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Autologous Dopaminergic Progenitor Transplantation Alleviated Parkinson's Symptoms

Review of "Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys" from Nature Medicine by Stuart P. Atkinson

The feasibility of transplanting dopaminergic progenitors/neurons derived from autologous induced pluripotent stem cells as a treatment for Parkinson's disease has been demonstrated in both non-human primates [1, 2] and a single human patient [3]. Unfortunately, effectiveness remains unproven as these studies revealed only minor improvements/disease recovery [2, 3].

A new study from researchers led by Marina E. Emborg and Su-Chun Zhang (University of Wisconsin–Madison, Madison, WI, USA) sought to definitively evaluate the effectiveness of autologous transplantation therapy, and now Tao et al. report that Parkinson's monkeys receiving autologous dopaminergic progenitor transplants displayed improvements to both motor and depressive symptoms [4].

The authors employed older monkeys and transplanted dopaminergic progenitor cells three years after inducing Parkinson's disease by injecting the neurotoxin MPTP in the unilateral right intracarotid artery [5] to mimic future clinical applications. Encouragingly, the study reported that Parkinson's disease monkeys receiving autologous transplants of rhesus induced pluripotent stem cell-derived dopaminergic progenitors [6, 7] displayed signs of recovery from motor deficits and, unexpectedly, also from depressive behaviors in a two year period after transplantation in the absence of any immunosuppression.

Interestingly, the study linked these significant improvements to the robust grafting of autologous dopaminergic progenitors into host tissues and the subsequent extensive dopaminergic neuron axon growth and robust dopaminergic neuron activity, with the latter evidenced by positron emission tomography. The authors also reported the application of mathematical modeling to correlate the number of surviving dopaminergic neurons with positron emission tomography signal intensity and behavioral recovery following autologous dopaminergic progenitor transplant.

Overall, the authors report the safety and efficacy of autologous dopaminergic progenitor transplantation in a non-human primate model of Parkinson's disease. While autologous therapy does not require immunosuppression, the authors note the requirement for more protracted and expensive protocols; however, ongoing technological innovations regarding induced pluripotent stem cell generation and dopaminergic differentiation may make autologous approaches more feasible for human patients in the future.

For more on the development of autologous stem cell therapy as an effective treatment for Parkinson's disease, stay tuned to the Stem Cells Portal!

References

  1. Emborg Marina E, Liu Y, Xi J, et al., Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain. Cell Reports 2013;3:646-650.
  2. Hallett Penelope J, Deleidi M, Astradsson A, et al., Successful Function of Autologous iPSC-Derived Dopamine Neurons following Transplantation in a Non-Human Primate Model of Parkinson's Disease. Cell Stem Cell 2015;16:269-274.
  3. Schweitzer JS, Song B, Herrington TM, et al., Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease. New England Journal of Medicine 2020;382:1926-1932.
  4. Tao Y, Vermilyea SC, Zammit M, et al., Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys. Nature Medicine 2021.
  5. Emborg-Knott ME and Domino EF, MPTP-Induced Hemiparkinsonism in Nonhuman Primates 6–8 Years after a Single Unilateral Intracarotid Dose. Experimental Neurology 1998;152:214-220.
  6. Fusaki N, Ban H, Nishiyama A, et al., Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proceedings of the Japan Academy, Series B 2009;85:348-362.
  7. Xi J, Liu Y, Liu H, et al., Specification of Midbrain Dopamine Neurons from Primate Pluripotent Stem Cells. STEM CELLS 2012;30:1655-1663.