Veterinary research in Dachshunds paves the way for therapy in children

Researchers from the University of Missouri (MU) College of Veterinary Medicine and School of Medicine, in collaboration with BioMarin Pharmaceutical, have developed a treatment for Batten disease—a rare, fatal genetic disorder that affects children.

Dachshunds also suffer from Batten disease, and currently no effective treatment exists for the disease, which ultimately kills all who are affected. However, the MU researchers have discovered an enzymatic therapy that significantly delays the onset and progression of clinical signs in Dachshunds. The effectiveness of the treatment in dogs has been so encouraging that plans are under way to initiate human trials of the therapy in children.

Dachshunds suffer from Batten disease, a genetic disorder that affects the nervous system. Researchers at the University of Missouri have developed a treatment that delays the onset of clinical signs.

Batten disease affects the nervous system in both people and dogs, causing progressive neural degeneration leading to loss of vision, cognitive and motor function, ability to communicate and, ultimately, death, according to an MU release. A number of different forms of Batten disease exist.

The treatment developed by MU and BioMarin researchers targets a type of the disease that first becomes evident in the late-infantile stage of development. Symptoms for this type of Batten disease begin to appear in human patients around the age of 2.

Batten disease is caused by the absence of an important enzyme within cells of the neural system. This enzyme helps cells break down and eliminate waste proteins. Without this enzyme, cells accumulate waste and are unable to function properly. Martin Katz, PhD, professor of ophthalmology with dual appointments in the MU College of Veterinary Medicine and School of Medicine, along with a number of other MU researchers, worked with Dachshunds affected with Batten disease in a similar way as humans. For their treatment, a therapeutic protein created by BioMarin replaces the deficient enzyme and is directly administered into the spinal fluid once every two weeks. Untreated dogs ultimately succumbed to the disease around 10 to 11 months of age. Dogs treated with the enzyme replacement showed significant delays in the onset of symptoms and survived substantially longer.

"This is an important step toward treating human patients with this debilitating disease," Katz says. "By introducing a replacement for the missing enzyme into the nervous system, we have been able to help the deficient cells eliminate their waste efficiently and slow the disease-related brain degeneration. We believe this treatment approach will be effective in humans as well. Based on research to date, this treatment does not appear to result in a complete cure for the disease, but it could extend the lives and improve the quality of life for those with this form of Batten disease."

"The researchers at MU have painstakingly characterized late-infantile Batten disease in these dogs, and their results indicate a striking similarity in the progression of the disease among dogs and humans," says Charles O'Neill, vice president of pharmacological sciences at BioMarin. "Treatment of the dogs with BioMarin's enzyme replacement therapy has characterized its safety and efficacy and will enable accelerated clinical development of this potential treatment."

Based in large part on the dog studies, BioMarin plans to initiate human trials of the treatment this year.