Juvenile batten disease target

The use of PDE4 inhibitors to treat juvenile batten disease

  • PDE4 inhibitors are a novel approach to treat JNCL
  • Demonstrated efficacy using multiple PDE4 inhibitors in JNCL mouse model
  • Preparing IND application for a Phase I clinical study


Licensing Manager: Matt Boehm, Ph.D.
mboehm@unmc.edu or 402-559-2166

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The Use of PDE4 Inhibitors to Treat Juvenile Batten Disease

Tammy Kielian, Ph.D., Professor of Pathology, Dept. of Pathology and Microbiology, University of Nebraska Medical Center

Tammy Kielian, Ph.D.

Researchers at the University of Nebraska Medical Center led by Tammy Kielian, Ph.D., have discovered a promising new treatment that may slow the progression of a deadly child disease, Juvenile Batten Disease.
Also known as Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), Juvenile Batten Disease is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessive mutation in the CLN3 gene that affects one child in every 100,000 live births.
JNCL symptoms usually begin between 5- and 10-years-old. The disease begins with vision loss, leading to eventual blindness. As the disease progresses the children develop seizures, motor loss and cognitive decline.
Unfortunately, there are no treatments for Juvenile Batten Disease, and current therapy merely alleviates symptoms. Children with JNCL typically do not survive beyond the late teens or early 20s.
Dr. Kielian and her team have identified the enzyme phosphodiesterase-4 (PDE4) as a potential target for treating JNCL.
Her lab has shown that microglia in brains of diseased mice are primed to be proinflammatory, produce increased levels of inflammatory mediators and have increased inflammasome activity. They also have shown a reduced expression of molecules critical for astrocyte glutamate regulation such as glutamate transporters and glutamine synthase.
Cyclic AMP is an important second messenger that regulates a variety of signaling events including learning, memory, and neurotransmitter release. Reductions in cyclic AMP negatively impact neuronal homeostasis, promote microglial proinflammatory activity, increase inflammasome activation in macrophages, and reduce glutamate transporter expression in astrocytes.
PDE4 is one of the key regulators of the brain’s cyclic AMP levels, and Dr. Kielian’s group believes that targeting PDE4 will provide a useful treatment strategy for Juvenile Batten Disease.
Dr. Kielian’s lab has tested a number of PDE4 inhibitors,including roflumilast, demonstrating efficacy in the JNCL mouse model.
PDE4 inhibitors significantly improved motor function in diseased mice, attenuated astrocyte and microglial activation, and restored glutamate transporter expression. The drugs were administered daily for six months with no signs of toxicity.
Dr. Kielian working on an Investigative New Drug application for the FDA so she can begin a phase I clinical study.
To discuss licensing opportunities please contact Matt Boehm, Ph.D., at mboehm@unmc.edu or 402-559-2166.