Stem cell therapy for Parkinson’s Disease: Prospects and problems
Parkinson’s Disease is a progressive neurodegenerative disease that develops over many years, leading to impairments of movement and deficits in mental functioning. It affects around 130,000 people in the UK alone, and an estimated 7-10 million worldwide. There is no cure for Parkinson’s, but drugs can effectively treat the symptoms in many patients, and researchers have been working hard over the past 20 years or so to develop stem cell treatments for it.
Anders Björklund of Lund University in Sweden, one of pioneers of using stem cells to treat Parkinson’s Disease, discussed progress in this approach, and the challenges it raises, in a public lecture at the BNA Festival of Neuroscience yesterday.
Parkinson’s is caused by the degeneration of dopamine-producing neurons in the midbrain. These cells regulate movement, and their death leads to the tremors, muscle rigidity and bradykinesia (or slowness of movement) that are characteristic of the disease.
“The challenge is to use stem cells to replace these neurons,” Björklund said. “This will take some time, as we have to understand the biology of stem cells, and what guides repair in the brain.”
The idea is to use stem cells to replace those neurons, and this can be done using several different approaches. One is to dissect the precursors of dopamine-producing neurons from aborted foetuses, and then graft them into the brains of Parkinson’s patients. Upon transplantation, these cells begin to integrate themselves into the existing circuitry, forming connections with other cells.
Various studies show that transplanted cells can survive for many years, and can lead to significant improvement in symptoms. The results are highly variable, however, and some patients benefit from the treatment far more than others. It can be difficult getting enough source material, as between 6-10 donor fetuses are needed for each transplant, and the use of foetal tissue also raises ethical concerns.
One solution is to use induced pluripotent stem cells, which can be generated in large numbers and then reprogrammed into dopamine-producing neurons for transplantation. Typically, it takes about 50 days to generate dopamine-producing neurons in this way. We now know, however, that the cells can be transplanted at an earlier stage and that they continue to mature to form mature dopamine-producing neurons after being grafted into the brain.
Dopamine-producing neurons can now be generated from human embryonic stem cells, too, and these have been shown to significantly improve movement deficits when grafted into the brains of rats with symptoms resembling Parkinson’s. One problem with this approach is that the grafts can become contaminated with dividing cells, and consequently, some of the animals that receive grafts go on to develop tumours.
One of the immediate challenges is, therefore, to make sure the cells are safe and totally free of tumour-forming cells. Another is to identify the best type of cell to transplant – it’s still not clear if embryonic stem cells, induced pluripotent stem cells, or progenitors of dopamine-producing cells are the most effective.
Björklund and other researchers in the field are now trying to make the process of embryonic stem cell differentiation process as efficient as possible, and are further exploring how to reprogram fibroblasts – a type of connective tissue cell found in skin – directly into dopamine-producing neurons.
“The latest clinical trials involve patients at the very early stages of the disease,” says Björklund, “and we think that cell transplants are likely to have a very big impact in these patients.”