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

2. Hereditary transthyretin amyloidosis
This disease is inherited by autosomal gene which carries mutated
transthyretin gene (TTR). The pathology shows amyloid accumulation in bodies

such as nerve, heart kidney, gastrointestinal tract which cause organ dysfunction.
In case of cardiac involvement, the survival is around 2-5 years. There had been
no specific treatment except liver transplantation. Recently, the breakthrough
has arrived. If specific mutation is found, RNA interference (RNAi) therapy can be
given to reduce the accumulation of amyloid. Patisiran, one of RNAi, given
intravenously every 3 weeks can reduce blood transthyretin level, improve motor
function, less neuropathy severity and increase quality of life (Adams D, et al,
2018). Inotersen is another agent which has similar mechanism, also shows
impressive result (Benson MD, et al, 2018). Based on the studies, both US FDA
and European Medicines Agency (EMEA) have approved marketing authorization
of these drugs in 2018.

3. Duchene muscular dystrophy
Duchene muscular dystrophy is a severe inherited myopathy which is
found in 3,600 to 6,000 male newborns. It is caused by mutation in dystrophin
gene at locus xp 21.2. This gene is directly responsible for dystrophin protein
which is the largest muscle membrane protein. Lacking of this protein causes
muscle membrane instability and disruption, leading to progressive muscle loss
and weakness (Birnkrant DJ, et al, 2018).

The diagnosis is often made in early childhood, around 5 years old. It is
recognized by progressive proximal muscle weakness and motor development
decline. At the end, the patients will not be able to walk prior prepuberty age. They
will succumb to death before adulthood due to complications such as scoliosis,
respiratory failure, cardiomyopathy, etc. Current care is mainly focused on
symptomatic treatment, prevention or correction of complications. Steroid has
shown marginal benefit in prolonging walking period in early phase of the disease,
but this treatment is limited by steroid related complications (Birnkrant DJ, 2018).

For the past several decades, there have been attempts in alleviating
deficient dystrophin causing by frameshift mutation of dystrophin gene. Its mRNA
was truncated and dystrophin is not produced. Exon skipping therapy is the way
to bypass the transcription of mutated gene at exon 51 location and it hopes to
continue transcribing this mRNA. Even though this new mRNA is shorter, but
newly translated dystrophin is at least partially functional.

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