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Collie-like dog on the beach with a big stick
Dogs with a form of epilepsy that doesn’t respond to current medicines could be successfully treated thanks to a new drug therapy from the School of Veterinary Medicine’s center to combat chemical-threat agents. (Maureen Simons)

In Helping With Canine Epilepsy, Center to Combat Chemical-Threat Agents Learns About Treating Humans

By Trina Wood on February 5, 2018

Epileptic seizures — in dogs or people — can be frightening to witness. In either species, the seizure stems from a neurological disorder and manifests in loss of consciousness with involuntary jerking or twitching of limbs, vocalization, drooling, chomping and sometimes involuntary urination and defecation.

While there are some treatments for dogs with chronic epilepsy, there is still a subset of canine patients that doesn’t respond to currently available medications. But hope for a new therapy is on the horizon from a somewhat surprising source — the UC Davis CounterACT Center of Excellence, a federally funded program to combat chemical-threat agents.

Dog seizure research stems from 9/11 terrorist attacks

“The terrorist attacks on 9/11 served as a huge wake-up call for the United States,” says Pamela Lein, a developmental neurobiologist and neurotoxicologist in the UC Davis School of Veterinary Medicine who also serves as the center’s director.

“They really showed us that we’re not prepared as a nation for treating civilian mass casualties involving chemical-threat agents.”

Congress funded the CounterACT program through the National Institutes of Health. It supports researchers working with animal models to come up with better therapies for treating victims of chemical exposure.

Center studies seizure-inducing chemicals

Lein explains that the center’s research is relevant to epilepsy and to other types of seizures because they study seizure-inducing chemicals — in particular organophosphates and tetramethylenedisulfotetramine.

Organophosphate compounds are typically found in pesticides, jet fuel and as additives in paints and other products. They are also used in nerve agents such as soman and sarin — deadly chemical warfare compounds used in recent terror attacks in Syria.

Tetramethylenedisulfotetramine is a powerful neurotoxin once used as a rat poison and now banned in most parts of the world.

Used rats to understand seizure-inducing chemicals

(In the video animation above by Doug Rowland, researcher with the Center for Molecular and Genomic Imaging, a revolving rat brain shows via micro computerized axial tomography imaging how it calcifies from an epileptic seizure several weeks after exposure.)

In the first five years of working with the CounterACT program, Lein says they spent a lot of time characterizing the pathology caused by these seizure-inducing chemicals in rodent models.

Thanks to the use of advanced imaging techniques such as positron emission tomography or PET scans, and magnetic resonance imaging or MRI, at the UC Davis Center for Molecular and Genomic Imaging, researchers were able to see what was happening in a rodent’s brain in real-time during a seizure and in the days, weeks and months following the seizure.

“The activity in the rodent brain during and following chemical exposure is very similar to what’s been seen in humans and animals who have status epilepticus [a condition in which epileptic seizures follow one another without recovery of consciousness between them],” Lein says. “So, this basic science has implications for improving human and animal health.”

She is now working with some of the school’s neurology faculty — Pete Dickinson, Beverly Sturges, Maggie Knipe and Karen Vernau — on the steps needed to design and launch a veterinary clinical trial for dogs with chronic epilepsy that don’t respond to other types of medication.

Chronic seizures are a common clinical problem

Head shot of a shaggy dog
This new drug therapy could prolong the life of dogs with chronic epilepsy who don’t respond to treatments currently available.

“Chronic seizures in dogs are a common clinical problem in veterinary medicine and can severely affect the quality and length of the patient's life, especially in dogs that don’t respond well to medications,” says veterinary neurologist Maggie Knipe.

“We know that epileptic dogs are good models for seizure disorders and treatments in humans, and having novel therapies as options for these patients will dramatically increase our ability to provide exceptional, state-of-the-art care.”

A dog lover herself, Lein is excited about this possible application of a therapeutic lead developed in her lab. Before they can launch a clinical trial though, the researchers have to ensure the safety of the drug.

“We hope to have the safety data in the next six to 12 months and get underway with the clinical trial,” she says. “Within a couple years, we may have data to show whether this new therapy is effective for dogs.”

And eventually, the hope is that the therapy ­­­works for humans.

Trina Wood is the UC Davis School of Veterinary Medicine’s communications “Jill of All Trades,” a lover of animals who tells multimedia stories.