Page 88 - 22-0424

The International Journal of the Royal Society of Thailand
Volume XI - 2019

Whole-
G-banded Chromosome PCR-Sanger Targeted gene exome Whole-
Modality genome se-
karyotype microarray sequencing panel sequencing quencing
(WES)
Variant(s) per 0–1 10–100 0–1 Depends on 70–100 k 4–5 million
person the number of
genes in the
panel(s).
Incidental Low Low- Low High High Highest
findings moderate
Diagnostic 1–5% 10–20% Depends on 30–40% 30–50% 40–60%
yield the
phenotype(s)

Precision therapy in neurology
The heterogeneous nature of several diseases requires application of
precision medicine which becomes an important approach for disease treatment

and prevention. It is driven by new diagnostics and therapeutics, achieving
the goal of improving clinical outcomes for individual patients, minimizing
unnecessary side effects and increasing preventive measures for better prognosis
and patients’ quality of life. The application of precision medicine to the treatment
of hereditary neurological disorders seems to be very promising. Some examples
of targeted therapies that have been successfully used are shown in Table 2 (Stein
and Castanotto, 2017; Cortese et al., 2019; Striano and Minassian, 2020).

Recent advancements in induced pluripotent stem cells (iPSCs), genome
editing tools, and the combined application of these two emerging technologies
are of great benefit in the field of precision medicine for human diseases.
Induced pluripotent stem cell technology when combined with advances in gene
engineering techniques such as ZFNs, TALENs and CRISPR-Cas9 provides an
opportunity to create gene-corrected cells derived from cells of patients with
genetic diseases (Hotta and Yamanaka, 2015; Ingrungruanglert et al., 2015;
Norbnop et al., 2020). Several studies have reported the successful corrections of
disease-causing mutations by nucleases in human iPSCs including α1-antitrypsin
deficiency (Choi et al., 2013), β-thalassemia (Ma et al., 2013), Niemann-Pick type 3
(Maetzel et al., 2014), Duchenne muscular dystrophy (Li et al., 2015), congenital
neutropenia (Nayak et al., 2015) and hemophilia A (Park et al., 2015). This
combined approach will undoubtedly accelerate the development of gene- and
cell-based therapies.

82 Precision Medicine in Hereditary Neurological Disorders:
From Diagnosis to Treatment

11/7/2565 BE 13:30
_22-0424(077-088)8.indd 82 11/7/2565 BE 13:30
_22-0424(077-088)8.indd 82