the Women’s Brain Initiative, an NIH-funded study of how sex differences affect brain aging and risk of Alzheimer’s disease, led by Weill Cornell Medicine in New York.

Brinton said she’s excited about the prospects for NeuTherapeutics and had high praise for Tech Launch Arizona, the UA’s tech-transfer arm, in helping her start the company, which is also a member of the UA Center for Innovation incubator.

“I’m so grateful for the University of Arizona and its technology transfer team is in supporting this, (helping) with all the caveats and all the regulation and adherence to all of the principles and requirements,” she said.

Regeneration study

Meanwhile, the UA brain center and its research partners are still enrolling patients for a Phase 2b clinical trial of its Alzheimer’s drug at the UA brain center, with the support of a $37.5 million federal research grant in 2019.

The drug, allopregnanolone, or allo, is already approved for use to treat postpartum depression, but the UA researchers say it can also promote regeneration of the brain’s neural networks, to reverse the course of the neurodegenerative disease in its early stage.

During a Phase 1 clinical trial, Brinton and her team found that allo, a natural steroid that is already produced within the brain, increased the generation of new brain cells, reducing the formation of beta-amyloid proteins linked to Alzheimer’s and improving cognitive function.

For information on the Alzheimer’s trial, which includes one Arizona site in Scottsdale, go to regenbrain.org.