The Niche

Transplanted cells detoxify poisoned brain, somewhat

There is some new research just out from StemCells Inc, which is running clinical trials for Batten’s disease, a neuordegenerative disease. Here’s a quick write up from my reading of the paper, a study of a mouse model. Motor coordination symptoms were delayed by a week or so based on a comparison between 14 mice that received transplants and 8 that did not. My initial thoughts are that the length of time of the experiment was too short, and I’m not sure if the magnitude of the observed effect would be clinically meaningful, but it does indicate movement toward ameliorating a serious disease.

Here’s my post from the latest results from StemCells’ Batten’s disease trial indicating that cells survive in human patients for at least a year.

Here’s the mouse research.

Some brains literally poison themselves. In the diseases known as infantile neuronoal ceroid lipofuscinosis or Batten’s disease, brain cells lack enzymes necessary to clear away their byproducts. Clinical symptoms of congenital forms of the disease include seizures, cognitive and motor decline, blindness, and early death. The Palo Alto company StemCells is conducting clinical trials to see whether cell therapy can ameliorate the disease. The rationale is that the functioning enzyme made by transplanted cells can help keep patients’ own cells alive. Work in Cell Stem Cell shows that the transplanted cells do indeed make and secrete the enzyme and that the transplantation delays the loss of motor coordination for a week in a mouse model of the disease.1

Previous, unrelated research had indicated that the transplantation strategy could delay onset of a similar malady called Sandhoff disease for a month and prolong lifespan by six weeks.2 However, this had not been demonstrated for lipofuscinosis nor for the human neural stem cell product the company has developed. A team of scientists led by Nobuko Uchida showed that these cells secreted a functioning lysosomal enzyme palmitoyl protein thioesterase, the enzyme that patients with Batten’s disease lack. Then they transplanted these cells into the brains of immunocompromised mice that were also unable to make this enzyme. When they examined these mice twenty to twenty-seven weeks later, they found that transplanted cells developed into neuronal-like cells in the olfactory bulb, and various types of support cells in other parts of the brain. They remained neural stem cells stem cells in the cortex.

Next, the researchers looked at the amount of lipofuscin, the toxin that builds up in Batten’s patients, in the brains of three mice that received transplants and four that di not. Overall, mice that received transplants had significantly less lipofuscin, 37% less in the cortex, and more than 50% less in the hippocampus.

Thus, the current work shows encouraging proof of principle that transplanted cells can support endogenous ones. According to the paper, evidence from 3,000 mice has not identified any instances of the transplanted cells causing a tumour. The next steps will be to see whether the cells survive long enough and secrete enzyme long enough to have a clinically meaningful effect.

1. Tamaki 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 5, 310–319 (2009) DOI 10.1016/j.stem.2009.05.022

2. Lee, J. P. et al. Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nature Medicine 13, 439 – 447 (2007)


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