Male birth control research wins audience over at STAT Madness event

What happens when too many excellent, pioneering researchers enter a room? A little madness.

That’s what attendees at the Breakthrough Summit East in New York had on their hands Thursday, as four participants presented their work in this year’s STAT Madness competition — an annual March Madness bracket-style battle to find the best innovation in science and medicine.

The formal bracket competition is still ongoing, but event attendees cast their votes for the fan-favorite “STAT Madness All-Star” award to Lonny R. Levin, a pharmacology professor at Weill Cornell Medicine, for his team’s work to create a new, on-demand birth control option for men.

“I usually am a big skeptic on anything that’s male birth control. But I do actually think the episodic nature of this is really interesting and the mechanism is really interesting,” said STAT’s senior writer and editorial director of events Matthew Herper, who served as one of a handful of “judges” who questioned each presenter. “I’m surprised by how cool I thought it was.”

Levin won the audience vote against competitors who presented research on an alternative to amputation for patients with severe peripheral artery disease, how to get cancer drugs across the blood-brain barrier, and a vibrating pill that can suppress appetite.

The current contraceptive options for cisgender men are severely limited, Levin noted. Men must typically either use condoms, get a vasectomy, or rely on their female partner to take birth control. Levin’s team has performed research in mice for a new potential option: an experimental compound that can stop sperm in its tracks.

Here’s the basic idea: To fertilize an egg, sperm must swim through the vagina up to the fallopian tube. And to do that, they need a gene called soluble adenylyl cyclase, or sAC, which acts like an on-switch that gets sperm tails kicking into action. Researchers found that they were able to knock out sAC and stop the sperm from swimming, first through an injection and then using pills.

“The vagina is actually our partner here,” Levin said. If the sperm can’t swim up into the fallopian tubes, they’ll die in the vagina’s acidic environment. While clinical research is needed in humans, the team’s goal is to create a birth control pill for men that can be taken on demand about 30 minutes before sex and create a window of 12-18 hours of protection from pregnancy while the sperm are incapacitated.

The team is currently testing the contraceptive method in rabbits. But Levin said that a research team separate from his already found two humans who didn’t have the sAC gene and were sterile but otherwise healthy. It’s a good sign the method should work in humans without side effects, but further studies will answer that question for sure.

There are still three more rounds of voting and about two weeks left until the winner of the tournament is determined. Levin’s team is already out of the running for the main title of STAT Madness winner, after being narrowly beaten in the second round by a team at Baylor College of Medicine looking into wastewater monitoring and human viruses.

None of the presenters at Thursday’s event are still in the running for the STAT Madness title, though all of the presentations drew audience interest.

Yulanka Castro Dominguez, associate chief of quality at University Hospitals Harrington Heart & Vascular Institute in Cleveland, presented a new, minimally invasive procedure that can divert blood into healthy veins and out of the narrowed, diseased arteries of patients with severe peripheral artery disease. With this disease, narrow arteries prevent the legs and arms from receiving enough blood flow, causing chronic pain, wounds that don’t heal, and even gangrene. When the disease is severe, about one-fifth of patients have no treatment option except for amputation.

The new technique, called deep venous arterialization, starts at the bottom of a patient’s foot. Surgeons go up into the veins, gaining access to the artery at the top of the leg. Then, with a catheter, needles, and wire, the surgeon essentially builds and connects a new road next to the clogged artery to relieve some of the traffic.

In a study published in the New England Journal of Medicine last year, Dominguez’s team performed the procedure on 104 patients. After six months, three-quarters of those patients who previously had no option but to amputate kept their legs. The team is working now to get longer-term data, Dominguez said. The technique is already FDA-approved for patients who have no other options.

Daniel Heller, head of the Cancer Nanomedicine Laboratory at the Sloan Kettering Institute, presented a new way to attack brain tumors. These tumors are the most common solid tumors in children and the leading cause of cancer-related death in children, he said. That made his research partner, pediatric neuro-oncologist Praveen Raju, ask whether they could use their work on nanomedicines and drug delivery to get nanoparticles across the blood-brain barrier.

“I said no because I want tenure, and the blood-brain barrier is really, really hard to get across,” Heller said. “If you’re a nanomedicine person, this is one way to bang your head against the wall, metaphorically and literally.”

But they tried anyway. The team encapsulated the typically toxic drug vismodegib in nanoparticles that target a specific protein that, in combination with radiation therapy, penetrates the blood-brain barrier. The researchers published a study in Nature Materials last year that tested the new method in mice.

The targeted protein is P-selectin, which shows up outside blood vessels in wounds, infections, and some tumors, similar to the way white blood cells travel the body. And while radiation was needed to activate P-selectin in these tumors, the team believes that the mechanism will be useful against many different types of tumors in all different parts of the body.

“Next? Let’s cure pediatric cancers,” Heller said. But first, they’ll have to make sure the treatment works as well in humans as it did in mice.

And it wouldn’t be a research competition in 2024 without a new potential intervention for obesity. While injectable GLP-1 medications have dominated the conversation around the obesity revolution, a team from the Massachusetts Institute of Technology and New York University has developed a different approach: an electric pill they’ve tested in pigs, which can curb or activate appetite by attaching to the stomach’s mucus lining and vibrating in a way that triggers hormones responsible for regulating digestion and appetite.

It’s “illusory satiety,” said Shriya Srinivasan, an assistant professor at Harvard University who led the research. The device is currently about the size and shape of a large multivitamin pill, she showed the audience. The pigs ingested the pill and then passed it with their digested food.

“So every time you eat a meal, you take it? Wow, sounds scary,” said Xin Zhang, a distinguished professor of engineering at Boston University, winner of the 2023 STAT Madness Summit Audience Pick, and one of this year’s judges.

Zhang’s comment sparked audience laughter. But Srinivasan noted there’s a precedent for ingestible electronics, and this would likely be much cheaper to produce than the current obesity treatments entering the market.

While none of the competitors have a chance to win STAT Madness, many have their sights set on more lucrative goals. (“There’s no prize for winning STAT Madness,” apart from bragging rights, STAT managing editor and judge Gideon Gil reminded the contestants.) Both Heller’s team and Levin’s have formed companies — Selectin Therapeutics and Sacyl Pharmaceuticals, respectively — to continue furthering their work on cancer treatment and birth control.