When it comes to federal funding for medical research, Wyoming scrapes the bottom of the barrel. But much of the research taking place in the Equality State could change the world.

In 2017, Wyoming pulled in $14.1 million from the National Institute of Health, widely known as the biggest funder of medical research. The figure made it the least awarded state for NIH funding, with only a handful of states even in the neighborhood.

Idaho pulled in $15 million, Alaska brought $16.4 million, and North Dakota got $21 million. From there, the numbers start to get a lot bigger quickly. At the opposite end of the scale for comparison, California locked down $4.2 billion in funding that same year, making Wyoming’s research dollars look like a rounding error.

Still, according to United for Medical Research – a “coalition of leading research institutions, patient and health advocates, and private industry” advocating for continued increases in NIH funding over time – the biopharmaceutical industry in Wyoming supports 156 businesses and 934 jobs in the state.

NIH isn’t the only game in town, and some Wyoming startups fund their research through traditional venture capital. Through the Biotechnology Innovation Organization, a large trade association representing biotechnology companies, academic institutions, state biotechnology centers and others, Wyoming brought in $15 million in venture capital investments between 2014 and 2017. And, in general, the bioscience industry had 38% higher wages than the rest of the private sector at an average annual salary of nearly $71,000.

Despite the relative smallness of the field in Wyoming, some companies are working on things that could be big – world-changing big. And if the drugs and processes they’re working on ever get green-lit by the Food and Drug Administration after that lengthy and astronomically expensive approval process, they’ll extend lives while also improving the quality of life for those affected.

Healing peripheral nerve damage

Jared Bushman is an assistant professor of pharmaceutical science at the University of Wyoming. In 2014, Bushman came to the state from Rutgers University. He arrived at a lab that couldn’t get his research for healing peripheral nerve damage over the finish line.

“When I came here, it became apparent the lab space wasn’t equipped to do the types of research I needed,” he told the Laramie Boomerang in 2016.

Between 2014 and 2016, he and the school worked to get a new lab in place that could help him test his hypotheses on animals – pigs, in this instance. The funding for the lab came through donations from the ALSAM Foundation, and opened up the world of nerve damage to his research team.

It’s a big world affecting a lot of people. Every year, between 500,000 and 1.2 million surgeries addressed at repairing peripheral nerve damage occur, Bushman said. And according to the National Institute of Health, more than 20 million Americans have some form of peripheral neuropathy, and that’s considered a low estimate.

“The peripheral nerves are like the cables that connect the different parts of a computer or connect the internet,” NIH wrote on its website. “When they malfunction, complex functions can grind to a halt.”

That can mean complete disabilities or mild annoyances, but all people with peripheral nerve damage suffer from some quality-of-life issues. And surgery is the only real fix. Problem is, Bushman said, that surgery requires grafting in another nerve. That means many patients sacrifice one function to save another.

For example, he said, someone who has lost motor control in their forearm, disabling hand usage, might be willing to sacrifice control or feeling from elsewhere to get that usage back.

“They would fillet open the back of their calf, pull out another nerve and cut that into a segment corresponding to the length of the nerve missing,” Bushman said. “They see partial motor control as a trade-off for losing feeling in part of their leg. That’s the best they can do.”

And since the nerves aren’t quite the same functionally, regaining partial motor control is a best-possible outcome. However, there’s a known better way – allografting. Where grafting uses a similar nerve from the same body, allografting uses the same nerve from a donor’s body.

But nerves from donors go unused, currently. Donor implants like this require body-wide immunosuppression. Drugs administered to heart transplant patients, for instance, suppress the immune system in its desire to attack and eliminate the new organ, which it registers as a threat instead of a life-preserving implant. While experts see shutting down the entire immune system as an acceptable risk and expense for preserving quantity of life, it generally won’t happen for quality-of-life issues.

“It’s too much expense [and risky],” Bushman said. All it would take is a simple mosquito bite to introduce what could be a deadly pathogen to someone on immunosuppressive therapy, he said.

That’s the gap where Bushman’s research is reaching for something better. In June, Bushman started up Localis, a business aiming to commercialize local immunosuppression. Like localized anesthesia, it can be delivered only to the area that needs it, curbing the need to knock out a person’s entire immune system for an allograft. He applied for his first patent and, in 2018, landed a patent with a jargon-laden abstract.

“Embodiments described herein relate to restorative solutions for segmental peripheral nerve (PN) defects using allografted PNs for stimulating PN repair,” the patent stated. “More specifically, embodiments described herein provide for localized immunosuppression (LIS) surrounding PN allografts as an alternative to systemically suppressing a patient’s entire immune system.”

Did you glaze over a bit reading that? You’re not alone.

“When I started into bioscience, I fell asleep in meetings because I think I understood about one in three words,” Bushman said.

His research has been funded in part by the Department of Defense, where nerve damage is more common than other professions. He’s seeking a continuance on the research through that line, but said he’ll never know for sure until the check arrives.

And even if research can continue, there’s a $50 million to $100 million path to commercialization through FDA clinical trials.

“We think we have something that’s extraordinarily effective,” he said. “But there are so many things to go.”

Halting Parkinson’s, ALS and other neurodegenerative diseases

Moving to the northwest corner of Wyoming, scientists in Jackson are looking at ways to combat neurodegenerative diseases like Parkinson’s and Alzheimer’s.

Jackson-based startup Nitrome Biosciences continues working on a novel treatment for Parkinson’s disease that could halt its inexorable progression and create a multibillion-dollar enterprise.

“No one’s going to reverse Parkinson’s disease,” said Nitrome’s founding scientist, Irene Griswold-Prenner, in an interview with Wyoming Business Report in 2018. “But we will halt it.”

That confidence has already led to closing funding on two seed rounds, with an upcoming Series A on the horizon to really get going, if all continues to go well through the seed rounds.

“Everything’s going almost as well as it possibly could,” Griswold-Prenner said in a phone interview.

Her young team’s efforts have gone into identifying an enzyme that seems to be tied to neurodegeneration so they can then develop drugs to inhibit it.

“It is everything we could have hoped for in terms of something we think is interesting and potentially druggable for Parkinson’s,” she said. “This is a new area of biology that no one had any awareness even existed.”

Her team is identifying new things about the enzymes at least on a weekly basis, and so far everything points to it being directly related to the disease, meaning blocking its progress won’t have deleterious effects on the person being treated. Instead, it will stop the disease however far it progressed, leading to greater quality of life for people battling Parkinson’s, ALS, fibrosis and possibly even cancer.

“I always knew we would identify this enzyme,” she said. “My only fear was we don’t want to inhibit that. But it looks good for inhibiting and that we’ll be able to develop compounds that will inhibit it.”

Is it batty?

But she’s not the only Jackson-based researcher on the task. In a nondescript building in Jackson bedecked with a carved wooden bear holding beakers next to vaguely Teton-shaped mountains, Brain Chemistry Labs is also working toward a novel drug treatment. The treatment, like Nitrome’s, focuses on the $220 billion problem of Alzheimer’s, Parkinson’s and ALS that affects more than 6 million Americans.

And like Griswold-Prenner with Nitrome, this nonprofit is also seeking a novel way to treat the neurodegenerative diseases. While Big Pharma has thrown billions at the problem to try to break it down with brute force, it’s been a black hole, founder Paul Cox said in an interview with Fortune magazine.

“Each trial is a billion bucks; each targets the same thing,” he said in the magazine. “None have worked. It seems to me that if you’d put in a billion bucks and failed, you’d say, ‘Let’s try something else.’”

In 2017, the FDA approved a Phase II ALS trial with L-Serine, a naturally occurring amino acid Brain Chemistry Labs say can slow disease progression in enrolled patients.

And the nonprofit has done it with a roughly $2 million annual budget absolutely dwarfed by Big Pharma’s footprint in the game.

“Rather than investing in brick-and-mortar and establishing a large, bureaucratic organization, the Institute for Ethnomedicine (Brain Chemistry Labs’ former name) has created a virtual model by inviting world leaders in the appropriate disciplines to perform key components of our research,” a whitepaper published by the nonprofit stated.” This collaboration is not only unique, but very efficient and effective in rapidly advancing the research unencumbered by bureaucracy. It incorporates an innovative blend of novel discovery, exceptional human capital and a singular mission to move from cause to cure.”

The research led the nonprofit to remote islands with a concentration of Lou Gehrig’s disease, or ALS, 100 times higher than normal. What they found caused a reexamination of a once-rejected theory.

BMAA is a toxic amino acid that Brain Chemistry Labs postulates can trigger these illnesses in genetically vulnerable people. It occurs naturally throughout the world. During Brain Chemistry Labs’ testing, it attacked nerve cells and introduced neurodegenerative symptoms in monkeys.

And in the island communities they study, like Guam, indigenous people ate flour produced from a seed bearing the toxin as a regular part of their diet. But studies dropped off on the lead when they found it would take literally a ton of flour per month for the toxin to take root.

Because of that history, Fortune pointed out that Brain Chemistry Labs has been a target for derision, as well as praise. But Cox wondered if another food source could magnify the toxin, leading him to study the diets of the indigents again.

Turns out that they self-identified as the hunters of flying foxes – a bat they hunted right into extinction. While the older generations contracted the neurodegenerative symptoms, the next generation that missed the feast of flying foxes didn’t seem to be contracting it.

Their team tested museum specimens of the bat and found high concentrations of BMAA, as well as in the brains of indigents who died of neurodegenerative conditions – and in Alzheimer’s patients in Canada. It wasn’t present in the minds of those who died of other causes.

A long path

While each of these researchers has a potentially world-changing hypothesis or treatment, each has a long row to hoe before the world can ever reap the benefits.

Other states bring in literally billions in research dollars, while most of Wyoming’s researchers are left to cowboy up and find their own funding. The lion’s share of research dollars pours from the NIH to the University of Wyoming.

But researchers like Nitrome, Brain Chemsitry Labs and, to a lesser extent, Localis are attempting to fund cures and solutions unlike the world has ever seen.

Only time will tell where it all leads.

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