Eyeing a treatment Searching for a solution for blindness

It was 2002 when Medical University of South Carolina professors Barb Rohrer and Craig Beeson got to talking at a post-seminar dinner at Rita’s on Folly Beach.

Rohrer is a rather intense biologist from Germany, and Beeson is a more laid-back chemist from California, but it turned out they had a shared research interest: the regulation of energy metabolism.

“And so we decided to put our noses together to see what we could do,” Rohrer, 48, recalled during a recent interview.

Fast forward a decade, and that coincidental conversation by the ocean has become a company with promising research on degenerative eye disease and a loyal funding source for years to come. It took a while to get started, but now Mitochem is ahead of schedule in its hunt for the winning molecule.

“We’ve been very lucky,” Beeson, 53, said last month from Mitochem’s new headquarters in the South Carolina Research Authority MUSC Innovation Center on Meeting Street.

There were a number of directions the pair could have taken after that initial conversation, but Rohrer was already researching retinal degeneration in the human eye, so that became the focus.

Specifically, the pair of scientists began to think about how to stall the death of mitochondria in photoreceptor cells known as rods that characterized a disease known as retinitis pigmentosa.

“There’s really nobody in industry that’s even considering going after orphan diseases in the eye,” Rohrer said. “That’s the niche we decided to utilize.”

There were also practical reasons, such as time and money.

While the research might eventually have broader implications, the road through clinical trials is much easier for so-called orphan drugs, those that treat rare diseases. And Rohrer’s longtime patron, Foundation Fighting Blindness, was inclined to continue funding her research.

Late last year, the foundation gave Mitochem a $2 million grant to isolate a lead molecule that could eventually be used in clinical trials. The foundation doesn’t have an equity stake in the company but could be entitled to royalties if the drug becomes viable.

Stephen Rose, the foundation’s chief research officer, didn’t hesitate when asked last month if he thought the Palmetto State pair could really have a vision-saving cure on the way.

“To invest $2 million, yes sir,” he said, noting the foundation’s grant portfolio is $21 million. “Nothing is ever guaranteed, we all know that, but yes, tremendous potential here.”

Retinitis pigmentosa, a relatively rare genetic eye disease, steals a person’s night and peripheral vision bit by bit until only a pinhole of sight remains. “And then you lose that as well,” Rohrer explained. It can strike as early as childhood or much later in adulthood.

“There are no treatments,” Beeson said. “There’s nothing out there. Nobody’s really making any breakthroughs.”

Despite that circumstance, Beeson said, the National Institutes of Health three times denied their requests for funding between 2005 and 2008.

“I prefer to think we were ahead of our time,” Beeson said with a smile.

In May 2008, the foundation came to the rescue, awarding a translational acceleration research grant to MUSC with Rohrer and Beeson as the principal investigators.

That allowed Rohrer and Beeson to buy a “diversity library” of 50,000 organic molecules with drug-like properties and run protein tests on them to see if they could fit the bill.

They narrowed that huge set of possibilities down to 12 molecules by around 2010, and now down to two leading candidates, known as C19H20N2O3 and C21H15N3OS, which have curiously complementary properties.

“Now think about it, you took 50,000 molecules, you screened them, several different assays, and you get two molecules that seem to always work,” Beeson explained. “And then those two molecules, which ... have different internal cores, but when you lay them in space, suddenly they completely overlap in space. You know, the odds of that are like a gazillion to 1.”

“And then you believe that maybe this is right. Maybe this is a real molecule. Maybe there really is a target in the cell that these things are binding to and by doing so it’s improving mitochondrial homeostasis,” Beeson concluded.

The latest Foundation Fighting Blindness grant, which came into Mitochem’s coffers in January, has allowed Rohrer and Beeson to move the chemical part of their research operation to the new Meeting Street lab. The space is intended for exactly these sorts of projects: commercializing research at the university. MUSC owns the patent for the pharmacophore, that is, the molecules and their applications for degenerative diseases, and Mitochem has licensed it.

With the help of Director of Chemistry Chris Lindsey and lab technician Richard Comer, Mitochem set up the labs in March. On April 13, they started the work: making hundreds of derivatives of those two molecules, as many as 20 per week, to maximize efficacy.

Once the molecules are made in the lab, they are tested biologically. Some 700 combinations have been tested on cells — stressed neuronal cells to see if the molecule can help their mitochondria stay alive — and eight have been tested on mice.

It takes two weeks to do the cell tests and about two months to do the animal tests, which are subcontracted to a separate team at MUSC.

Once they have their lead molecule, they can then move on to larger animal testing, such as with pigs at the University of Kentucky or dogs at the University of Pennsylvania.

That will be within the next year or two, and Rohrer and Beeson figure they’re about five years away from a clinical trial. The current grant is to get them to the large animal step, but if they continue to progress, Foundation Fighting Blindness stands ready to fund them to the point of applying to the Food and Drug Administration for a clinical trial.

A lot is riding on this work. There are 50 different genes that could cause retinal blindness, and all involve mitochondrial breakdown, Rohrer explained. Instead of targeting one gene, Mitochem’s solution could counteract many of those gene dysfunctions.

“It’s basically a common target for a very diverse type of a disease,” Rohrer said.

Furthermore, mitochondrial breakdown is symptomatic of many other more common diseases outside the eye.

It will take clinical trials to know for sure, but there are possibilities for much more common debilitating diseases such as Alzheimer’s and Parkinson’s.

Rohrer is still full-time at MUSC, whereas Beeson is part-time, so he can manage the new business. Beeson said running a company is like running a research lab in a lot of ways.

“You’ve got to get money. You’ve got to run your lab. You have to keep your employees happy,” Beeson said, and then you have to sell the science.

Rohrer added that it’s a “bit more risky.”

There’s still a long way to go, but the pair feels good about where things stand.

“I think we’re one of the few, if any, companies that’s got a strategy, that’s actually got molecules, and the molecules that seem to be working,” Beeson said. “That’s why Foundation Fighting Blindness is excited. That’s why we’re excited.”