It’s worth noting that the exciting paper in Nature Medicine is grabbing headlines not so much for the advance in Parkinson’s disease but because it is the first time that cells derived from cloned embryonic stem cells have been used to ameliorate disease. In the Nature Medicine paper from Sloan-Kettering’s Viviane Tabar and Lorenz Studer and others, researchers report that cells survived much better and mice’s symptoms improved if they were transplanted with genetically matched neurons.

For those of you coming back from Easter weekend to see Monday’s headlines, Nature reported on this story on Friday, making it harder to find now. Here it is . Other reports come from Bloomberg and the Guardian. And just to keep things in perspective, here’s a report of a non-stem cell breakthrough in Parkinson’s in mice based on research published in Nature just over a year ago.

Coincidentally, another news outlet reports on a poster presentation of using autologous bone-marrow derived cells in Parkinson’s patients. This hasn’t gone through the rigorous vetting process like the publication, but here is the summary of that work.

In the Nature Medicine paper from Sloan-Kettering’s Viviane Tabar and Lorenz Studer and others, researchers report that cells survived much better and mice’s symptoms improved if they were transplanted with genetically matched neurons. Matched neurons were made by taking nuclei from cultured mouse skin cells, placing the nuclei into eggs to create an early-stage embryo, and then destroying the embryo to make embryonic stem cells.

In fact, in some mice receiving non-matched neurons, no transplanted cells could be found. Also, the brains of mice receiving non-matched neurons showed several signs of an immune attack. Thus, the results indicate that immune rejection could be a big barrier in cell therapies.

It’s worth noting that these mice had Parkinsonian symptoms because the researchers’ killed brain cells in otherwise normal mice. There are many, many questions that will need to be answered before such work is transferred to the clinic, and a relatively late question will be on the therapeutic power of transplanting cells derived from people who got Parkinson’s naturally. The mice were observed for 11 weeks after transplantation before their brains were examined.

London’s Science Media Centre sent out some commentary to reporters concerning the paper, and I thought this analysis attributed to Robin Lovell Badge was interesting:

“This is a very well conducted study that provides further proof-of-principle of the idea of “therapeutic cloning” using a mouse model. The cloning technology was used to derive Embryonic Stem (ES) cell lines specific to individual mice with Parkinsons disease.

Dopamine-producing neurons obtained from these cell lines were then grafted back into damaged brains of the mice where they led to significant amelioration of Parkinsons symptoms. These “autologous”

grafts worked much better than heterologous grafts where the dopamine neurons were put into unrelated animals. This in itself is important as it had been thought that the brain was largely an “immune-priveleged site” (i.e. a site not seen by the immune system), but it is clear that the heterologous cells were attacked by the immune system. This would help explain some of the poor results in human clinical trials using grafts of midbrain cells obtained from aborted fetuses, as these would have been heterologous.

“The authors were also able to test several independent ES cell lines corresponding to individual mice, and could show that most seemed to work well. This is very encouraging as it indicates that the cloning process is a sufficiently robust method of reprogramming cells back to an early embryonic state, at least when the early embryos are used

to derive ES cell lines. There was substantial variation in the

numbers of cells found in the grafts, but this seemed to be animal-to-animal variation and generally not a cell line problem.

“In a few animals the authors noticed overgrowth of undifferentiated neural cells. This is a problem that requires more research, in particular to derive ways of eliminating immature cell types.

However, the authors did not detect any teratomas (a type of tumour containing many different cell types), which is very important as it suggests that they succesfully eliminated any undifferentiated ES cells during their in vitro differentiation protocol. This is again very encouraging, although the authors only waited 11 weeks post graft for the analysis and it would have been better to have left some animals much longer. Leaving them for longer would also have allowed a better test of functional recovery and whether this was really stable.

“Ideally one of the next steps will be to repeat the whole procedure with a monkey model, in which all the individual steps have now been established. This will allow much better tests of functional recovery and safety.”