The Story of ChinaSCINet and SCINetUSA
In 1998, Sang Lan, a young Chinese gymnast broke her neck in the Good Will Games in New York City. Her parents flew from China and, even before they went to the hospital, they came to Rutgers and asked the questions all parents ask: “Is there hope? Will there be a cure?” I told them I believed there would be a cure and that we were working hard to make it happen. In 1999, before Sang Lan returned to China, we held a dinner in Chinatown for her. At the dinner she cried. I asked why. She replied, “If you discover the cure in America, how will it come to China?” I told her that doing clinical trials in China was the only way and promised her I would do my best to make it so.
In 1999, I went to China where I gave a series of lectures for Pfizer to encourage Chinese doctors to use the drug methylprednisolone for spinal cord injury. In 1990, my colleagues and I had shown that this drug improves neurological recovery when given within eight hours after injury. In 1999, China was still a nation of bicycles that swarmed every intersection while cars inched along. Spinal cord injury was relatively rare, about 6.5 cases per million compared to 35 cases per million in the U.S. Due to limited emergency services and post-injury care, many people died.
For the next four years I went to China several times a year, giving lectures to doctors who treated spinal cord injuries, telling them of promising therapies that restore function in animals, and exhorting them to do clinical trials. In 2003, the mother of a spinal injured teenager from Hong Kong offered to pay to cure her son. Dr. Young asked her to help him establish a spinal cord injury clinical trial network in China. She introduced him to Paul Tam, pro-vice-chancellor of Hong Kong University Medical School, and Vice-Minister of Health Huang Jifu in Beijing. Professor Tam offered the support of Hong Kong University and Minister Huang gave his blessings to start a clinical trial network, urging that ethical research be done.
2004, the heads of the top spinal cord injury centers in China were invited to meet at Hong Kong University. Fifteen came to this unprecedented meeting and agreed to work together to form the first clinical trial network in China. Dr. Young took a year’s sabbatical to organize ChinaSCINet. In 2005 Dr. Wutian Wu, a professor at HKU and Dr. Young visited all the centers. Each signed research contracts to participate in joint clinical trials. In December, the first International Spinal Cord Injury Treatment and Trials Symposium was held in Hong Kong.
A fundraiser was held which included Richard Gaskin of New Jersey, known professionally as ProfessirX. The audience was riveted by his “Forever Superman” a moving tribute to Christopher Reeve who tragically had just died. Sang Lan sang a lovely Chinese folk song. It was unlike any other fundraiser and was the beginning of ChinaSCINet.
From 2006 to 2007, four meetings were held each year to train the doctors in standardized neurological examinations and clinical data collection. A group of investigators was brought to the Keck Center to learn the rat spinal cord injury model, so they could conduct research. What ChinaSCINet has accomplished is already worth the investment of time, effort, and money. In two years, standardized neurological examinations of spinal cord injury were brought to China and spinal injury doctors worked together, trusted each other, and have begun to collaborate. There now are 25 centers in mainland China, Hong Kong, and Taiwan.
In 2007, the decision was made on the first therapies to be tested in ChinaSCINet. At that time, there was only one source of well-documented cells available in sufficient numbers and diversity to be HLA-matched so the cells would not be immune-rejected. That was umbilical cord blood cells. Many laboratories had reported that these cells improved recovery in animals after spinal cord injury. Colleagues at Hong Kong University discovered that lithium, a drug long used to treat manic-depression, stimulates regeneration and promotes growth and neural differentiation of neural stem cells in the spinal cord. At the Keck Center, a student team discovered that lithium stimulates umbilical cord blood cells to grow and produce neurotrophins which promote regeneration. Thus, it was decided to study umbilical cord blood mononuclear cells and lithium treatment of chronic spinal cord injury in ChinaSCINet.
In 2008, a phase 1 trial of a 6-week course of lithium in twenty patients with chronic spinal cord injury was completed. Although seven patients dropped out, the drug clearly was safe and did not produce any significant adverse effects. In 2009, a phase 2 trial randomizing 40 patients with chronic spinal cord injury to a 6-week course of lithium or placebo was completed. Only 2 (5%) of the patients did not complete the study.
(This trial showed an unexpected result: Lithium markedly reduced neuropathic pain. Spinal cord injury not only causes paralysis and sensory loss but also causes spasticity, increased excitability of the body below the injury site, and neuropathic pain, hypersensitivity to minor stimuli and spontaneous pain. Lithium not only reduced neuropathic pain during the time the drug was given but the pain remained less for six months.)
A phase 2 trial is now underway in Hong Kong to assess escalating doses of umbilical cord blood mononuclear cell transplants in 20 patients with chronic spinal cord injury. Four, eight, and then sixteen µliters of 1.6, 3.2, and 6.4 million mononuclear cells are being injected into the spinal cord above and below the injury site, using a new imaging method called diffusion tensor imaging (DTI) to find the injury margins. Animal studies suggest that cells injected into the middle of injury site, just form an isolated island. However, cells injured at the injury margins, migrate into, and form a bridge across the injury site.
Word quickly spread in the United States that these trials were being done in China. At a Fall 2008 meeting at Magee Rehabilitation Center in Philadelphia, two large rooms overflowed with people interested in learning about ChinaSCINet. Many asked how they could go to China. This is unacceptable. People shouldn’t have to go to China to participate in clinical trials of therapies developed in the United States? Umbilical cord blood cells and lithium aren’t controversial. The only obstacle is money.
San Lang’s innocent question about how the cure was going to get from the U.S. to China has come full circle. Now Americans were clamoring to participate in clinical trials in China. Something had to be done.
So, in 2009, a spinal cord injury clinical trial network was established in the United States. Eight centers are working with the Protocol Committee, including several of the best spinal cord injury centers in the United States. The flagship hospital is Brackenridge Hospital in Austin, Texas. Governor Rick Perry gave a warm welcome to Texas and the legislature presented a Texas flag that flew over the capitol when they passed a resolution to praise SCINetUSA.