What is Parkinson’s Disease?

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders of aging,
characterized by the degeneration of dopamine neurons (DA neurons) in the substantial nigra, leading
to the advent of both motor symptoms and non-motor symptoms. These DA neurons project to the
basal ganglia (the striatum), which is responsible for motor control and function.

The various disruptions in motor control include muscle rigidity, resting tremors, bradykinesia
(slowness of movement), and postural instability. Motor symptoms typically appear when 60–80% of
dopamine (DA) neurons in the substantia nigra are degenerated. The reliable identification of nonmotor
symptoms is equally important as many non-motor symptoms, including depression, cognitive
dysfuction, pain, and sleep disorders, precede the motor dysfunctions.

Current modalities of treatment and their Limitation:

Because DA neurons degenerate to cause a drop in dopamine release, current treatments for PD include
dopamine replacement drugs such as levodopa to increase dopamine levels, dopamine inhibitor
carbidopa to reduce dopamine degradation in the peripheral blood, and deep brain stimulation (DBS) to
the nucleus subthalamicus.

Even though dopamine replacement drugs and DBS are effective in improving the symptoms of the
patients, they cannot stop the disease progression. Moreover, current medications can cause the
development of dyskinesia (involuntary muscle movements), effectively “overshooting” the clinical
symptoms of PD.

How can stem cells play a part?

Parkinson’s is a good candidate for a stem cell therapy because the disease is caused by the loss of one
kind of cell – the dopamine neuron. Stem cells have regenerative capacity and can grow into different
types of cells and can also make many different support factors. Researchers are looking at two main
ways of using stem cells for treating Parkinson’s:
• As factories to churn out dopamine neurons or,
• As a source of growth factors to protect neurons

Current stem cell sources for Stem cell‐based therapy of PD:

1. Mesenchymal stem cells (MSC)
2. Neural stem cells (NSCs) and dopamine neurons from fetal brain tissue
3. Human embryonic stem cells (hESCs) – derived neural stem cells and dopamine neurons
4. Induced pluripotent stem cells (iPSCs) – reprogrammed from patients’ somatic fibroblasts or
blood cells

Future aspects and challenges for Stem cell-based therapy of PD:

The use of all cell sources derived – fetal NSCs, ESCs , iPSCs and iDA neurons – is fraught with
ethical, logistical, and safety concerns.
This is particularly evident with the use of NSCs and DA neurons from fetal brain and hESCs for
clinical use. Current method of using fetal DA neurons has major technical and practical limitations,
including the limited and ethically controversial availability of human fetal DA neurons, and the
potential immunological and virological complications of using nonhuman species as fetal cell sources.
The availability of iPSCs and iDA neurons has paved the road for autologous cell-based therapy of PD.
Scientific research is making great progress in the development and characterization of iPSC derived
cells for PD

Benefits of iPS cells are two-fold:

1. The opportunity to obtain the cells directly from a patient, thus potentially reducing the risk of
auto-immune reactions following cell therapy and,
2. The ability to model diseases in the lab in order to better understand a disease and identify
novel therapeutic approaches



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