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Friday 20 March 2008

EMBARGO LIFTED on Monday 24 March at 5am AEDT

RAPID ROUNDUP: Therapeutic cloning treats Parkinson's disease: Nature Medicine - Experts comment.

Therapeutic cloning has been used to treat Parkinson’s disease in mice in a report published in Nature Medicine. This is the first time cloning has been used to successfully treat any disease in the same subjects from whom the cells were derived. In therapeutic cloning, the nucleus of a cell from a donor subject is inserted into an egg with the nucleus removed (also known as somatic cell nuclear transfer (SCNT)). This cell then develops into an embryo from which stem cells can be harvested for therapeutic purposes.

The stem cells in this case were turned into the neurons which are missing in Parkinson’s disease. The mice that received cells derived from their own clones improved. But when these cells were grafted into mice that did not genetically match the transplanted cells, the cells did not survive and the mice did not recover.

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Professor Richard Boyd is Deputy Director of the Monash Immunology and Stem Cell Laboratories, Victoria

“The technology of being able to induce stem cells is now looking much more realistic. This is the first functional demonstration that the cells produced can be used to treat a condition, in this case Parkinson’s-like disease. They also showed that it was a self specific effect because when they transferred the cells into another donor they were rejected. This is very much a proof of concept that one can create one’s own stem cells to potentially treat a patient specific disease.

The necessary underlying provisos are that the effects were still highly variable, the process still inefficient, and there is no information on long term safety issues and all these concerns would have to be satisfied before there is any thought of transferring this to the clinic. This is an exciting step down the pathway of creating a self specific stem cell and getting away from the ethical demands of traditional embryonic stem cells."
Associate Professor George Mellick is a Parkinson’s disease expert at the Eskitis Institute for Cell and Molecular Therapies at Griffith University, Qld. He is also Vice-President of Queensland's Parkinson's Disease Society (Parkinson's Queensland Incorporated) and is an invited member of the Experts Advisory Panel for Parkinson's Australia.

The data shows that engineered embryonic stem cells, derived from an adult animal with experimental parkinsonism and cultured into dopamine-producing cells, can be transplanted back into the animal to improve the symptoms. This is the first time that this kind of autologous transplantation has been done with ES-derived cells. Proponents of adult stem cells would claim that their cell lines are much more amenable to such autologous transplantation without the need for somatic cell nuclear transfer.

Are people with Parkinson’s disease any closer to a cure? Unfortunately, not really. That cell transplantation can improve animal parkinsonism has been known for a long time. While it does show promise as an alternative means to treat the motor symptoms of human Parkinson’s disease, like our currently available medications, the emerging cell transplantation approaches don't address the diverse degenerative changes that occur in multiple regions of the brain seen in human Parkinson's disease. The idea that we may be able to re-generate complex brain circuitry is, in my opinion, still some way off.”

Professor Bob Williamson is Chair of the National Committee for Medicine, Australian Academy of Science and is Professor of Medical Genetics, University of Melbourne

“The Sloan-Kettering group in New York, headed by Lorenz Studer, has shown that stem cells that are made from skin cells can be used to treat a mouse model of Parkinson disease and are not rejected by the immune system.

The stem cells were made using a technique known as 'therapeutic cloning', or somatic cell nuclear transfer, where the nucleus of a cell from a mouse (or, in principle, a patient with Parkinson disease or any other disorder) is pushed into an egg from which the nucleus has been removed. The so-called 'embryo' (though it should be noted that many ethicists, including myself, do not believe this is an embryo) is then grown to a point where embryonic-like stem cells can be isolated.

In each case, the mouse that donated the nucleus from its skin cell was then made to suffer from Parkinson disease (it should be noted that the model, although often used, is not exactly the same as the human disease). When stem cells made from the same mouse using therapeutic cloning were injected into the key part of the mouse brain for Parkinson disease, the striatum, the mice that received matched transplants got better. While not “cured” from Parkinson disease, they were clearly improved compared to mice that received cells that were not therapeutic clones.

Studer has shown that therapeutic cloning works, at least for mice. However, mice are not men, and no one has yet succeeded in obtaining a stem cell line using somatic cell nuclear transfer for humans, though everyone is sure that, however inefficient, this will come soon. Mice are also inbred, which makes rejection less likely even with cell donors that are not “identical”. Nonetheless, this represents an advance, because it has been shown that stem cells can be made by therapeutic cloning and are not rejected, and can cure a model of a human disease in mice. It also underlines how foolish those people are who oppose nuclear transfer; cells in a test tube are not an embryo, and these experiments could give great hope to those with Parkinson disease, type 1 diabetes and cystic fibrosis.”

Professor Jack Martin is John Holt Fellow and Emeritus Professor of Medicine at the Bone, Joint & Cancer Uni, St Vincent's Institute, Victoria.

“The whole game has changed so much now with the new way of reprogramming adult cells, the induced pluripotent stem (iPS) cells, that this work, such as it is, is pretty well out of date and no one will ever try and repeat it. It doesn’t really show anything we didn’t already know: that you can prepare embryonic stem (ES) cells and program them towards dopamine production and get a partial improvement when you put them into immune deficient mice. These same authors showed it a few years ago, one of their references, Barberi et al., with therapeutic cloned cells. In fact, in that paper they compared them with ordinary embryonic stem cells that weren’t therapeutically cloned and they found no difference. So basically, it’s all out of date now and the paper itself has got so many flaws that it’s really not especially exciting.”

Wendy Rogers is Associate Professor in Medical Ethics and Health Law at Flinders University, South Australia.

“This research appears to show that there is significant therapeutic potential using embryonic stem cells created by somatic cell nuclear transfer (SCNT), known as therapeutic cloning. The main ethical issues raised by this process are to do with the creation of embryonic stem cells and the potential for benefits (or harms) to patients treated with embryonic stem cells.

Therapeutic cloning requires access to large numbers of human eggs. In this process, the interests of women must be protected. Issues to consider are harms to women through ovarian hyper stimulation, potentially coercive pressures such as financial inducements, informed consent and regulatory oversight. Collecting ova in non-paternalistic ways that are acceptable to women overcomes one of the main barriers to SCNT.

SCNT and therapeutic use of embryonic stem cells requires destruction of embryos. There are two important differences between embryos created for procreative purposes and those created by SCNT. Firstly, the potential for embryo to grow into a healthy human baby is relatively large for embryos created by union of sperm and egg but very small for embryos created by putting an adult nucleus into egg cytoplasm. The intention is also important, in assisted reproductive technologies embryos are typically created for reproductive purposes and have the genetic potential to grow into new and unique human beings, whereas SCNT embryos are created for research aimed at developing therapeutic applications, are not implanted, and often do not have a new and unique human genetic complement.

The potential to benefit patients is brought one step nearer with this research. This is an exciting development if SCNT opens up the way to new therapeutic procedures that benefit patients."