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

Example of important diseases

In this article, only breakthrough and marketed treatment will be discussed.

1. Spinal muscular atrophy
This disease is caused by nonsense or frame shift mutation in survival
motor neuron 1 gene. This gene is coded for protein responsible for motor neuron
survival. Clinical manifestation depends on the severity of the mutation and the
amount of remaining protein. In severe cases, the patients will present as floppy
baby syndrome, respiratory failure and they will survive for a few months. In less
severe cases, the symptoms may start in adolescent and they may survive throughout
adulthood with chronic weakness or long term disability.

Based on the genetic knowledge, there has been continuous research finding
the specific treatment for this disease, especially in pediatric group. The most effective
way is to administer the medication or agent to modify genetic transcription and
finally increase the deficient protein (Levin AA, 2019).

In early studies, nusinersen, one of the oligonucleotide therapies was
administered intrathecally in the young infant (mean age 2 months). It is very
effective in prolonging life, reducing ventilator dependence and improving
muscle power (Fingel RS, et al, 2017). A subsequent study in older infants and
toddlers also showed similar results (Mercuri E, et al, 2018). Finally, US-FDA had
approved this drug to use in genetically confirmed patients. However, the cost is
very high, around 750,000 US dollars in the first year and 375,000 US dollars per

year for the rest of their life. This issue had been widely criticized in the public
regarding its pricing, cost effectiveness and accessibility (Thomas K, et al, 2016).
Gene replacement therapy is the next frontier in this disease. The patient
will be intrathecally injected the adenovirus virus carrying the SMN gene for one
time. The treatment group has clear better outcome when compared to the control
group (Mendell JR, et al, 2017. Although the number of patients is still limited, but

it is a novel therapy in the untreatable disease. In May 2019, US FDA approved
this gene therapy (Onasemogene abeparvovec–xioi) in patients who are less than
2 years old. Nevertheless, the cost of treatment is approximately two million dollars
per treatment (Brooks M, et al, 2019). Therefore, this precision therapy is the triumph
for untreatable genetic disease. Using genetic information is critical for diagnosis
and treatment. Genetically specific therapy will be the next step forward in this
deadly disease. The cost involved is still the huge hurdle for its accessibility.

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Kongkiat Kulkantrakorn

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