New cells for old in Parkinson's trials

Cells from aborted foetuses are being used to treat diseases of the nervous system. Michael de Laine reports on a controversial therapy.

Patients suffering from Parkinson's disease may soon receive a combined replacement and protective treatment if research collaboration between Lund University in Sweden and a Danish biotech company bears fruit. Over the past 20 years, researchers headed by Anders Bjorklund of the Wallenberg Neuroscience Centre at Lund University, have pioneered the treatment of Parkinson's by nerve-cell transplantation, initially in rodents, then humans.

Dopamine-rich nerve cells originating from embryos and aborted foetuses are implanted in human brains via small holes drilled in the cranium. The implanted cells bind to the patient's own cells, replacing degenerated cells. Investigations indicate that Parkinsonism does not affect the new brain cells. The 250 severely ill Parkinson's patients who have received replacement foetal nerve cells in clinical trials in various countries are said to experience pronounced improvement.

But cells from as many as ten foetuses are needed for one treatment, in part because only about 10 to 20 per cent of the cells survive. "There is also a limited supply of embryonic and foetal brain cells, and it is difficult to ensure standardised quality," Bjorklund says.

"We are working on ways to cultivate these cells artificially in large numbers so we no longer need to use nerve cells originating directly from foetuses," says Teit E. Johansen, director of NsGene, the Danish company collaborating with Wallenberg. The artificially cultivated cells will initially be produced at NsGene in western Copenhagen. They will be immortalised, which means that a stable cell line can be developed from a single cell.

The replacement therapy is used when patients have so few nerve cells left that traditional drug treatments have no effect. NsGene, which hopes to commercialise the Parkinson's treatment, believes it could be combined with a protective therapy to prevent further nerve cell deaths and help the remaining nerve cells retain full functionality. The patients can then be treated with conventional medicine.

NsGene emerged from a research and development programme at another Danish biotech company, NeuroSearch, where Johansen is head of molecular pharmacology.

The programme aimed to develop new, genetic, therapeutic ways to treat diseases of the central nervous system, such as Alzheimer's and Parkinson's diseases. About 2 million people around the world suffer from Parkinsonism.

Researchers at the Danish company identified and cloned a new neurotrophic factor called Neublastin. This has a protective and growth-promoting effect on the nerve cells that degenerate in Parkinson's patients. The protective therapy would be used on patients showing initial symptoms of Parkinsonism.

The NeuroSearch findings, resulting patents and the research group itself were transferred to NsGene, in which Sweden's Karolinska Investment Fund also has a stake.

Johansen believes that using Neublastin in co-transplantations with foetus nerve cells can give a cell survival rate of about 60 per cent. This implies a large reduction in the number of aborted foetuses needed for each treatment.

Bjorklund sees a three-year perspective for clinical trials using the neuro-protective approach in combination with foetal cell implants, before market launch four years later. The time-scale for implantation using artificially cultivated cells is longer, as cell development is not sufficiently advanced to provide the necessary documentation before clinical trials on humans.

NsGene is not the only Danish company cultivating brain cells. Medi-Cult, which has specialised in the development of cell-cultivation methods, is collaborating with ReNeuron, based in London, on a similar project.

ReNeuron coordinates a European consortium in a project called Ectins (European Cell Therapy in the Nervous System), aimed at finding commercially viable ways of deriving and delivering conditionally immortalised brain-stem cells for transplanting into diseased brains. Once injected, these cells migrate to the site of damage and replace the injured cells with healthy ones of the same type, thus effecting repair. Conditionality means the cells will divide in tissue culture but not when implanted into the brain.

The replacement treatment is ethically problematic, Bjorklund admits. "Implanting embryonic cells is a controversial therapy, as the source of the cells is destroyed human material."

Niels M. Johansen, of the Danish Centre for Ethics and Law in Nature and Society, says the question most often raised is whether using cells from aborted foetuses reduces the human being to an inanimate source of spare parts for biological material.

Sweden has allowed cells to be taken from aborted foetuses for some years, but not Denmark. The Danish Council of Ethics has not yet formulated a policy in this area.