November 2013

Researchers identify new potential drug to combat fatal infantile disease

Anil Mukherjee

Researchers at the National Institutes of Health have identified a new potential drug that could help treat Batten disease, a fatal neurodegenerative disease in children. The research team, which included American Society for Biochemistry and Molecular Biology members Anil B. Mukherjee and Goutam Chandra, performed mouse studies that suggest this drug may extend the lives of children with Batten disease. Their findings were recently published in the journal Nature Neuroscience.
Batten disease is a group of rare neurodegenerative lysosomal storage diseases that affect one in 12,500 children. In the infantile type of the disease, children are generally born without symptoms but begin to show psychomotor retardation by the time they’re 11 months to 18 months old, and they’re often blind by the age of 2. These children lose all brain activity and eventually die at around 3 to 5 years old. There is no effective treatment for children with Batten disease.
Children with infantile Batten disease have a deficiency in the PPT1 protein, or palmitoyl-protein thioesterase-1. This deficiency leads to a buildup of waxy substances called ceroids in the cells of many tissues including the brain and eye.
Mukherjee and his colleagues performed a drug screen for derivatives of hydroxylamine, which is known to mimic PPT1 and reduce ceroid buildup but cannot be used clinically due to its high toxicity. They found a derivative called N-(tert-Butyl-Hydroxylamine), or NTBuHA. This compound was effective at significantly extending the lifespan of PPT1 knockout mice without any side effects due to toxicity.
This research team at the Eunice Kennedy Shriver National Institute of Child Health and Human Development also is investigating two additional drugs, known by the brand names Mucomyst and Cystagon, for the treatment of infantile Batten disease patients. Like NTBuHA, these drugs act by breaking down ceroid deposits. The findings are a promising step forward for the treatment of patients with Batten disease, and the researchers hope to begin clinical trials with these drugs soon.

Lymor RingerLymor Ringer earned a Ph.D. in tumor biology from Georgetown University. She is a postdoctoral fellow at Johns Hopkins University.

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