Therapeutic Potential of Stem Cells in Neurodegenerative Diseases

59

oration and inducing motor neuron survival [140]. Following to Ropinirole, it

underwent a phase I trial in 2019 [141]. Tauroursodeoxycholic acid (TUDCA),

a hydrophilic bile acid, was also reported to prevent the degeneration of motor

neurons derived from mouse and human ESC lines carrying SOD1 mutations.

TUDCA also promoted neurite outgrowth in vitro and lessened muscle den-

ervation in a mouse model [142]. These neuroprotective findings led to dis-

tinct clinical trials in phases II and III (NCT00877604, NCT03127514, and

NCT03800524). Lastly, screening with 160 bioactive small molecules in hu-

man ESC- and iPSC-derived motor neurons yielded the Rho kinase inhibitor

Y-27632 as an anti-ALS medication. As shown, administration of Y-27632,

or Fasudil, induced neural proliferation, amplified neuron number, and en-

hanced response to neurotrophic factors compared to vehicle control [143].

Subsequently, Fasudil has also been subjected to a phase II clinical trial re-

cently (NCT03792490).

It is obvious that each clinical trial has been initiated as a consequence

of drug testing using pluripotent stem cell-based platforms. So, the success

of repurposed drugs in clinical trials has also authenticated the reliability,

adaptability, and truth of pluripotent stem cells in ALS research, from the

laboratory to the clinic.

2.3.4.2

NSCs and MSCs in ALS Precision Cell Therapies

Numerous preclinical investigations have been deducing the victory of transla-

tional stem cell therapy for ALS [144, 145]. In 2012, pioneering clinical research

published that autologous transplantation of CD133-positive NSCs within the

frontal motor cortex of 67 ALS patients was deemed safe and well-tolerated

with mild adverse effects [146]. Another phase I study conducted on a cohort

of six sporadic ALS patients illustrated that surgical implantation of fetal

NSCs into the anterior of the spinal cord halted disease progression with no

severe side effects [147]. Similarly, MSC administration in participants within

the scope of phase 1/2 (NCT01051882) and 2a (NCT01777646) clinical trials

resulted in an upturn in ALS-related scores and in muscle atrophy progres-

sion owing to neurotrophic factors secreted by transplanted MSCs [148]. Since

drawbacks and limitations of current stem cell therapies for ALS treatment

exist, developing safer and more convenient methods is indispensable.

2.4

Conclusion

Even though there is a great variety of neurodegenerative diseases in humans,

loss and/or dysfunction of certain neuron types in the nervous system under-

lie the basis of all. Replacement of the lost or faulty neurons with properly

functioning cells appears as the most plausible, efficient, and well-tolerated

treatment strategy. In this sense, various stem cell types have been shown to