Approaches to Personalised Medicine Based on Genetic and Metabolic Profiling

COURSEWORK PART 2

Question 1
Describe Pharma industry approaches to the treatment of cerebral ischemic brain damage
following a stroke. Your answer should describe the known drug targets based on the
current understanding of the mechanisms of cerebral ischemic damage and neuronal cell
death as well as approaches to restoring blood flow and stroke prevention.
Cerebral ischaemic brain damage can be defined as a condition when there isn’t sufficient blood
flow to the brain in order to meet metabolic demand. This situation is responsible for limited
oxygen supply or cerebral hypoxia which leads to death of brain tissue, cerebral infarction or
ischaemic stroke. However, it can be consider as sub-type of stroke along with subarachnoid
haemorrhage and intra cerebral haemorrhage (Feng and et. al., 2017). This health problem
indicates number of symptoms such as impairments in vision, body movement & speaking,
unconsciousness, blindness, problems with coordination and weakness in the human body. There
are various kinds of pharma approaches that are used by medical practitioners in order to solve
the problem of cerebral ischaemic brain damage. It involves several categories of medications
such as thrombolytics and other antiaggregation compounds along with neuroprotective agents.
Figure 1: Acute Ischaemic Stroke Therapy
(Source: Acute Ischaemic Stroke Therapy, 2017)
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Mechanism of pharmaceutical approach of thrombolytics
Most of the countries give license to thrombolytics in terms of clinical use regarding
acute ischaemic stroke is rt-PA (alteplase) which was previously used for myocardial infarction.
This medication has a chemical mechanism which increases the incidence of cerebral
haemorrhage that is a health issue which can be mimicked in experimental organisms. This drug
has a role to boosting up the levels of matrix metalloproteinase-9 in the endothelium. In the other
hand the other thrombolytic is known as desmoteplase which is required for fibrin as a cofactor
as it has more potential as compared to rt-PA in presence of fibrin (Zhao and et. al., 2016).
However, it has been analysed that desmoteplase is much effective as well as efficient in respect
of having capability to dissolve clots without increasing systemic clotting and thereby enhancing
haemorrhagic transformation which occurs due to intake of rt-PA. It is observed that rt-PA has a
side effect whereas desmoteplase is appropriate for clinical use to support patient to overcome
with problem of cerebral ischaemic brain damage. Meanwhile, it has been evaluated that few of
preclinical evidence recommend that rt-PA may leads to extracellular space in CNS and it can
induce neurotoxicity which is not observed in case of using desmoteplase.
Antiaggregation compounds and other perfusion-enhancing compounds
This involves the monoclonal antibody abciximab which is an antiaggregation
compound that binds to glycoprotein IIb/IIIa receptor on the platelets surface. It is responsible
for promoting the fibrinolysis via prevention of from sticking together, thereby inhibiting clot
formation. Meanwhile, it has been analysed that this medication is currently used for restoration
of coronary blood flow and it often being given with combination of thrombolytic. In addition to
this, it is observed that heparin intake within 3 hours is beneficial for patients with cerebral
ischaemic brain damage but it also create problem of cerebral haemorrhage then it is not suitable
(Kowoll and et. al., 2016). However, another pharma compound like plasmin and micro
plasmin that are free of having side effect of cerebral haemorrhage then it is suitable for patients
suffering from cerebral ischaemic brain damage to help them to overcome with the disease. It
can be consider as an effective option for people to intake this medication with appropriate
dosage which is required according to their condition of cerebral ischemia to become disease
free. It is necessary for care professionals to evaluate performance of different pharmaceutical
compounds as per actual need of patient to provide accurate dose of medication. It is favourable
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