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Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease

Bryan Joselo Cedeño Quijije

4 C

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DEFINITION

APPLICATIONS IN MEDICINE

PROS AND CONS

ISSUE APPLIED

IN ECUADOR

CONCLUSION

Implantation of patient derived midbrain dopaminergic progenitor cells, differentiated in vitro from autologous induced pluripotent stem cells (iPSCs), in a patient with idiopathic Parkinson’s disease. The patient-specific progenitor cells were produced under Good Manufacturing Practice conditions and characterized as having the phenotypic properties of substantia nigra pars compacta neurons; testing in a humanized mouse model (involving peripheral-blood mononuclear cells) indicated an absence of immunogenicity to these cells. The cells were implanted into the putamen (left hemisphere followed by right hemisphere, 6 months apart) of a patient with Parkinson’s disease, without the need for immunosuppression. Positron emission tomography with the use of fluorine-18-L-dihydroxyphenylalanine suggested graft survival. Clinical measures of symptoms of Parkinson’s disease after surgery stabilized or improved at 18 to 24 months after implantation.

In Ecuador there is not the treatment about personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease, we barely use since 2013 deep brain stimulation for treatment, and it has been used with 18 patients.

The improvements in motor assessments and patient rated symptom scales in our patient should be interpreted with caution, because both he and the raters were aware of the intervention and there were no control comparisons. Clinical changes appeared gradually during the 18 to 24 months after implantation, a time frame consistent with gradual reinnervation of the putamen by projections from dopaminergic neurons. During this time, the levodopa equivalent daily dose decreased by 6%, a reduction of uncertain clinical importance.

It is uncertain whether the immune system in the central nervous system would react differently to iPSC-derived autologous as compared with allogeneic mDAPs. One goal of autologous cell therapy is to avoid the requirement for an indeterminate period of immunosuppression inherent in the use of nonautologous tissue. No immunosuppression was used in the course of this patient’s treatment, given the hypothesis that the autologous source of the original fibroblasts would yield an implantable cell product recognized as self. The graft-survival experiments in autologous as compared with allogeneic humanized mice reported here support this hypothesis. An autologous cell approach is costlier and more labor intensive than the use of generally available, precharacterized allogeneic cell lines, requiring production and safety testing for each use.

We report the production and implantation of iPSC-derived autologous dopaminergic progenitor cells in a patient with Parkinson’s disease, with clinical and imaging results suggesting possible benefit over a period 24 months. Further studies are warranted to address how this approach will perform in a variety of patients with diverse genetic backgrounds and disease phenotypes over a period longer than 24 months.

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