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A Novel Treatment for Cats Provides Hope for Humans

February 1, 2016

Debbie Nicholau volunteering with the Red Cross after Hurricane Sandy

Debbie Nicholau volunteering with the Red Cross after Hurricane Sandy

As an American Red Cross volunteer, Deborah Nicholau drove an emergency response vehicle across the country to help victims of Hurricane Sandy in 2012. She spent three weeks feeding people in New York and helping in any way she could, all while hiding her pain from a disease that left blood on her pillow when she woke in the morning.

Nicholau suffers from oral lichen planus, a chronic oral inflammatory disease that creates ulcers in her mouth and makes it painful to talk and eat. Stress compounds the situation, which is why the disease flared while she was providing emergency aid on the East Coast.

“It was embarrassing as well as painful,” she said. “I’d wake in the morning, wondering how to explain this to my colleagues who were in the same hotel room.”

The trouble started after Nicholau underwent gastric bypass surgery in 2011. Before the surgery, Nicholau had been receiving gamma globulin infusions for various immune system disorders. Afterwards, her doctor was reluctant to continue the therapy due to side effects. That’s when the oral lichen planus appeared. Not only is the disease painful, it also places patients at greater risk for developing oral squamous cell carcinoma (independent of other risk factors such as smoking and alcohol consumption).

“There’s a high level of anxiety associated with the illness because of the cancer risk,” Nicholau said. “And the ulcers on my lips look nasty—people think you have herpes—I feel like I have to explain I’m not contagious. This disease is demoralizing, scary, painful and just no fun. It affects every aspect of my life.”

Nicholau’s partner, Linda, acknowledges that the illness affects their relationship.

“It’s uncomfortable to know that kissing my partner is painful for her,” she said. “We have to be creative about showing affection.”

Less than one percent of the population are afflicted with this largely unexplored disease, according to Dr. Nasim Fazel, a board-certified dentist and dermatologist with the UC Davis Health System. But those patients are drawn to the Oral Mucosal Disease Clinic in the Dermatology Department where Fazel specializes in treating oral mucosal diseases, thanks in part to her background in dentistry.

“We have a significant proportion of patients that don’t respond to available treatments, which puts them at greater risk for oral cancer as a result of poorly controlled disease,” Fazel said. “Many patients are told they have no treatment options at all. These people are desperate and will go to great lengths to find treatment and seek relief.”

Translating Veterinary Medicine to Human Medicine

While there is no cure for oral lichen planus to date, there is hope—in the form of a novel treatment for a similar disease that affects cats.

Fazel was attending a medical conference when she came across a presentation on regenerative medicine by researchers from the UC Davis School of Veterinary Medicine. Dr. Boaz Arzi, a veterinary dental surgeon—in collaboration with Dr. Dori Borjesson, a veterinary pathologist, and Dr. Frank Verstraete, also a veterinary dental surgeon—had started a clinical trial investigating a novel stem cell therapy to treat feline chronic gingivostomatitis (FCGS). The oral disease in cats is analogous to the disease found in humans; both are T-cell immune mediated illnesses.

“I was really excited to hear about their work because the cat disease behaved very similarly to what I saw in my human patients with oral lichen planus,” Fazel said.

Cats with FCGS often undergo a full-mouth dental extraction and several courses of corticosteroids and antibiotics; however, even that drastic approach doesn’t always cure the disease.

The UC Davis trial included cats whose disease was not resolved by tooth extraction. The veterinary researchers developed a technique to take fat-derived stem cells taken from the cats, process the cells and give them back intravenously, with the goal of lowering inflammation and promoting tissue regeneration. (The study was initially supported by a grant from the school’s Center for Companion Animal Health.)

“FCGS is a challenging disease to treat, but we were frustrated that some cats wouldn’t respond to traditional treatment,” Arzi said. “We were banging our heads against the wall and this stem cell therapy was a last resort.”

Luckily for many of the cats in the study, this regenerative medicine approach worked. Within a few months, they were living a normal life, free from pain and disease. Results from the clinical trial recently appeared in the journal Stem Cells Translational Medicine and are the first to demonstrate the safety and efficacy of treating a naturally occurring, chronic inflammatory disease in cats with their own fresh, fat-derived stem cells. The study also identified a potentially useful biomarker that could determine if cats will respond to stem cell treatment in general (as not all do).

“We’re the first researchers to come up with this patent-pending technique for any mammals, including humans,” Arzi said.

In fact, the researchers involved formed a company, InnovoSTEM, in collaboration with the UC Davis Venture Catalyst Program to explore the potential of this technique.

Hope on the Horizon

As a naturally-occurring animal model of disease, FCGS may also serve as a useful model for the treatment of human oral inflammatory disease—in an method increasingly known as a One Health approach. Based on the success of this study in cats, Fazel (who was a co-author on the journal article) recently submitted a grant to establish a human clinical trial to use mesenchymal stem cell therapy to treat oral lichen planus in humans.

Fazel has been working collaboratively with the veterinary medicine team to perform comparative studies between histopathologic characteristics and blood inflammatory biomarkers of FCGS and various chronic oral inflammatory conditions such as oral lichen planus, aphthous stomatitis and vesiculobullous diseases.  

“We’re in desperate need of novel therapies to treat chronic inflammatory mucosal disorders such as oral lichen planus, which are chronic, challenging to treat and of major impact to patients’ quality of life,” Fazel said. “Having this opportunity to translate what we’re learning in veterinary medicine to human medicine and working together to bring therapies discovered in the cat model to chronic oral inflammatory diseases in humans is exciting and has great potential.”

Nicholau uses oral xylocaine to deal with the pain of oral lichen planus and help her eat, but the numbing factor means she can’t taste her food. It’s really important to get proper nutrition after gastric bypass, she said.

She has tried numerous treatments and prednisone, but that resulted in gaining 40 pounds. While those treatments may help bring a flare up under control, the side effects are nasty, so Nicholau is back to taking immune globulins through an IV line several days a month, a procedure which takes five hours.

“This puts me out of my volunteer work a good week out of the month—that’s important time for me. It gives me confidence and self-esteem; it’s my outlet,” Nicholau said. “I was in the nursing field for 20 years. I’m used to working with people and giving back to my community. This disease has crimped my style completely.”

But she’s excited to hear about the possibilities that veterinary medicine has brought to human medicine.

“I just hope it brings new treatment soon,” she said.

Related press release

Trina Wood, Communications Officer; 530-752-5257