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Promising Gene Replacement Therapy for Niemann-Pick Type A Disease Moves Forward at Ohio State

Research led by Krystof Bankiewicz (photo), MD, PhD, who recently joined The Ohio State University College of Medicine, shows that gene replacement therapy for Niemann-Pick type A disease is safe for use in nonhuman primates and has therapeutic effects in mice. These research findings were published online on August 21, 2019, in the journal Science Translational Medicine. The article is titled “Adeno-Associated Viral Vector Serotype 9–Based Gene Therapy for Niemann-Pick Disease Type A.” Prior to joining Ohio State as a Professor of Neurosurgery, Dr. Bankiewicz conducted this translational gene therapy research at the University of California at San Francisco, in conjunction with researchers in New York, Massachusetts, and Spain. Niemann-Pick disease type A (NPD-A) is a lysosomal storage disorder characterized by neurodegeneration and early death. It is caused by loss-of-function mutations in the gene coding for the enzyme acid sphingomyelinase (ASM), which hydrolyzes sphingomyelin into ceramide. With this disease, the body's ability to metabolize fat within cells is affected, causing these cells to malfunction and, eventually, die. This inherited disease can affect the brain, nerves, liver, spleen, bone marrow, and lungs. The three main types of Niemann-Pick disease are types A, B and C. The signs and symptoms experienced depend on the type and severity of the condition. Some infants with type A will show signs and symptoms within the first few months of life. Those with type B may not show signs for years and have a better chance of surviving to adulthood. People with type C may not experience any symptoms until adulthood. Dr. Bankiwicz and fellow researchers evaluated the safety and effectiveness of adeno-associated viral vector serotype 9 (AAV9)-based gene therapy. Using a newly developed cerebrospinal fluid delivery method into a specific area of the brain allowed widespread gene expression in the brain and spinal cord of nonhuman primates without signs of toxicity.

In addition, the treatment provided a “bystander effect” by preventing motor and memory impairment and increased survival in a mouse model of the disease, said Dr. Bankiewicz, who also is a member of Ohio State’s Neurological Institute.

“This is the ‘proof of concept’ of gene therapy in animal models for this disease. It’s a big jump in the development process as we work toward one day being able to safely give this therapy to children who otherwise would die by age 3,” Dr. Bankiewicz said. “Our plan is to translate this exciting data into human clinical trials at The Ohio State University Wexner Medical Center within the next couple of years.”

Based on this research, Dr. Bankiewicz and his team, including co-author Lluis Samaranch, PhD, an Assistant Professor of Neurological Surgery at Ohio State, will move forward with additional animal studies in preparation to eventually begin clinical trials in humans.

“Dr. Bankiewicz is a world leader in neuro-restorative medicine – particularly gene therapy. With his recruitment here – along with the expertise of his five-member research team he’s bringing with him – The Ohio State University College of Medicine is making a strong commitment to developing a gene therapy program to develop treatments for this and other diseases, such as Parkinson’s and Alzheimer’s,” said K. Craig Kent, MD, Dean of Ohio State College of Medicine.

Throughout his career, Dr. Bankiewicz has maintained a strong focus on the development of translational approaches to drug, gene, and cell replacement therapies.

His research has focused on new treatments of serious diseases, including brain cancer, Parkinson’s disease, Huntington’s disease, Alzheimer’s diseases, pediatric neurotransmitter deficiency, and lysosomal storage disorders. At Ohio State, Dr. Bankiewicz will work closely with the Department of Neurological Surgery to conduct other gene replacement therapy clinical trials in humans.

Dr. Bankiewicz has co-founded MedGenesis Therapeutix Inc., Voyager Therapeutics Inc., and Brain Neurotherapy Bio Inc, and also invented several devices currently used clinically to administer gene therapy to the brain.

[Press release] [Science Translational Medicine abstract]