Gene therapy patient monitoring

It is obvious that angiogenic therapy for ischemic heart disease using gene therapy, cell transplantation, and hematogenous cytokine administration will benefit increasing numbers of patients. However, long-term studies monitoring side effects to... 

Thus, they established procedures for clinical trials and other experimentation with humans in which researchers are expected to follow a precautionary protocol for selecting patients and applying experimental methods and products to them, monitoring their response, and then do full and timely reporting of any adverse outcomes to enable open discussion and evaluation of the causes, quick determination of corrective actions needed for patient safety, and rapid dissemination and implementation of the corrective actions in all related research projects. It now appears that this model for safeguarding human subjects needs reinforcement for it to be sufficient in the competitive and economically opportunistic culture in which gene therapies are tested. 

Fig. 13.2 Thiopurine methyl transferase (TPMT) methylator genotypes in Crohn s disease during azathioprine/6-mercaptopurine (AZA/6-MP) treatment influences the time in months to development of severe myelosuppression. However, only 27% of patients with Crohn s disease and myelo-suppression during AZA therapy had mutant alleles of the TPMT gene associated with enzyme deficiency. Myelosuppression is more often caused by other factors. Continued monitoring of blood cell counts remains mandatory in patients treated with AZA. (Reproduced from ref 35.)...

Of the toxic side effects, a major concern among clinicians is for dose-dependent bone marrow suppression (myelotoxicity), which occurs in 2. 6% of patients and can be fatal if not addressed properly. Study data suggest that a high incidence of secondary acute myeloid leukemia or brain cancer is correlated with low TPMT activity and high 6-TGN levels in children under immunosuppressive therapy. TPMT activity is subject to wide interindividual and interethnic variability due to TPMT gene polymorphism. In the Caucasian population, 0.3% of all individuals have no TPMT activity and 11% have intermediate activity, leading some to advocate additional monitoring of this activity in patients to help prevent unnecessary bone marrow toxicity from azathioprine treatment. 

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