eBook: Advanced Tools Transforming Neurology Research - 13

Characterization of Organoids
as a Preclinical Disease Model
for Neuroscience
Organoids are poised to alleviate the challenges in translating
therapies from discovery to the clinic
Introduction
Neurodegenerative diseases pose a significant
burden on individuals, societies, and global public
health. These progressive neurological disorders,
including incurable conditions like Alzheimer's
disease (AD) and Parkinson's disease (PD), are on
the rise and impacting an ever-growing number
of people, surpassing 130 million worldwide. With
age, their prevalence escalates sharply, a trend expected
to continue as life expectancy rises. Sadly,
research into these diseases has been hindered by
an inadequate grasp of their pathology, resulting
in a lackluster record in developing treatments and
exploring new therapeutic possibilities.
Current disease models introduce errors due to
their inherent simplicity or differing nature that
does not accurately reflect human models. As
such, many therapies that show early success using
preclinical models fail in clinical translation.1
Widely adopted in vitro models involve the use of
cell lines, engineered to display the desired aberrant
expression profile. However, cell lines lack
complex cell-cell interactions with a wide range
of cell types, extracellular matrix interactions,
and signaling molecules within the culture. Each
of these interactions can affect cellular structure,
proliferation, and differentiation. Despite its limitations,
in vitro models are widely adopted due
to their ease-of-use and scalability when evaluating
thousands of potential drug candidates.
Alternatively, in vivo models are a more realistic
replication of what might be found in human
models but lack human biomolecular features
that are crucial when testing for transduction efficacy.
Additionally, in vivo models have scalability
limitations as well as ethical concerns that prevent
their adoption when it comes to AAV capsid
selection.
Human organoids, miniature three-dimensional
structures cultivated from stem cells or tissue
samples, replicate the architecture and function
of specific organs or tissues.2
These tiny organ-like
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