Breakthrough in tissue transplant

October 25, 1996

Safer and easier transplant treatments for serious degenerative disorders of the nervous system, such as Parkinson's disease and Huntington's chorea, could result from work at Cardiff and Sheffield universities.

George Foster, cell biologist in the school of molecular and medical biosciences in Cardiff, and Bradley Stringer, molecular biologist in the department of oral pathology in Sheffield, have generated immortal neuronal human cell lines, the first reported by any United Kingdom-based team.

This promises to cut demand for live tissue from large numbers of early-aborted foetuses. They also have the answer to a potential problem in any of the new treatments which put cell and tissue transplants into the brain. That problem is that there has to be a means to halt the treatment if harmful side-effects develop.

The purpose of a transplant of this nature is to provide a long-term source of the neurologically active cell products the patient needs to counter his or her illness. In principle, it is no different from conventional "drug depot" therapy, where a slow-release compound is held against the skin in a patch or physically inserted into the body.

But whether they come from primary tissue or cell cultures, transplanted cells spread away from the point of insertion and can never afterwards be entirely removed from the patient's brain or spinal cord.

There needs to be a means of killing the depot cells or stopping them from producing active compounds without harming nearby host cells.

This potential problem has not so far been tackled. By the time sufferers from diseases like Huntington's chorea, who have poor life expectancies after the onset of the illness, begin what is still an experimental treatment, the need to counter the possible adverse side effects is low on anyone's agenda, says Dr Foster. "Neither the Food and Drugs Administration in the United States, nor the Committee on Safety of Medicines in the UK would normally allow a company to market a depot drug which could not be removed in the event of an adverse reaction," he says.

Foster and Stringer immortalised their human cell lines by incorporating within the genetic structure what they describe as an immortalising oncogene, a gene that would normally allow a cell to replicate. It came from the Simian Virus (SV) 40.

SV40 is not inherently harmful to humans. The live virus was accidentally injected into more than 100,000 people in the US and in the UK in the mid-1950s as a result of SV40 being unwittingly included in a batch of polio vaccine.

According to Dr Stringer, one of his Sheffield colleagues was injected with the live virus as a child and has also helped investigate the consequences. There was no demonstrably significant increase in cancers among the recipients.

The first component to providing safety for human recipients of human cell lines immortalised by the use of genetic material from SV40 is a temperature sensitive "switch". Cells reproduce indefinitely below 36OC, but as soon as their temperature is raised to 37OC (normal body temperature) and above, the SV40 oncogene is inactivated and cell replication is irreversibly turned off.

However, the major component of the fail-safe device provides for the ability to remove the immortalised or any other grafted cells from the patient.

They have done this by making the immortal cell line vulnerable to a specific antibiotic which is commonly available but unlikely to be prescribed to sufferers of Parkinson's disease or Huntington's chorea. For patent and publication reasons, full details have yet to be released.

Patients who have been given "fail-safe" injections or transplants of treated cells will have a warning against prescribing this particular antibiotic in their medical records, unless it is to terminate depot therapy.

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