14 Perspectives of Aptamers for Medical Applications
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14.4.2 Non-tumor
14.4.2.1 Cardiovascular Disease
Cardiovascular disease (CVD) is a class of diseases that infringe the heart or
blood vessels, which is a leading cause of death globally. CVD includes coronary
artery diseases (CAD) such as angina, myocardial infarction (commonly known as
a heart attack), acute coronary syndrome (ACS), stroke, and thrombosis, etc. An
estimated 17.9 million people died from CVDs in 2016, representing 31% of all
global deaths. Of these deaths, 85% are due to heart attack and stroke [205]. Early
diagnosis and efficient treatment will improve the clinical outcome.
Compare with the antibody, aptamer presents an advantage in the early diagnosis
and treatment field. Fast and accurate diagnosis has become crucial to prevent and
limit CVD. It is well known that effective intervention at an early CVDstage can
prevent and attenuate its progression.
Promising aptamers-based diagnosis and treatment on CVD, including ARC1779
against VWF A1 domain, NU172 against factor IIa, and REG1 against factor IXa,
stepped into clinical trials, respectively [92, 206, 207].
ARC1779
ARC-1779 is a 40-nucleotide DNA aptamer to target human VWF A1 domain,
which can block platelet activation and aggregation, as well as thrombin generation.
In 2007 [85], Gilbert et al. performed a phase I clinical trial in 47 healthy volunteers
and confirmed that ARC1779 had an antithrombotic effect and did not cause severe
bleeding events. In 2009 [92], a phase II clinical trial in patients with aTTP was
completed, seven patients received combined therapy with intravenous ARC1779
injections and plasma exchange. This trial showed no severe adverse events such
as bleeding, even in patients with aTTP who had severe thrombocytopenia. In 2011
[208], a phase I/II trial investigated the dose range of ARC1799 in patients with
cerebral embolism and a TTP. The trial showed the dose-dependent relationship
between ARC 1799 and VWF inhabitation: the high dose of ARC1799 completely
blocked the target domain on the VWF, whereas the low dose (0.5 g/mL) did not.
Besides that ARC1779 also prevented thrombocytopenia in patients with type 2B
von Willebrand disease [209, 210] (type 2B vWD). Further phase II and III trials are
needed to determine the therapeutic potential of ARC 1779 as an anti-platelet and
antithrombotic agent.
ARC2172
TBA, known as ARC183, is a promising anticoagulant drug with a rapid onset
response of desired anticoagulation activity in a significantly high dosage. ARC
2172, also known as NU172, is a second-generation aptamer for anti-thrombin after
TBA, It is an unmodified 26-mer oligodeoxynucleotide DNA aptamer which has a
short duration of action, with a half-life of 10 min in vivo. NU172 possesses a pharmacokinetic profile similar to that of TBA but with a significantly higher potency as
an anticoagulant.
437
14.4.2 Non-tumor
14.4.2.1 Cardiovascular Disease
Cardiovascular disease (CVD) is a class of diseases that infringe the heart or
blood vessels, which is a leading cause of death globally. CVD includes coronary
artery diseases (CAD) such as angina, myocardial infarction (commonly known as
a heart attack), acute coronary syndrome (ACS), stroke, and thrombosis, etc. An
estimated 17.9 million people died from CVDs in 2016, representing 31% of all
global deaths. Of these deaths, 85% are due to heart attack and stroke [205]. Early
diagnosis and efficient treatment will improve the clinical outcome.
Compare with the antibody, aptamer presents an advantage in the early diagnosis
and treatment field. Fast and accurate diagnosis has become crucial to prevent and
limit CVD. It is well known that effective intervention at an early CVDstage can
prevent and attenuate its progression.
Promising aptamers-based diagnosis and treatment on CVD, including ARC1779
against VWF A1 domain, NU172 against factor IIa, and REG1 against factor IXa,
stepped into clinical trials, respectively [92, 206, 207].
ARC1779
ARC-1779 is a 40-nucleotide DNA aptamer to target human VWF A1 domain,
which can block platelet activation and aggregation, as well as thrombin generation.
In 2007 [85], Gilbert et al. performed a phase I clinical trial in 47 healthy volunteers
and confirmed that ARC1779 had an antithrombotic effect and did not cause severe
bleeding events. In 2009 [92], a phase II clinical trial in patients with aTTP was
completed, seven patients received combined therapy with intravenous ARC1779
injections and plasma exchange. This trial showed no severe adverse events such
as bleeding, even in patients with aTTP who had severe thrombocytopenia. In 2011
[208], a phase I/II trial investigated the dose range of ARC1799 in patients with
cerebral embolism and a TTP. The trial showed the dose-dependent relationship
between ARC 1799 and VWF inhabitation: the high dose of ARC1799 completely
blocked the target domain on the VWF, whereas the low dose (0.5 g/mL) did not.
Besides that ARC1779 also prevented thrombocytopenia in patients with type 2B
von Willebrand disease [209, 210] (type 2B vWD). Further phase II and III trials are
needed to determine the therapeutic potential of ARC 1779 as an anti-platelet and
antithrombotic agent.
ARC2172
TBA, known as ARC183, is a promising anticoagulant drug with a rapid onset
response of desired anticoagulation activity in a significantly high dosage. ARC
2172, also known as NU172, is a second-generation aptamer for anti-thrombin after
TBA, It is an unmodified 26-mer oligodeoxynucleotide DNA aptamer which has a
short duration of action, with a half-life of 10 min in vivo. NU172 possesses a pharmacokinetic profile similar to that of TBA but with a significantly higher potency as
an anticoagulant.