Medicine's wild east

South China Morning Post

It's a stem-cell therapy untested and unproven for many 'incurable diseases, but in the mainland's little-regulated system, hospitals are cashing in on the last-chance hopes of the desperate and the dying

By Fiona Tam in Qingdao
Updated on May 17, 2011

The Singaporean doctor has ALS, the incurable degenerative disease of the nervous system. He tried the drug with the best chance of slowing the weakening of his muscles, the compromising of his respiratory system, the steady onset of death. But he is allergic. He figured he had only one hope left.

Dr Poon Lee Kwee, 61, joined the droves of foreigners now flocking to mainland hospitals for stem-cell treatments — therapies that are untested and unproven, but in the mainland's little-regulated climate, are offered far more freely than in the US and other Western countries.

Seven months after being diagnosed with amyotrophic lateral sclerosis (ALS), the general practitioner paid the equivalent of HK$155,420 for a month-long therapy in Guangzhou in March. Poon received six injections of mesenchymal stem cells (MSCs), a kind of adult stem cell from umbilical-cord blood at Guangdong Provincial Hospital of Traditional Chinese Medicine.

The treatment has undergone no clinical trials, yet the hospital's website claims that a wide range of conditions considered incurable by other means are now treatable with its revolutionary stem-cell therapy — from the fatal ALS, cerebral palsy, autism, Parkinson's disease, spinal-cord injuries, and optic-nerve disorder to foot ulcers caused by diabetes.

But there is no convincing evidence published in any reputable journal to support MSCs as a treatment for diseases like these, said Marius Wernig of Stanford University in California.

For the hospital's claims to come true "would be a miracle", Wernig, principal investigator at Stanford's Institute of Stem Cell Biology and Regenerative Medicine, said.

Unlike embryonic stem cells — which in theory give rise to all the body's stem-cell types — tissue-specific stem cells such as MSCs are limited in their potential and largely make the cell types found in the tissue from which they are derived, according to the US-based International Society for Stem Cell Research. Therefore, it's impossible for a single adult somatic stem-cell type to treat multiple unrelated diseases such as diabetes and Parkinson's disease.

Stanford Stem Cell & Regenerative Medicine Institute director Irving Weissman , told reporters last year that stem cells from umbilical cords did have a very limited capacity to make scar, bone and fat. "But they don't make brain, they don't make blood, they don't make heart, they don't make skeletal muscle, despite what various people claim," he said.

The injections' maker, Shenzhen-based Beike Bio-Technology says the treatments are offered by more than 50 mainland hospitals. Chairman Hu Xiang said its stem cells, mainly extracted from umbilical cord blood, had been injected into more than 10,000 foreign patients from 70 countries. He said only 2.8 per cent of patients had slight side effects such as fever or headache. Hu refused, however, to disclose a success rate.

Hua Qing, Beike's coordinator in the Guangdong hospital, concedes the injection can't actually cure serious diseases, but can "improve" patients' conditions to some degree.

That claim isn't based on medical data, but on patients' testimonials — something that the International Society for Stem Cell Research (ISSCR) warns others to be wary of.

A month after getting the treatments, Poon said he felt no substantial improvement or difference. He said he would wait three months before deciding if it had helped.

Foreigners flock to mainland

Despite the lack of a credible track record, the lure of a long-shot cure is drawing anxious Western patients to mainland hospitals for treatments costing up to HK$233,000 a month.

The stem-cell surgery of the little-known Qingdao Chengyang People's Hospital is so popular an entire floor at the top of its complex has been remade into luxurious suites for foreign patients, who fly tens of thousands of kilometres for the treatment. The hospital even hired two full-time translators and a private driver to cater to those who can't speak Chinese.

Lori Hansard, of Houston, Texas, brought her 14-year-old son with cerebral palsy to Qingdao last month after receiving two stem-cell treatments in Mexico in 2009 and 2010. His body became softer and more elastic, and he was able to sleep and eat better, after those treatments, she said. She was hoping for even better results on the mainland, as other parents had told her that the country had leapt ahead in stem-cell therapies.

"China has a big reputation in stem-cell treatment and is the place to be because you can actually see the improvement," she said. "It takes a decade for the FDA [US Food and Drug Administration] to approve something and the Americans can't wait."

With stem cells directly implanted into the boy's brain, Hansard hopes the boy will finally learn how to make normal movements and reactions.

What Hansard and Poon didn't know is that manufacturing one MSC injection can cost as little as 300 yuan (HK$359). And these cells could never cure Poon's disease.

In theory, only neural stem cells from the brain that can give rise to nerve cells and two categories of non-neuronal cells are the right type of stem cells to treat Poon's ALS. But most mainland stem-cell therapy centres provide only MSCs, which are easy and cheap to produce.

Even if Poon had been given the right cells, there are still many barriers to the development of successful stem-cell therapies. Among them: getting the cells to behave in the desired way. "To treat many neurological conditions the cells we implant will need to grow into specific types of neurons, and to work they will also have to know which other neurons to make connections with and how to make these connections," the ISSCR said. "We are still learning about how to direct stem cells to become the right cell type, to grow only as much as we need them to."

Although it is now possible to reprogram adult somatic cells to act like embryonic stem cells (induced pluripotent stem cells, iPSCs), the mainland's stem-cell therapy centres aren't capable of doing it.

A family in mourning

The Singaporean doctor is lucky he didn't feel severe side effects after the six injections.

A 30-year-old man from Jinhua city in Zhejiang who tried to cure his cerebral infarction with stem cells died four days after receiving two injections from the No. 455 Hospital of PLA in Shanghai in July. The victim's elder brother, Hong Chun, said he had seen the injections' packing at the hospital.

"It was made in Shenzhen and the hospital told me that they purchased each injection for 300 yuan from the manufacturer," he said, adding that he had received anonymous calls from Guangdong threatening him not to expose the malpractice.

Yu Shuangfeng, 68, is among 21 mainland patients who have sued the military hospital for fraud. Yu said she nearly died of strong side effects, including fever, after paying 70,000 yuan for two injections last year. Her diabetes has never been cured. Instead, it worsened.

Han Zhongchao, director of National Research Centre for Stem Cell Engineering and Technology, said the mainland's military hospitals, which weren't under the administration of the Health Ministry, were the first to offer stem cell treatments. Many small hospitals eyed the lucrative business and launched their stem-cell centres after that.

"But all of these stem cell therapies are still at the research stage, and none of them has been approved by domestic health watchdog as effective treatment," Chinese Academy of Science academician Wu Zuze was quoted by Century Weekly magazine.

The therapies may be unproved. But some doctors are using them with abandon. In Beijing's military hospitals, cells cultivated from aborted fetuses are being injected directly into patients' brains and spines. Similar fetal-cell treatments are given at the Naval General Hospital of PLA, the General Hospital of Chinese People's Armed Police Forces, Peking University Health Science Centre and many other public hospitals.

In two articles in the Second Military Medical University's journal, Tian Zengmin, the naval hospital's neurologist, detailed how they cultivated fetal brain cells taken from five- to 11-week-old fetuses to treat Parkinson's disease and cerebellum atrophy. The central government funds Tian's research.

A Shanghai father who paid 18,000 yuan for a treatment for his son with cerebral palsy said he believed all hospital-provided cells were taken from induced abortion. "Otherwise you never know whether the cells from spontaneous abortion are good enough to repair injuries," he said. Wernig said it made much more sense medically to use fetal brain tissue than MSCs to repair neural injuries, because the fetal brain actually contains neural stem cells. He said there were some clinical trials using fetal brain tissue, in particular in patients with Parkinson's disease.

"[But] the success rate was very limited and led to uncontrollable severe side effects," he said. "Scientists are trying to find out why the transplants did not lead to the desired effect. Once there is a better understanding of the process such a transplant could become possible.''

Professor Ronald Li, director of Hong Kong University's Stem Cell and Regenerative Medicine Consortium, said that although stem-cell therapy could fundamentally change medicine, almost all treatments being developed were still in the experimental stage or clinical trials, except bone-marrow transplants.

"Many hospitals and centres have obviously overstated their stem cell treatments, with very bold claims," Li said. "Too much hype is going to jeopardise a paradigm-shifting field. Although progress is being made at amazing speeds, we need to distinguish facts from hype. The field needs time and space to grow and mature, before stem cells can be turned into clinical and other applications - it will happen, but not right away."