RegenxBio Expands Pipeline with Gene Therapy for Form of Batten Disease

Rare Daily Staff

RegenxBio said it is developing an experimental gene therapy known as RGX-181, for the treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, one of the most common forms of the rare, progressive and fatal condition Batten disease.

CLN2 disease is a neurodegenerative lysosomal storage disorder caused by mutations in the TPP1 gene. Mutations in the TPP1 gene, and subsequent deficiency in TPP1 enzymatic activity, result in the accumulation of metabolic waste in cells throughout the body including the brain and retina. CLN2 disease is characterized by seizures, rapid deterioration of language and motor functions, cognitive decline, loss of vision and blindness, and premature death by mid-childhood. Onset of symptoms is generally between two to four years of age with initial features of recurrent seizures, language delay, and difficulty coordinating movements.

There is currently no cure for CLN2 disease. Current treatment options include palliative care or enzyme replacement therapy that uses recombinant TPP1 delivered to the ventricles of the brain through a permanently implanted device on a biweekly basis.

RGX-181 is being developed as a novel, one-time treatment for CLN2 disease utilizing the NAV AAV9 vector to deliver the gene encoding for TPP1, the enzyme deficient in children with CLN2 disease. Following a single administration given by injection into the brain ventricles RGX-181 treatment is designed to modify cells in the CNS, thereby providing a durable source of TPP1 and allowing for long-term correction of cells throughout the CNS.

In an animal model for CLN2 disease, treatment with RGX-181 has been shown to restore TPP1 activity to levels greater than those in non-affected animals, and to improve neurobehavioral function and survival. The extent of CNS correction observed in animal studies suggests that RGX-181 has the potential to be an important and suitable therapeutic option for patients with CLN2 disease.

“Our NAV technology platform holds tremendous promise for advancing this new product candidate in our neurodegenerative disease pipeline,” said Olivier Danos, senior vice president and chief scientific officer of RegenxBio. “CLN2 is a rapidly progressing, fatal disease with limited treatment options and no cure. Children with CLN2 disease experience an array of serious symptoms such as seizures, deterioration of language and motor skills, blindness, cognitive decline and premature death. The goal of our RGX-181 clinical program is to develop a single-dose treatment to halt progression of neurological decline and improve a broad range of these devastating symptoms experienced by children with CLN2 disease.”

RegenxBio expects in 2019 to apply to the U.S. Food and Drug Administration to initiate clinical trials for RGX-181. The company also has gene therapies in development for MPS I and MPS II, both lysosomal storage disorders with CNS involvement.

August 30, 2018
Photo: Olivier Danos, senior vice president and chief scientific officer of RegenxBio