Stem Cell Treatments for Parkinson’s Disease

The treatment is based in the ability to direct the fate of these cells to become dopaminergic neurons. The most promising stem cell types are embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSC). Human ESCs are harvested from the inner cell mass of the early blastocyst, and a number of human ESC cell lines have been generated from excess embryos from in vitro fertilization procedures. On the other hand, iPSCs are generated by the reprogramming of an adult somatic cell (such as a dermal fibroblast) into a stem cell, through the expression of a number of transcription factors that could induce pluripotency (c-myc, klf-4, sox2, and oct4). The main method of administration is via injection of the SC in the brain regions related to dopamine secretion (1, 2).

Short and Mid Term Results

Long – Term Results

In late 2017, researchers in Jun Takahashi, MD, PhD’s lab at the Center for iPS Cell Research and Application at Kyoto University in Japan announced that a study transplanting nerve cells made from iPS cells into the brains of pre-clinical models was promising. The grafted cells were able to secrete dopamine and stimulate neurons in the brain. The implanted cells survived for two years (2019), appeared to improve symptoms and did not cause ill side effects.

In July 2018, the Kyoto researchers announced plans to start a clinical trial moving the procedure into humans. Researchers inject dopaminergic progenitor cells — cells that develop into neurons that produce dopamine — directly into an area of the brain associated with neural degeneration in Parkinson’s disease. The scientists completed the first transplant in October and plan to complete six additional operations by 2022.

References

1. Stoker TB. Stem Cell Treatments for Parkinson’s Disease. In: Stoker TB, Greenland JC, editors. Parkinson’s Disease: Pathogenesis and Clinical Aspects [Internet]. Brisbane (AU): Codon Publications; 2018 Dec 21. Chapter 9. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536728/ doi:  10.15586/codonpublications.parkinsonsdisease.2018.ch9   
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2. Stem Cells for Parkinson’s: Therapy and Tools for a Neurological Disorder – A Closer Look at Stem Cells [Internet]. Closerlookatstemcells.org. 2019 [cited 30 December 2019]. Available from: 
https://www.closerlookatstemcells.org/2019/04/01/stem-cells-for-parkinsons-therapy-and-tools-for-a-neurological-disorder/ 
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Ejemplo de transgénico animal en Parkinson´s

For practical reasons, small size and low cost of housing, their short generation time, and their fairly well defined genetics, mice are the best tools to study the pathogenesis of PD. LRRK2 KO mice are viable and have an intact nigrostriatal DA pathway up to 2 years of age. These transgenic materials were applied by intrastriatal injection in all the experiments. Neuropathological features associated with neurodegeneration or altered neuronal structure were absent, but α-syn or ubiquitin accumulation has been reported in these mice. To date, two LRRK2 KO rat models have been developed, although the consequences of LRRK2 deficiency in the brain are still unknown (1).

Advantages of Transgenic Animals:

(a) Gene requires certain cellular mechanism to help for the production of protein. The animals used for transgenic purpose natu­rally carry the mechanism needed to pro­duce complex protein. Theses mechanism is absent in cell culture.

(b) Expression through cell culture or bacte­rial culture requires constant monitoring and sampling.

(c) The isolation and purification of expressed protein in conventional method is more difficult than purifying proteins from an animal’s milk or body fluid.

(d) It is more cost effective as the product is efficiently passed through milk with an average yield of 53% and with 99% purity.

(e) It has been estimated that transgenic ani­mal can produce in its lifetime $100 to $200 million worth of pharmaceuticals.

Disadvantages of Transgenic Animals:

(a) Transgenic animal project is extremely expensive.

(b) Generation of transgenic animals are also expensive, because of long gestation pe­riod, litter size and higher maintenance cost of the recipient animals.

(c) There may be high mortality rate and other deleterious effects on animals used by researchers to create transgenic breeds. It has been observed that transgenic pigs having enhanced growth rate and efficient feed conversion exhibit reduced reproduc­tive performance and may suffer from ar­thritis and dermatitis etc. Similarly, transgenic sheep expressing growth horm6ne may show diabetic like condi­tions. Mayer argues that we do not under­stand the long term effects of genetic engineering on animals.

(d) Large number of recipients is required for embryo transfer because of low transgene­sis rate.
(e) Transgenic foods have been produced and offer better productivity in terms of both yield and quantity. However, there are some apprehension about the safety of transgenic foods.

Reference

1. Blesa J, Przedborski S. Parkinson´s disease: animal models and dopaminergic cell vulnerability. Frontiers in Neuroanatomy. 2014;8.

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