Treatment for juvenile neuronal ceriod lipofuscinosis

Unmet Need

Juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, is one of the most prevalent pediatric neurodegenerative disorders which occurs with a frequency of between 2 and 4 in 100,000 live births. It starts at around 4 years of age and it is characterized by blindness, seizures, motor and cognitive decline, and early death. JNCL is caused by mutations in the CLN3 gene. The CLN3 protein (CLN3p) harbors a galactosylceramide (GalCer) lipid raft binding domain and participates in the transport of GalCer from Golgi to lipid rafts in the cell membrane. GalCer content of lipid rafts is important for healthy neurons as it is involved in Schwann cell-axon interactions, oligodendrocyte differentiation and transduction of signals across the myelin membrane. In CLN3-mutant cells, CLN3p with ineffective GalCer binding fails to traffic GalCer to lipid rafts. This alters physiochemical properties and structure and impacts function of the rafts. As a result, CLN3-deficient cells grow slowly and have enhanced sensitivity to apoptosis thus contributing to the neurodegeneration underlying the JNCL disease. To date, JNCL is fatal, and only supportive therapies for it are available. Therefore, finding a treatment for this disease is of critical need.

Technology

Duke researchers have developed methods for treating JNCL associated with CLN3 deficiency in a patient by supplementing them with an effective amount of GalCer. The treatment has been successfully tested in animal trials, and on cell samples donated by the affected children and their families.

Advantages

• Halts or delays progression of JNCL disease
• Prolongs patients’ lives, improves the quality of life.
• Ready to be tested in human trials