Seattle-based Targeted Genetics announced last week it had halted the PhaseI/II study of its investigational gene therapy for the treatment of inflammatory arthritis after one of the trial subjects died.

"Even though the cause of the illness wasn't known, and is still uncertain, the agency immediately placed the trial on clinical hold - meaning no further product can be administered and no new patients can be enrolled," the US Food and Drug Administration (FDA) said in a statement last week.

The FDA said that the drug tested uses an adeno-associated virus (AAV) vector to deliver the gene encoding for tumor-necrosis factor receptor (TNF-R) - a key mediator of inflammation in arthritis - directly into the joints.

More than 100 subjects have been enrolled in the trial, according to the Targeted Genetics, and since it started in October 2005 no similar serious events have appeared.

Overall, 55 subjects have received two doses of active drug, which is what could have triggered the deceased patient's serious adverse event (SAE), as he became sick after a second gene-therapy injection into an arthritic joint.

However, the biopharma company stressed that a link between the death and the injection of the second dose of the therapy cannot be made until there is further research is conducted.

"The clinical course that this individual experienced has, to our knowledge, never been seen as a consequence of exposure to AAV vectors or naturally occurring AAV. We continue to work closely and diligently with the FDA and the study's independent Data Safety Monitoring Board to determine the cause of the SAE as quickly as possible," said H. Stewart Parker, chief executive officer of Targeted Genetics.

The FDA said it was investigating to determine whether the illness was relalted to the treatment. At the moment, specific details about the death are not available.

"The investigation into the cause of the patient's illness and subsequent death is intensive and ongoing," said the FDA.

In addition, the regulatory body said that as a precautious measure it is also reviewing all ongoing trials involving any use of AAV.

At the moment, there are currently around 30 gene therapy trials conducted in the US using AAV as a delivery method.

AAV vectors are increasingly used by researchers in gene therapy delivery as they usually induce a very low immune reaction in patients.

They efficiently deliver genetic information to specific cell types and can be engineered to carry a variety of DNA sequences. In addition, AAV vector particles are stable; the vector genomes persist in cells for extended periods of time, and do not integrate into chromosomal DNA, according to Targeted Genetics.

However, researchers found that mice injected with a type of adeno-associated virus developed cancer and an article describing the study was published last week in Science.

The gene therapy field, once believed to have the potential to change the face of medicine, has suffered several blows since its heyday in the early 90s.

In 1999, Jesse Gelsinger, an 18-year-old with a rare metabolic disease who was participating in an experimental gene therapy at the University of Pennsylvania died of a strong immune reaction to the treatment.

It appears that there is a link between between this case and the Targeted Genetics trial. The University of Pennsylvania trial was led by Dr James Wilson, who was also owned a private company called Genovo. The firm licensed the technology used in the clinical trial and Targeted Genetics acquired Genovo in 2000 for $66m in stock, according to media reports.

However, Targeted Genetics was not available for comment at the time of publishing.