Researchers led by a team at Rosalind Franklin University of Medicine and Science have devised a new therapeutic approach to treating a rare but deadly neurodegenerative genetic disease in children. The study, published this week in Nature Medicine, addresses the urgent need to discover treatments for Batten disease, a fatal neurodegenerative disorder affecting up to four of every 100,000 children in the United States. The disease has no cure, and treatment options are few.

Professor Michelle Hastings, PhD, director for RFU’s Center for Genetic Diseases, led the study in collaboration with researchers at Ionis Pharmaceuticals and Sanford Research. Published July 27, “Therapeutic Efficacy of Antisense Oligonucleotides in Mouse Models of CLN3 Batten Disease” demonstrates that symptoms in rodent models with the disease can be treated through the application of antisense oligonucleotides (ASOs) designed to attach specifically to the CLN3 gene product disrupted in CLN3 Batten disease. The researchers also demonstrated that human cells cultured from patients with the disease respond to treatment in a manner that indicates a reversal of cellular defects.

“When rodents were treated with the therapeutic CLN3 corrector, their lifespan was extended, motor skills improved and waste buildup in the brain was lessened,” said Dr. Hastings. “It was a surprising demonstration that partial correction of the defective CLN3 gene can lead to meaningful improvements in an animal model with this disease.”

“Our work tested a novel approach to therapeutically target the expression of the most common cause of the disease using ASOs — directed to the mutated form of the gene,” said graduate student Jessica Centa, leading author on the paper. “These results are a critical step toward our long-term goal of developing a treatment for CLN3 Batten disease."

The FDA has approved a number of antisense-based therapeutics for genetic diseases in the last few years, including spinal muscular atrophy, another pediatric neurodegenerative disorder. The number of genetic diseases is estimated at more than 7,000, and most have few if any effective treatments. ASO technology offers a potential therapeutic answer to this problem.

“We have work to do before this therapeutic will be ready to test in humans, but the animal studies suggest that our approach may provide an effective treatment in patients,” Dr. Hastings said.

Dr. Hastings was recently awarded a $2.3 million grant from the National Institute of Neurological Disorders and Stroke to advance the team’s investigation into correcting faulty gene expression associated with CLN3 Batten disease using antisense oligonucleotide technology. ASO is a therapeutic platform with potential applications for a large number of inherited genetic diseases. The grant was awarded in collaboration with colleagues in the Pediatrics and Rare Diseases group at Sanford Research, Sioux Falls, SD, led by neuroscientist Jill Weimer, PhD. 

The Center for Genetic Diseases is one of six disease-focused centers within RFU’s new Innovation and Research Park that are driving the translation of novel medical discoveries through expanded collaborations with industry and biotech entrepreneurs.

“Dr. Hastings’ latest NIH grant is an acknowledgement of her team’s seminal work to find therapeutic options for a devastating pediatric neurodegenerative disease and also RFU’s strong culture of collaboration, innovation and mentorship,” said Executive Vice President for Research Ronald Kaplan, PhD. “We look forward to the advancement of this study, which offers hope for a healthier future to so many children and their families.”