Substantial improvement was achieved in a mouse model of Batten disease, a rare, hereditary neurodegenerative disease, after transplantation of normal human neural stem cells. The study showed that the transplanted stem cells provided a critical enzyme that was missing in the brains of the experimental mice and represent an important step toward what could be a successful therapeutic approach for this currently untreatable and devastating disease.

Image: Graphic of stem cells giving birth to new neurons in the hippocampus.

Infantile neuronal ceroid lipofuscinosis (INCL), commonly known as Batten disease, is a fatal neurodegenerative disease in children caused by a mutation in the gene that makes a crucial enzyme called palmitoyl protein thioesterase-1 (PPT1). A deficiency of PPT1 in the brain causes the abnormal accumulation of a cellular lipid storage material called lipofuscin, which leads to neuron death, a decline in cognitive and motor skills, visual impairment, seizures and premature death. It’s nearly impossible to get the PPT1 enzyme into the brain, making intravenous enzyme replacement therapy an unviable treatment approach.

It has been hypothesized that transplanted donor cells might be able to secrete the needed enzyme directly into the host brain. Researchers have developed a mouse model of INCL that mimics many aspects of the human disease and provides an excellent experimental model for testing whether a human neural stem cell transplant may be a beneficial disease treatment. Dr. Nobuko Uchida led a study that tested this hypothesis with banked human neural stem cells that had been purified, expanded, and preserved.

"We took a novel approach and transplanted normal, nontumorigenic, and nongenetically modified human neural stem cells to deliver the deficient enzyme in the mouse model of INCL," explains Dr. Uchida. "We transplanted self-renewing human neural stem cells because, theoretically, these transplants can provide life-long production of the missing enzyme." Dr. Uchida and colleagues found that the purified human neural stem cells engrafted to the brain of INCL mice, migrated extensively, and produced enough PPT1 in the host mice to elicit significant improvement. Specifically, the INCL mice exhibited reduced lipofuscin, widespread neuroprotection, and a delayed loss of motor coordination.

"Early intervention with neural stem cell transplants into the brains of INCL patients may supply a continuous and long-lasting source of the missing PPT1 and provide some therapeutic benefit through protection of endogenous neurons," concludes Dr. Uchida. "These data support our rationale for continued development in humans and the potential for a medical breakthrough in this deadly disease."
References:
1. Nobuko Uchida, et al. Neuroprotection of Host Cells by Human Central Nervous System Stem Cells in a Mouse Model of Infantile Neuronal Ceroid Lipofuscinosis. Cell Stem Cell, Volume 5, Issue 3, 310-319, 4 September 2009. doi:10.1016/j.stem.2009.05.022.

Add comment

User Name (Required)

E-mail (Required - Never shown publicly)

Website (Optional)

Notify me of follow-up comments

If you cannot read the code click to refresh for a new code.

Add comment

Cancel