The Niche

Mouse study shows stem cells might help Alzheimer’s

Headlines from a recent PNAS study showing that stem cells can reverse dementia in mice keep popping up in my inbox. Here’s the press release. The cells don’t actually become neurons but instead secrete a well-studied protein called brain-derived neurotrophic factor that stimulates neurons already in the brain to form new connections. The paper from UC Irvine scientists is supposedly out today, but I can’t find it on the PNAS site. I’d like to know how much cognitive performance improved. Also, the researchers used mice genetically engineered to have Alzheimer’s. That’s often the only way to study this, but I’d like to know how well the model represents human disease and also whether te researchers started “treating” the disease pathology long before any clinical signs of the disease became obvious, which would mean the strategy may not work for patients that have had Alzheimer’s for any significant time. Still, it’s cool, and shows that the high, high bar of getting cells to integrate into highly complex tissue may not always be required. (Actually, human trials in the neurodegenerative horror called Batten’s disease are underway with StemCells Inc. The injected fetal neural cells are not supposed to integrate into the brain tissue but to help it destroy a toxin that builds up in diseased patients’ brains. It’s too early to know efficacy yet, but the latest report was that the cells seemed safe.)

In less sanguine news, an autopsy of three Huntington’s patients showed that transplanted neural cells did not survive, and that the transplanted cels degenerated faster than the patients’ own neurons. (I’ll paste the abstract below). Here is a link to this Open Access article as well as a news story from Nature.

Both studies emphasize that not only are techniques fo making specific cell types necessary, but researchers are also going to have to find ways to keep them alive. Compared to the most common animal models, patients are bigger, more complex, and have funcitoning immune systems. As someone recently said of the failure to cure cystic fibrosis in the two decades since the gene was discovered: “we haven’t failed. It’s only been twenty years.”

An autopsy of three human patients who received neural transplants more than a decade ago as a treatment for PNAS paper: Huntington’s disease reveals that the transplanted tissue likely degenerated more rapidly than the patient’s existing neurons. Huntington’s disease is characterized by the loss of specific types of neurons and the production of an abnormal huntingtin protein, which is suspected to play a role in cell death. In an earlier experiment, three patients with Huntington’s disease received transplants of healthy neural tissue to explore whether the grafts could replace damaged tissue. Francesca Cicchetti and colleagues analyzed the brains of these patients posthumously and discovered that the grafted tissue had a shortened lifespan and was equally, if not more, vulnerable to Huntington’s-related degeneration. The authors suggest that their findings raise questions about the therapeutic benefit of neural transplants as a treatment for Huntington’s disease. They propose that alternative treatments for the disease, such as tempering a patients’ immune and inflammatory responses to the huntingtin protein, may provide a treatment paradigm for the disease.

Article #09-04239: “Neural transplants in patients with Huntington’s disease undergo disease-like neuronal degeneration,” by F. Cicchetti, S. Saporta, R.A. Hauser, M. Parent, M. Saint-Pierre, P.R. Sanberg, X.J. Li, J.R. Parker, Y. Chu, E.J. Mufson, J.H. Kordower, and T.B. Freeman


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