March 23, 2008

breakthrough in Parkinson’s disease research

The Science Media Centre found experts to comment on new research on mice, published in the journal Nature Medicine, that raised the possibility of using brain tissue cultivated from cloned cells to treat Parkinson’s disease.

Dr Kieran Breen, Director of Research and Development at the Parkinson’s Disease Society, said:

“Stem cell therapy offers great hope for repairing the brain in people with Parkinson’s. It may ultimately offer a cure, allowing people to lead a life that is free from the symptoms of Parkinson’s.

“The aim of stem cell therapy in Parkinson’s disease is to replace the dead dopamine-producing nerve cells with new, healthy cells. This will restore the supply of dopamine within the brain and allows it to work normally again.

“Scientists have already shown that stem cells can be grown in the laboratory. However, one of the many technical challenges scientists need to overcome, before stem cell therapy can become an effective treatment for people with Parkinson’s, is ensuring that cells produce dopamine neurons that survive after transplantation.

“Researchers have already investigated the potential of using human embryonic stem cells derived from nerve tissue for Parkinson’s stem cell research, but the majority of these dopamine producing cells died after being transplanted into animal models of the condition.

“The Sloan-Kettering group in New York has been the first research group to demonstrate that it is possible to make dopamine-producing nerve cells by using the genetic material taken from an animal’s normal cells to form stem cells. These were then used to make nerve cells that were transplanted into the same animal to treat the symptoms of Parkinson’s. This is an exciting development, as for the first time, we can see that it may be possible to create a person’s own embryonic stem cells to potentially treat their Parkinson’s. However, cells that were transplanted to other animals died.

“Researchers in this area now need to carry out more studies to satisfy safety concerns and to make the process more efficient before these studies are carried out on people living with Parkinson’s.”

Professor Robin Lovell-Badge, Head of Genetics Division at the MRC National Institute for Medical Research, said:

“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 Parkinson’s 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 Parkinson’s 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-privileged site’ (ie 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 successfully 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.”