215
or the symptoms manifest later during their neonatal life. Type II SMA manifests
later in infant life and toddlers. Some of the most common symptoms of the disease
are generalized muscular weakness, difficulty in breathing, difficulty in swallowing.
Some of them may be incapable to reach the developmental milestones as sitting
upright.
The prognosis of the disease depends on the type. Especially, in patients who
suffer from type I SMA, the disease deteriorates gradually from the neonatal period
and the leading cause of death is usually respiratory failure. It should be mentioned
that a drug called Exondys 51, was approved by the FDA on September 19, 2016,
against Duchenne muscular dystrophy, although, there were many conflicts from
scientists about its utility. Another antisense oligonucleotide is indicated for infants
who suffer from spinal muscular atrophy types 1, 2 and 3. It is called Speranza or
Nusinersen and it was approved by the FDA on December 23, 2016 and is considered as a potentially life saving drug. ENDEAR study showed that with the application of Nusinersen there was a therapeutic efficacy even after the first seven months
(Traykovska et al. 2018). Although, there is a need for a longer follow up to draw
more conclusions. There is a belief that in the future antisense oligonucleotides use
will have promising effects in the treatment of neurological diseases. Defitelio or
Defibrotide is an oligonucleotide drug that was approved on April 1, 2016 and used
in cases where after application of high dose chemotherapy or after an autologous
stem cell transplantation there is severe hepatic veno-occlusive disease (sVOD)
(Rinaldi and Wood 2018; Geary 2009; Stein and Castanotto 2017; Kolb and Kissel
2011, 2015; Pane et al. 2018; Yiu and Kornberg 2015; Tsoumpra et al. 2019).
To find novel strategies for the therapy of atherosclerosis by lowering triglyceride levels, a second generation antisense oligonucleotide, Volanesorsen was developed. Its mechanism of action aims in the reduction of apolipoprotein C-III (Apo
C-III) messenger RNA. Single nucleotide polymorphisms (SNPs) in the Apo C-II
gene is related to severely elevated triglycerides. After the implementation of some
studies as APPROACH and COMPASS, the drug was approved in May 2019 for the
treatment of familial chylomicronemia syndrome (FCS) in adults. Some other studies are on a process to identify Volanesorsen’s utility in other conditions as hypertriglyceridemia, familial partial lipodystrophy (FPL) and partial lipodystrophy (Reiner
2018; Paik and Duggan 2019; Stein and Castanotto 2017).
Nowadays, antisense oligonucleotides technologies are applied in different
organisms and they seem to be very promising and popular for the treatment of
bacterial infections. The idea of their use against bacteria is based on the presence
of some proteins in bacteria, which are essential for their survival and cannot be
found in humans. Therefore, the use of antisense oligonucleotides, which target the
expression of proteins at an mRNA level, is a promising strategy for the development of novel antibiotics. More research is needed to be done in this field, due to the
urgent need for the discovery of new antibacterial drugs that will be able to fight
against the growing threat of antimicrobial resistant pathogenic bacteria (Rinaldi
and Wood 2018; Penchovsky and Traykovska 2015). The use of antisense oligonucleotides is not limited only to the protein target identification and validation.
Antisense oligonucleotides can also be used for the treatment of diseases in which
9 Drug Discovery for Targeting Drug Resistant Bacteria
or the symptoms manifest later during their neonatal life. Type II SMA manifests
later in infant life and toddlers. Some of the most common symptoms of the disease
are generalized muscular weakness, difficulty in breathing, difficulty in swallowing.
Some of them may be incapable to reach the developmental milestones as sitting
upright.
The prognosis of the disease depends on the type. Especially, in patients who
suffer from type I SMA, the disease deteriorates gradually from the neonatal period
and the leading cause of death is usually respiratory failure. It should be mentioned
that a drug called Exondys 51, was approved by the FDA on September 19, 2016,
against Duchenne muscular dystrophy, although, there were many conflicts from
scientists about its utility. Another antisense oligonucleotide is indicated for infants
who suffer from spinal muscular atrophy types 1, 2 and 3. It is called Speranza or
Nusinersen and it was approved by the FDA on December 23, 2016 and is considered as a potentially life saving drug. ENDEAR study showed that with the application of Nusinersen there was a therapeutic efficacy even after the first seven months
(Traykovska et al. 2018). Although, there is a need for a longer follow up to draw
more conclusions. There is a belief that in the future antisense oligonucleotides use
will have promising effects in the treatment of neurological diseases. Defitelio or
Defibrotide is an oligonucleotide drug that was approved on April 1, 2016 and used
in cases where after application of high dose chemotherapy or after an autologous
stem cell transplantation there is severe hepatic veno-occlusive disease (sVOD)
(Rinaldi and Wood 2018; Geary 2009; Stein and Castanotto 2017; Kolb and Kissel
2011, 2015; Pane et al. 2018; Yiu and Kornberg 2015; Tsoumpra et al. 2019).
To find novel strategies for the therapy of atherosclerosis by lowering triglyceride levels, a second generation antisense oligonucleotide, Volanesorsen was developed. Its mechanism of action aims in the reduction of apolipoprotein C-III (Apo
C-III) messenger RNA. Single nucleotide polymorphisms (SNPs) in the Apo C-II
gene is related to severely elevated triglycerides. After the implementation of some
studies as APPROACH and COMPASS, the drug was approved in May 2019 for the
treatment of familial chylomicronemia syndrome (FCS) in adults. Some other studies are on a process to identify Volanesorsen’s utility in other conditions as hypertriglyceridemia, familial partial lipodystrophy (FPL) and partial lipodystrophy (Reiner
2018; Paik and Duggan 2019; Stein and Castanotto 2017).
Nowadays, antisense oligonucleotides technologies are applied in different
organisms and they seem to be very promising and popular for the treatment of
bacterial infections. The idea of their use against bacteria is based on the presence
of some proteins in bacteria, which are essential for their survival and cannot be
found in humans. Therefore, the use of antisense oligonucleotides, which target the
expression of proteins at an mRNA level, is a promising strategy for the development of novel antibiotics. More research is needed to be done in this field, due to the
urgent need for the discovery of new antibacterial drugs that will be able to fight
against the growing threat of antimicrobial resistant pathogenic bacteria (Rinaldi
and Wood 2018; Penchovsky and Traykovska 2015). The use of antisense oligonucleotides is not limited only to the protein target identification and validation.
Antisense oligonucleotides can also be used for the treatment of diseases in which
9 Drug Discovery for Targeting Drug Resistant Bacteria