I decided to set up a thread of posts about ChinaSCINet. I apologize in advance for the disorganized fashion of this topic. If I stop to write this in a formal way, it takes time and sometimes doesn't get posted until several days later. So, I am writing this off the cuff without a lot of editing and hoping that it makes sense.
I just returned from China and Hong Kong. Professor Kwok-Fai So and I visited Dr. Zhu Hui at the Kunming Army General Hospital. We were very impressed by their new hospital and operating facilities. I met their patients while they were doing their calisthenics in the morning. They are working very hard and doing intradural decompression on many of the patients. The good news is that they have now received formal permission from the Military go ahead with the planned clinical trial. The Department of Science and Technology of Yunnan province is providing some support for the trial. We are applying to the Ministry of Health in Beijing and of Yunnan Province for permission to import cells from the United States to the hospital for the trial. We have been assured that this permission should be provided in the next few weeks. In the meantime, we have arranged for technicians and doctors to be trained at the Chinese University of Hong Kong to learn how to process the cells and will be carrying out validation of the cells in the coming month. It is my fervent hope that they can start the surgery before the end of 2010. Most of the major obstacles have been taken care off and here is to hoping that there are no more.
The clinical trial in Hong Kong is commencing. We applied for and have received permission from the Institutional Review Boards of both HKU and CUHK to allocate patients to the treatment groups sequentially, rather than randomly. The first surgery has been tentatively scheduled for October 11. The cells are ready to go and we have completed validation of cell viability and quality. Five patients have been qualified. Several others may soon qualify. We are hoping that more people will volunteer to be screened for the trial.
Professor So and I, as well as Professors Wai San Poon and Gilbert Leung, spoke to a group of over 100 people on Sunday (August 29, 2010) in Kowloon, at a lecture hall next to the Kowloon Hospital. for over 3 hours, we spoke and answered questions about the trial. I did not do a count but I believe that over 50 people with spinal cord injury attended. There were many questions and we tried to answer all of them as honestly as we can. Below are some of my impressions concerning the meeting.
- Professor So and I reviewed most of the published literature on the subject of umbilical cord blood cell (UCB) mononuclear cell (UCBMC) therapies and lithium therapy of spinal cord injury. We pointed out that a large body of literature has shown beneficial effects of UCBMC and lithium alone in rats. In the case of UCBMC, there are several dog studies as well. UCBMC also appear to prevent cell death and are anti-inflammatory, providing strong justification for the use of the cells in acute spinal cord injury.
- Somebody asked about efficacy of the treatment in chronic animal SCI. I pointed out that we have not been able to test the combination therapy (UCBMC + lithium) because there is no such thing as HLA-matched umbilical cord blood and cyclosporin immunosuppression is necessary to assure survival of the cells for more than 3 weeks in the spinal cord. Unfortunately, cyclosporin blocked the effects of lithium in the spinal cord. On the other hand, there is ample evidence that umbilical cord blood cells or lithium alone, when given shortly after injury improves recovery. Several studies gave the human umbilical cord blood as late as 1-2 weeks after injury and still showed significant beneficial effect.
- Dr. Leung and Dr. Poon talked about the surgery, pointing out that two small laminectomies above and below the injury are very unlikely to harm the spinal cord or to produce instability. However, it is essential that they can get good MRI images of the spinal cord to determine the best place to operate. As I have indicated here before, direct visual inspection of the spinal cord at the time of surgery is the safest way to inject cells into the spinal cord.
- We emphasized that we will be using HLA-matched umbilical cord blood cells and that the cells are transplanted into the spinal cord. I pointed out that the reason why umbilical cord blood cells may have not been particularly effective in other places such as Shenzhen, India, and other medical tourism clinics may be because they have been injecting non-matched cells intravenously or intrathecally. In my opinion, the cells must reach and get into the spinal cord to be beneficial. If one does not use HLA-matched cells, the cells will be immune-rejected rapidly by the body. To inject non-HLA matched cells intravenously or intrathecally, as they are doing in Beike Biotech and other places, is a waste of time and money.
- There was some discussion about higher cervical spinal cord injuries and lower T11-L1 (lumbosacral) injuries. Dr. Poon explained that injection of cells into the spinal cord about a C4 injury may damage the phrenic nucleus that is responsible for breathing and that risk should not be undertaken until we know more about the benefits of the treatment. I pointed out that injuries to the lower thoracolumbar cord may not benefit from cord blood cells transplants as much and that we will need neuronal replacement therapies for people with flaccid paralysis of the legs.
- There were questions from people who were older than 60. The trial in Hong Kong was approved for people 18-60. [Note: We will try to get approval of the trial in the U.S. for people from 18-64.] I said to the audience that older people have a higher risk of complications from surgery. For a first trial, we did not think that this risk is worthwhile but that we are committed to test the safety of this trial in older patients after the current trial shows that it is safe in adults from 18-64. I also said that we are planning a trial in the U.S. for children ages 8-17.
- One man asked repeatedly about whether or not I would help him to go to doctors in Shenzhen or other parts of China to get this therapy into patients (presumably him). I told him that we are not there to provide therapies to patients and our goal is to test therapies in credible clinical trials and to show the therapies work or do not work. If the clinical trials show that the therapies work, they will be widely adopted by doctors and will benefit many people. If the therapies don't work, we stop wasting time and resources on therapies that don't work and focus on the ones that do. He seemed quite angry that it has taken so long and that he has been waiting 6 years. I spoke to him later and will see him when I go to Hong Kong next to see if I can suggest what he can do for his condition.
After this "town-hall meeting", the investigators met and discussed the details of the trial. There is a lot of do in the coming weeks.