Reprogrammmed Stem Cell Clinical Trial for Brain Cancer

Researchers from the City of Hope Beckman Research Institute in Duarte, California have been given permision by the FDA to carry out a small-scale clinical trial to inject reprogrammed neural stem cells into the brains of terminally ill patients suffering from recurrent glioma.


Only 20 patients will be treated, and the trial is to assess the potential safety of the procedure before authorisation for larger scale trials of efficacy of the treastment can begin.


The patients to be treated will only have 3 to 6 months to live, and will have to have had tumour resection surgery to remove the majority of the cancer. The cells will be injected locally a the site of re-section and is aimed at targetting the remaining cancer cells individually.


The neural stem cells have been genetically modified to secrete the enzyme cytosine deaminase whose target will be 5-fluorocytosine, which will be administered systemically on a daily basis. Deamination of the cytosine will produce the well known, but toxic, anti-cancer drug 5-fluorouracil.


The team believe that local conversion at the site of disease will result in maximising the concentration of the active drug whilst leading to much smaller systemic side effects. Previous trials in mice lead to significant reduction in brain tumours in the diseased animals compared to those which had been untreated.


Many have criticised trials of stem cell therapies to repair brain degeneration due to the inherent risk of cancer from the uncontrolled proliferation of the injected cells. However, the neural stem cells used in this trial have not been observed dividing following 48 hours after their delivery into the brain.


If the trial is successful, and there is evidence that the recurrence of glioma has been halted, or severely postponed, it will bring credence to the hypothesis that stem cells and cancer cells migrate using the same, or similar biological cues. Furthermore, it is likely that new treatments for non-neural carcinomas will be designed based on the same principle.


Nick Rhodes

Gene therapy has been used to restrore sight

For the first time in humans, gene therapy has been used to restrore sight. The study, at the University of Pennsylvania, was designed to test the safety of the procedure, but the results were much better than anticipated.


The treatment was applied to two patients suffering from Leber’s Congenital Amaurosis (LGA), a rare congenital condition in which the patient’s have severely reduced vision due to the lack of the RPE65 gene, a retinal pigament epithelium specific protein, which is required for the maintenance of the epithelial cells covering photoreceptor cells in the retina.


Estimates showed that light levels after 90 days were increased by a factor of almost 5 orders of magnitude compared to the pre-treated state.


However, this is a treatment for just one type of LGA, which is merely one of many forms of blindness, the causes of which are often much more comlicated in terms of their etiology compared with the current study. Nevertheless, this study demonstrates the applicability of gene therapy as a paradigm to the treatment of both congenital and degenerative forms of blindness.


Nick Rhodes