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gEnoid therapy slowed rate of decline in children diagnosed with Batten disease, results presented at virtual con 2020joint annual meeting of the International Child Neurology Association (ICNA) and the Child Neurology Society (CNS).

“The treatment’s efficacy and safety were tested in extensive preclinical studies before moving on to the first clinical trial in humans,” said Emily de los Reyes, MD, assistant pediatric neurologist at Nationwide Children’s and professor of clinical pediatrics. and neurology at the Ohio State University College of Medicine in Columbus.

Batten’s disease, or neuronal ceroid lipofuscinosis, is an autosomal recessive lysosomal overload disease, explained Dr de los Reyes. “Nerve cells and other cells of the nervous system are very sensitive to the buildup of wastes such as misfolded or old proteins, lipids and other components of the cell because they are very active,” she said. declared. Neurology today At the Meetings. “The accumulation and lack of removal of these components from cells are hallmarks of all Batten diseases.”

The gene therapy trial focused on Batten disease type CLN6, one of 13 disease genotypes. CLN6-type Batten disease, which is caused by mutations in the CLN6 gene that encodes a protein of unknown function called the CLN6 protein, is characterized by a progressive decline in language, motor skills, cognitive abilities, visual loss and intractable myoclonic epilepsy, explains Dr. dit de los Reyes.

“The onset of symptoms of the late infantile variant CLN6 is about 3 to 4 years old. There is a rapid clinical deterioration in their ability to walk and speak. Most children die in their late childhood or early adolescence, ”she added.

Researchers injected AT-GTX-501, a self-complementary, recombinant, non-replicating adeno-associated virus-9 vector containing the human virus CLN6 gene, in the lumbar spinal cord of children. The patients were followed up weekly for the first month after gene transfer, and every three months thereafter, Dr de los Reyes said.

After 12 months, the 12 children treated with gene therapy experienced a 0.4 point drop in the Validated Hamburg Scale for Motor and Language, compared with a 1.2 point drop observed in the decline in l natural history observed in 16 children who were also diagnosed with CLN6 Batten type disease.

Despite the small number of patients in the study, the difference reached statistical significance (p

At two years of age, eight children treated with gene therapy experienced a functional decline of 0.6 points compared to a projected decline of 2.4 points in the natural history of the disease (p> 0.0001), she says.

“We continue to follow the latest patients on the protocol, which involves monitoring safety and efficacy, in addition to collecting other natural history data, against which we will compare our clinical results,” said Dr. de la Reyes. “The next steps will be informed by this data in the near future.”

This study was funded by Amicus Therapeutics, Inc.

Commenting on the study, Bruce H. Cohen, MD, FAAN, director of the NeuroDevelopmental Science Center at Akron Children’s Hospital and professor of pediatrics at Northeast Ohio Medical University, noted how devastating the disease is to people. children and their families. “These children are healthy in their first few years of life, but then develop regression in cognitive and language skills, behavioral changes and seizures, followed by sleep disturbance and vision loss. Death usually occurs in the early teens. ”

Dr Cohen, who was not in the study, said the disease usually occurs by inheriting a mutation from each parent in the CLN6 gene, which is found on chromosome 15. He noted that the vector could be used to treat only one form of the disease.

The study aimed to find out “the safety and efficacy of this gene therapy,” he said. “Using a scale of motor and language functions, the eight children [out to 24 months] treated with gene therapy had a considerably slower rate of disease progression compared to the natural history of 16 children treated before this therapy was available.

Five patients had adverse events, four of which had side effects possibly related to treatment (vomiting, fever and abdominal pain), and all four children recovered, he noted.

“These are preliminary results, and it is very encouraging that the therapy has benefited the patients,” he said. “There is a lot of work to be done, and questions such as whether earlier treatment can provide greater benefit is still not known.”

Dr de los Reyes has received grants and consulting fees from Amicus and Biomarin. Dr. Cohen had no relevant disclosure.

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CNS-ICNA PL67: de los Reyes E, Meyer K, Lehwald L, et al. Single Dose AAV9-CLN6 Gene Transfer Stabilizes Motor and Language Function in Batten Disease CLN-6: Interim Results from First Gene Therapy Clinical Trial.

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