Sarepta Acquires Rights to CMT Gene Therapy Program from Nationwide Children’s Hospital

Nationwide Children’s Hospital (NCH) has granted the exclusive rights of neutotrophin 3 (NT-3), its gene therapy candidate for the treatment of Charcot-Marie-Tooth (CMT) neuropathies, to Sarepta Therapeutics.

Researchers plan to start a Phase 1 trial for the NT-3 therapy in CMT type 1A (CMT1A) patients next year.

“Gene therapy represents a potential new pathway for the treatment of CMT Neuropathy. We look forward to collaborating with Sarepta, whose dedication to those impacted by neuromuscular disorders and to rigorous scientific exploration, echoes our own at Nationwide Children’s,” Zarife Sahenk, MD, PhD, said in a press release.

Sahenk is the founder of the NT-3 program at NCH, as well as an attending neurologist and director of Clinical and Experimental Neuromuscular Pathology at the Research Institute at NCH and a professor of pediatrics, pathology and neurology at The Ohio State University College of Medicine.

Currently without treatment options, CMT1A is the most common inherited disease affecting the peripheral nervous system.

Schwann cells — found in the peripheral nervous system — normally form the myelin (fatty layer) sheath around peripheral nerves, which provides electrical insulation and improves signal conductance in these nerves.

In CMT1A, the gene that provides the instructions for making peripheral myelin protein-22 (PMP-22) is duplicated, leading to the overproduction of abnormal myelin by Schwann cells and disease-related symptoms such as weakness, muscle atrophy, and loss of sensation.

NT-3 belongs to the nerve growth factor family, meaning it contributes to the growth and survival of neuronal cells in both the central and peripheral nervous systems.

Researchers previously found that an NT-3 gene construct — a lab-made piece of DNA to be introduced in a target organism — promoted nerve regeneration and sensory improvement in a mouse model of CMT1A.

They also dosed eight CMT1A patients with either a placebo or 150 micrograms/kg of NT-3 three times a week for six months.

The four patients who received NT-3 tolerated the treatment well and had significant nerve regeneration compared with the placebo group, which translated to better hand coordination and dexterity. However, due to the small sample size, further research is underway to ascertain potential benefits.

Results were reported in the study, “NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients,” published in Neurology.

More recently, an NCH team led by Sahenk showed that, besides repairing damaged nerves, NT-3 also repairs damaged muscle by increasing muscle fiber diameter and inducing remodeling of fiber types.

“Our agreement today further builds on our strategy to establish a gene therapy engine delivering potentially transformative therapies to treat life-altering rare disease,” said Doug Ingram, Sarepta’s president and CEO.

“CMT, globally the largest inherited neuromuscular disease, is potentially devastating and we are particularly honored to work with Dr. Sahenk, a world-leader in the field of CMT neuropathies, as she prepares to treat patients with CMT type 1A in 2019. Dr. Sahenk has dedicated her professional career, which spans over 40 years, to researching and treating life-limiting neuromuscular diseases such as CMT, Limb-girdle muscular dystrophy, Duchenne and Becker muscular dystrophy. Pursuing this work with Dr. Sahenk exemplifies our approach of success through partnering with the best and brightest gene therapy scientists,” he said.

NT-3 gene therapy also has the potential to treat other subtypes of CMT and other muscle-wasting disorders.