The design of clinical trials for cell transplantation into the central nervous system
10.1602/neurorx.1.4.492 Cite this article as: Cesaro, P. Neurotherapeutics (2004) 1: 492. doi:10.1602/neurorx.1.4.492 Conclusions
Although initial excitement was raised in the medical and scientific communities by pilot trials using adrenal autografts (1980s) and fetal allograft (1990s), two controlled trials in PD patients demonstrated negative results, with the conclusion that today, cell therapy cannot be recommended for PD. Nevertheless, trials are still in progress for diseases like HD, stroke, MS, cord transection, epilepsy, and others. Human knowledge about the biology of stem cells and precursor cells is growing and we have more and more evidence that cell therapy could be useful in “repairing” brain lesions, not only by survival and integration of grafted neurons, but also by stimulation of resident precursors already present within the CNS.
The knowledge gathered from animal experiments is increasing, and several new directions may be taken. They can lead us to implant pure cell lines, with a reproducible amount, to get predicable clinical results, or to implant cells which are able to stimulate the intrinsic regenerative properties of the brain. The latter may not apply to diseases which directly affect all resident cells in the CNS (e.g., HD) but may be of critical importance for traumatic or vascular brain lesions. Finally, some of the trophic factors which may improve the survival of grafted cells could represent,
per se, a therapeutic alternative (e.g., GDNF, reelin). In a sense, their use means “to teach the brain to graft himself with its own cells.”
From a medical point of view, we have to transfer preclinical knowledge, ensuring a maximal security for the patients. This, as an ethical research, has to implement logical, comprehensive, highly controlled methods that need a complex organization. The transplantation teams should work as quickly as possible in the design of the trials, but must comply with, and not precede, the preclinical research.
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