When Erik Nelson, MD, got word in 2012 that he had been awarded his very first patent, he did not pop the champagne cork. The UC Mood Disorders Center psychiatrist, who was honored with other patent recipients at a recent UC men’s basketball game, admits it was a “cool feeling” to receive a patent. But any inclination to celebrate was tempered by reality. Like many ideas in science that lack sponsors, grants or the potential for large profits, the patent has been stuck in limbo, in a kind of patent purgatory.

“It’s not uncommon for ideas not to go forward,” Dr. Nelson says. “Not because they wouldn’t potentially work, but because the funding isn’t there or the timing isn’t right.”

Dr. Nelson’s patent is a “use patent” for histamine H3 receptor antagonists, including betahistine, as a treatment for atypical depression. Dr. Nelson has postulated that betahistine could help people with atypical depression by reversing one of the characteristics of their disorder – a dampened cortisol response to stress. But whether betahistine actually would convey such benefits is unknown, because no drug company has stepped forward to underwrite a clinical trial.

Dr. Nelson, Associate Professor of Psychiatry and Behavioral Neuroscience, shares the patent with UC colleague Floyd “Randy” Sallee, MD, PhD. While Dr. Nelson views H3 receptor antagonists as a potential treatment for atypical depression, Dr. Sallee views them as a potential treatment for ADHD.

Dr. Nelson arrived at his idea while he and two other colleagues were studying stress response in two subtypes of depression: melancholic and atypical. People with melancholic depression often have elevated levels of the stress hormone cortisol. They tend to sleep poorly and lose their appetite. People with atypical depression, in contrast, appear to feature a blunted hormonal stress response, with lower-than-normal cortisol levels. They tend to be sluggish and to eat and sleep too much.

“Most anti-depressants have been shown to lower cortisol levels when they are excessively high in depression,” Dr. Nelson says. “It isn’t known whether they can reverse the blunting of the cortisol stress response that we saw in our study of patients with atypical depression.”

That observation prompted Dr. Nelson to start looking at existing drugs, either FDA-approved or investigational, that had the effect of boosting the stress response. “We didn’t have evidence, but I started thinking, if these individuals have a blunted stress response, maybe something that raises the stress response would be helpful. It might give them more energy and reduce their appetite.”

Dr. Nelson zeroed in on histamine, a neurotransmitter that helps regulate sleep, appetite, and alertness but had not been studied with regard to mood. The early anti-histamine drugs, as many allergy sufferers will remember, made you sleepy and lethargic and could also stimulate appetite. Those drugs worked by blocking a histamine receptor (H1). Dr. Nelson was looking at their opposite: histamine H3 receptor antagonists, which are thought to work by “removing the brakes on histamine” and allowing more of it to be released in the brain.

In particular, Dr. Nelson was interested in betahistine, a drug that was already approved almost everywhere in the world as a treatment for vertigo. The drug has a special status in the United States. Although not FDA-approved, it is on a list of drugs that can be prescribed if the ingredients are shipped here in bulk and then compounded into a capsule at a pharmacy.

Dr. Nelson submitted an investigational new drug (IND) application to the federal government, got approval to have the drug shipped from China, and ensured that the drug could be compounded at the UC College of Medicine. But as he worked to clear these hurdles, time marched on. His major research grant expired, and took on additional clinical duties to support his salary.

When the patent was finally awarded, Dr. Nelson was no longer working on the project. Nevertheless, he had new hope that a drug company would license the patent idea.

“It would be fun to resurrect this project,” he says, “to bring it back from purgatory.”

– Cindy Starr