Despite many niggling concerns still holding back stem cell therapies, Japan has just approved a stem cell treatment for spinal cord injury. However, according to experts approached for comment by Nature ― ten specialists in stem-cell science or spinal-cord injuries that were not involved in the work ― evidence that the treatment works are insufficient. Furthermore, they suggest that the clinical trial on which the approval was based was too small and poorly designed.
The Japanese stem cell therapy, called Stemirac, involves isolating a patient’s own mesenchymal stem cells ― a type of ‘adult’ stem cells ― from their bone marrow, expanding them to larger numbers in the lab, and intravenously infusing the cells back into the patient within 40 days of a spinal cord injury. The expanded stem cells are expected to restore damaged nerve cells and improve paralysis by reducing inflammation and protecting existing neurons. The researchers involved in developing Stemirac even suggest some stem cells may actually develop into neurons to replace those lost as a result of the injury. However, independent scientists argue that although MSCs may be able to take on certain features, they have not been shown function as neurons.
The safety of various types of autologous stem cell infusions ― derived from a patient’s own cells ― has not been fully established. Previously trials of stem cell therapies have reported dangerous blood clots and lesions (1). Moreover, stem cells often become trapped in the lungs where they cannot provide any therapeutic benefits.
The health ministry panel gave the conditional green light to the company in November last year, to commercialise the stem cell therapy jointly developed with Prof Osamu Honmo from Sapporo Medical University. As of 24 January, the company is now allowed to market and sell the therapy provided they collect data from participants over the next seven years to demonstrate its effectiveness.
The recent approval deviates from established approval procedures put in place to ensure the safety of patients by carrying out valid clinical trials. Many other countries require rigorous clinical testing with hundreds of patients before new therapies can be sold. Japan has put a programme in place to fast track regenerative medicine therapies within minimal evidence of efficacy, based on the condition that follow-up data is collected.
The approval of Stemirac was based on the results of an unpublished clinical trial involving only 13 patients with spinal cord injuries. According to the results, 12 out of 13 patients improved by at least one level on the American Spinal Injury Association impairment scale after six months. In other words, the patients regained some degree of sensation and movement. However, the trial was not double-blinded ― the gold standard for assessing new treatments ― which makes it difficult to determine the long-term efficacy of the treatment. Without double blinding, it remains unknown whether patients would have recovered naturally.
Masanori Fukushima, a Japanese oncologist involved in the work, argues that the results are “unprecedented” and most of the patients were too seriously injured to recover naturally.
(1) Thirabanjasak, D., Tantiwongse, K., and Thorner, P.S. Angiomyeloproliferative Lesions Following Autologous Stem Cell Therapy. Journal of the American Society of Nephrology (2010) DOI: 10.1681/ASN.2009111156