Maria Corina Roman, a 40-year-old Danish surgeon, underwent a breast cancer operation in 2001. Two years later she suffered a serious relapse and doctors declared she had just a year to live.

But Roman chanced upon the news that China had approved gene therapy for the treatment of cancer. Without hesitation, she headed to Shenzhen in early 2004. She was willing to give gene therapy a go at least to try to prolong her life.

"I am still living and working in my job as a surgeon in the hospital," said Roman in an e-mail written this month to Peng Zhaohui, chairman and CEO of Shenzhen SiBiono GeneTech Co Ltd.

The company's Gendicine is the world's first commercially available gene therapy treatment.

Roman is one of a growing number of patients to benefit from gene therapy, which has drawn increasing attention among medical professionals and the public.

Gene therapy

Gene therapy treatment is based on the theory that many serious diseases are caused by genetic dysfunction, either by inheritance or postnatal mutation. Cancer, diabetes and haemophilia are typical diseases caused by genetic dysfunction.

Since research on gene therapy started in the early 1980s, it has been enthusiastically embraced by scientists and doctors. So far, more than 1,100 gene therapy plans are in the process of clinical trials worldwide, mainly in the United States. More than 60 per cent of the trials target cancer treatment.

Gendicine uses an adenovirus as a vector to convey a p53 gene into tumour cells. The treatment is generally called gene addition.

Jack Roth, of Houston-based MD Anderson Cancer Centre of the University of Texas in the United States, was the first scientist to discover in rats, and then human beings, that the p53 gene is a tumour suppressor. In other words, the p53 gene normally stops the formation of tumours. More than 60 per cent of cancers are related to the dysfunction of p53 genes.

Adenoviruses are a group of viruses that cause conjunctivitis and upper respiratory tract infection.

When the adenovirus infects tumour cells, the p53 gene it carries will be added to the genome of the tumour cells. The growth of those harmful cells should therefore be suppressed.

In the 1980s, gene therapy became a hot topic for research. By the late 1990s, a group of gene therapy medicines had been approved for the third stage of clinical trials.

But in 1999, 18-year-old Jesse Gelsinger, an American high school student who had a rare genetic disease, died during clinical trials of a gene therapy four days after receiving an injection of the medicine.

His death, widely reported by the media, alerted the public to the potential risks of gene therapy. As a result, the US Food and Drug Administration (FDA) and its European and Japanese counterparts adopted a highly cautious attitude in evaluating and approving clinical trials of gene therapies.

Since then, most treatment trials have been put on hold. In this context, the approval of Gendicine in October 2003 by the State Food and Drug Administration (SFDA) in China was a stimulus to gene therapy research worldwide.

Zhang Shanwen of the Beijing Tumour Hospital has been the leading doctor overseeing clinical trials of Gendicine.

Between 2001 and 2003, 107 patients with late-stage head and neck squamous cell carcinoma tumours underwent eight weeks of a joint treatment of radiotherapy and weekly gene therapy injections. Among them, 68 patients, or 64 per cent, have experienced complete regression and 39 have experienced partial regression.

In November this year, the SFDA approved H101, the oncolytic adenovirus-based gene therapy.

The drug uses a genetically modified adenovirus that is able to dissolve cancerous cells to replicate and kill tumour cells.

"The approval of the two gene therapies in China is really an encouraging phenomenon," said Roth on the sidelines of an ISCGT conference in Shenzhen. "It makes the world's gene therapy practitioners perceive their promising future.

"I don't mind who commercializes my invention. What matters is that patients elsewhere are benefiting from the invention," he added.

Gendicine

Although Gendicine's commercialization is stimulating advances in gene therapy, some scientists have asserted that a looser regulatory environment in China has led to the approval of Gendicine and H101.

A scientist at the China branch of the Danish drug giant Novo Nordisk, who refused to be identified, said: "The fact that China approves the world's only two commercialized gene therapies while no other country does so makes us question whether the country might not have done enough scientific evaluation."

But Peng refuted the allegation.

"China has long adopted a highly cautious practice that it would not approve any new drug not approved by the US FDA. The approval for Gendicine is a result of our carefully designed product, the delicate clinical trial plan, the availability of huge patient resources and the low costs of doing clinical trials," Peng said.

This position was echoed by Sang Guowei, director of the National Institute for the Control of Pharmaceutical and Biological Products, at the ISCGT conference.

Sang is a former deputy director of the SFDA and his institute is the major evaluation agency of the SFDA dealing with new drugs.

According to Sang, China has followed the practice of the United States and Europe and adopted very strict criteria for evaluating gene therapies.

To approve gene therapy in China, regulators have to evaluate the therapeutic gene, the delivery vehicle, the delivery system and method, and the in-vitro study efficacy data.

Also, pre-clinical animal studies include toxicity safety and efficacy data, and the clinical trial investigation plan includes safety and efficacy studies, an overview of the production process, an overview of quality control, the discussion of the novelty of the product, and the discussion of a product commercialization strategy.

"China's clinical trial practice and regulation are credible, and we have no reason to doubt the efficacy of the country's gene therapy research," said James Norris of the Medical University of South Carolina and the president of ISCGT.

Since Gendicine was approved, Peng and his team have launched more research, extending the medication to patients suffering from lung, liver and stomach cancers, Peng told China Daily.

Also, more patients are involved in the Phase-IV clinical trial of Gendicine.

"In accordance with the State regulation on innovative drugs, our drug does not need a clinical trial-IV, but we will try to do such trials to collect more clinical data," Peng added.

So far, more than 3,000 patients have been treated with Gendicine, including 400 cancer sufferers from outside China and 500 for clinical trials. Doctors chairing clinical trials nationwide have reported obvious progress in patients' tumour regression and survival time.

(China Daily December 27, 2005)