Biomedical Engineering Reference
In-Depth Information
parameters for maximizing cell therapeutic strategies and restoring complex
sensorimotor functions [
62
].
1.7 Neurological Diseases
Increasing evidence suggests that neuronal and synaptic dysfunction in neurode-
generative diseases are chronic and protracted processes occurring over a long period
of time. Impaired neurotransmission and excitotoxic insults often precede the
manifestation of clinical symptoms and can culminate in widespread apoptotic cell
loss. Plausible models have been suggested that describe how chronic synaptic
dysfunction can progressively develop into severe stages of neurodegeneration
[
73
-
75
]. Patients suffering from PD show first clinical signs when more than 70 % of
the dopamine (DA) neurons in the substantia nigra are already lost. Therefore, it is
crucial to search for new diagnostic methods and detect CNS diseases in their early
stages. Disease-specific markers would offer opportunities to halt or slow down
disease progression at a preclinical stage. In fact, therapeutic interventions at critical
early time points might even be the most advantageous strategy for correcting syn-
aptic dysfunction by grafted cells capable of delivering growth factors and neuro-
protective molecules such as brain-derived neurotrophic factor (BDNF), vascular
endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF1), and glial-
derived neurotrophic factor (GDNF).
I will next discuss prototypical neurodegenerative diseases that may benefit
from cell therapies and iPS cell-based disease modeling. It is important to note that
in each of these CNS diseases different cell types, anatomical compartments, and
neurotransmitter systems are affected. Hence, future cell therapy strategies need to
be tailored and firmly established considering the patient's history and the path-
ophysiology of the targeted disease. For ongoing clinical trials using NSC-based
therapies see also in Aboody et al. [
61
].
1.7.1 Alzheimer's Disease
In 1906, the German psychiatrist and neuropathologist Alois Alzheimer described
the clinical and histopathological hallmarks of a disease that was later named after
him. Alzheimer's disease (AD) is the most common neurodegenerative disease
worldwide. According to the Alzheimer's Association more than 5 million patients
are currently diagnosed with AD in the USA alone. As a consequence, more than
$170 billion are spent annually for the health care costs of AD (
http://alz.org/
)
[
76
]. There is no cure for AD and effective treatment options are not available.
Clinically, AD is characterized by progressive impairment of cognitive function,
memory loss, and dementia. Although the precise molecular underpinnings of AD
are not conclusively understood, the disease is associated with the formation
