Pharmacological Treatments for Cerebral Ischemic Damage & Alzheimer's

This report provides a detailed overview of pharmacological approaches to treat cerebral ischemic brain damage and Alzheimer's disease. The first part of the report focuses on the pharma industry's strategies for cerebral ischemic damage, including thrombolytics, antiaggregation compounds, and antiplatelet therapy, detailing their mechanisms and clinical applications. The second part critically reviews the potential of disease-modifying immunological drugs in the treatment of Alzheimer's disease, based on the provided research paper and additional references. It examines the amyloid hypothesis, the role of anti-amyloid-β monoclonal antibodies, and the challenges and promise of immunotherapy, including the latest clinical trial findings and future research directions. The report emphasizes the importance of understanding disease mechanisms, drug targets, and prevention strategies to improve patient outcomes. This analysis is essential for understanding and evaluating current and future treatment options in neurology and pharmacology.

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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to overcome with problem of cerebral ischemic brain damage problem without having any kind
of side effects on human body.
Antiplatelet therapy
It has been analysed that antiplatelet drugs plays an important role in medical treatment
which is broadly used in non-steroidal anti-inflammatory drugs (NSAID) acetylsalicylic acid
which is generally known as aspirin and its many derivatives. Aspirin is used as an
inflammatory drug historically as well as in correct scenario. It get distributed aiming tissues and
inside intracellular compartment for effectively blocking of COX (cyclooxygenases) and thus the
synthesis of prostaglandis. However, in context of aspirin, it functions as a platelet anti-
aggregant that requires lower dosages to become distributed within intravascular compartment,
in fact it being independent of systemic bioavailability in the portal circulation. In addition to
this, aspirin has a mechanism to get bind and inhibits platelet COX-1 irreversibly and
consequently impairs the creation of prostaglandis as well as thromboxanes, noting thromboxane
A2 (TXA2) in particular (Bustamante and et. al., 2016). It has been analysed that the absence of
TXA2 leads to decrease in TXA2-mediated amplification of activating platelets and thus
responsible for hindering the platelet aggregation phenotype. However, the phenotype contains
morphological modifications and expression of fibrinogen receptors that is necessary in regards
to platelet aggregation respectively.
Considering the above pharmaceutical approaches with their mechanism, it has been
analysed that they work in order to solve problem of cerebral ischaemic brain damage. It
includes various types of procedures of medications in terms of dissolving clots or preventing the
formation of blood clots to make an individual disease free. However, it is necessary for care
professionals to effective analysis the actual condition cause of cerebral ischemia according to
which appropriate decision making should be carried out for wellbeing of them. It is observed
that severity of patient medical condition also facilitate the specific drug to be used and its
particular dosage which is suitable for them to become disease free.
People should remain aware about such conditions and prefer consultation of physician
immediately otherwise severity occurs. There are various kinds of risk factors that are associated
with cerebral ischaemic brain damage including atherosclerosis, high cholesterol, atrial
fibrillation, prior heart attack, sickle cell anaemia, clotting disorders, congenital heart defects and
high blood pressure. However, it is required to focus regular lifestyles to improve it by taking
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advice for physicians to avoid such disorder. It is favourable to adopt regular physical exercise,
yoga, balanced diet intake etc. to remain healthy by avoiding occurrence of severe health
problems.
Question 2
Please read the following review:
Anti-Amyloid-b Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise.
(Christopher H. van Dyck, 2017). Use this paper and additional references to critically
review the potential of disease-modifying immunological drugs in the treatment of
Alzheimer’s disease.
The Alzheimer’s disease can be defined as a progressive disease which was caused by brain cells
to waste away (degenerate) and die. It can be consider as a specific one health problem of
dementia which is a continuous reduction in thinking, behavioural and social skills that is
responsible for disrupting a person’s capability to function in independent manner. However, it is
essential for care practitioners to focus on actual cause behind Alzheimer’s to provide
appropriate medications and treatment (A McKenzie and et. al., 2017). It involves various kinds
of symptoms such as memory problems including repeated statement and questions over & over
and forgets conversations, appointments or events, as well as not remembering them later.
Basically, it includes the sign of routinely misplace possessions, often putting them in illogical
locations and get lost in familiar places. A person suffering with Alzheimer’s eventually forget
the names of family members and everyday objects along with facing trouble to find out right
words to determine objects, express thoughts or take part in conversations. This health problems
has several other symptoms like thinking & reasoning, making judgements & decisions, planning
& performing familiar tasks and certain changes in personality & behaviour involving
depression, apathy, social withdrawal, mood swings, irritability & aggressiveness, changes in
sleeping habits, wandering, loss of inhibitions and delusions including believing something has
been stolen. Other signs consist preserved skills and a person forget that when to see a doctor or
forget to take medicines on time.
This problem is caused due to number of factors such as combination of genetics, lifestyle
and environment components that are responsible for affecting brain over the time. It involves
various risk factors which facilitate the occurrence of Alzheimer’s disease including age, family
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history & genetics, Down syndrome, sex, mild cognitive impairment, past head trauma, poor
sleep patterns, lifestyle & heart health and lifelong learning and social engagement. However,
Alzheimer’s disease may acquire several complications like communicate in way of
experiencing pain, report symptoms of other illness, follow a prescribed treatment plan and
notice or define medication side effects. It involves other complications such as inhaling food or
liquid into lungs i.e. aspiration, pneumonia & other infections, falls, fractures, bedsores and
malnutrition or dehydration. It is necessary for care professionals to communicate to public in
regards to more effective as well as efficient preventive measures such as exercise on regular
basis, intake balanced diet with fresh produce, healthy oils and foods low in saturated fat
(Quinlan and et. al., 2017). It contains to follow treatment guidelines for managing high blood
pressure, diabetes and high cholesterol and if having habit of smoke then immediately consult
from doctor to quit smoking. Meanwhile, it is favourable for people to take care of their daily
routine including lifestyle to avoid risk of various health problems like Alzheimer’s for
remaining disease. It is necessary for medical practitioners to enhance the knowledge level of
people about prevention methods and strategies which facilitate to boost up entire health of
population.
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Figure 2: Prospects for strain-specific immunotherapy in Alzheimer’s disease and tauopathies
(Source: Prospects for strain-specific immunotherapy in Alzheimer’s disease and
tauopathies, 2018)
By considering the research article, it has been analysed that amyloid hypothesis of Alzheimer’s
disease holds about the accumulation of amyloid-β (Aβ) peptide leads to synaptic dysfunction,
neuro-degeneration and ultimately symptoms. It includes the focus on developing treatment
methods or modified medications which work against the amyloid-β (Aβ) peptide in order to
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make patient cure as soon as possible. However, it had been evaluated that there are number of
treatments available for patients suffering from Alzheimer’s in which most of them are currently
used for wellbeing of people. It is observed that mots extensively approaches like anti-Aβ
therapeutic approaches, various treatments methods are developed such as immunotherapy that is
passive immunisation via administration of exogenous monoclonal antibodies (mAbs) in specific
manner. However, it is analysed that trial of this medication face failure as well as confusing
outcomes due to which some important clues were identified by medical researchers. It includes
the review of summarising experience of the study in terms of gathering evidence for applying
the same as clinical trials to achieve actual findings (Calderón-Garcidueñas and et. al., 2016). It
is favourable to consider gathered important clues in order to examine major issues with safety
i.e. amyloid related imaging abnormalities. It has been analyse that the mAbs differ considerable
with respect of their epitropes as well as conformations of Aβ that they recognise including
monomers, oligomers, protofibrils and fibrils. These are some of consequences which are also
required to be considered by researchers at the time of targeting various kinds of species. It is
observed that fresh trials are favourable in terms of evaluating treatments at prodromal and
preclinical stages.
On the other hand, it has been analysed that the active immunotherapy has an advantage of long
terms antibody manufacturing from short term drug administration at limited cots. It includes the
fact that immune response may be inconsistent or lacking where this drug is helpful to develop
antibodies in terms of fighting with abnormalities created in human body to secure it from
harmful diseases. However, it consist several drugs or medicines that plays an important for
improving condition of Alzheimer’s’ disease. Initially, Bapineuzumab is known as humanised
immunoglobulin (Ig) G1 anti-Aβ mAb, that get binds the five N-terminal residues and clears
both fibriliar as well as soluble Aβ. It can be consider as first mAb for entering human testing
after termination of AN1792 trial (Quek and Hill, 2017). In addition to this, other compound is
Solanezumab is a humanised IgG1 that binds the mid domain of Aβ along with increasing
clearance of monomers. It has been analysed that mAb targeting Aβ has demonstrated beneficial
efficacy which was founded in several studies. It is observed that there are no significant
differences were founded in terms of typical primary outcome measures including ADAS-Cog,
ADCS-ADL or CDR-SB. However, it is necessary for physical to focus on various kinds of
treatments considering their evidences in order to implement them for treatment of an individual.
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It is required for them carefully make decision of providing specific medication for wellbeing of
a person.
Question 3
Describe with examples the two main approaches to personalised medicine based on genetic and
metabolic profiling and give examples of the use of each approach
Personalised medicines can be defined as a kind of medical treatment in which individualised
characteristics are responsible to make decision making about every patient. It includes
evaluating overall features of an individual such as their genetic information, indicated
symptoms, lifestyle and other habits in order to make decision making of medication provided to
them for their wellbeing. Basically this approach is responsible for providing person specific
treatment to a person in regards to actual health problem along with respective factors that are
consider delivering appropriate care services for their better health. However, the personalised
medicine approach is based in scientific breakthrough in understanding of the way person’s
unique molecular and genetic profile make them susceptible for several diseases (Almeida and
Kolarich, 2016). It has been analysed that it is an effective approach for every individual because
it is based on specific features of human body and symptoms show by them. Such techniques are
favourable to enhance the capability of predicting which medical treatments that they are safe as
well as effective for every sick individual. However, it is also beneficial in terms of evaluating
the clinical practices and treatment procedures which are not suitable for a person that can be
avoided by care practitioners. It will facilitate to avoid chance of occurring complications along
with delivering accurate medical facilities for their wellness.
For example, personalised medicine for a cancer patient includes Herceptin which is used to
treat female breast cancer for individuals who express high levels of HER2 whereas Gleevec
utilised for chronic myeloid leukemias (CMLs) for inhibiting tyrosine kinase (Narod, 2018).
For instance, In Melanoma, the BRAF is known as a human gene which is responsible for
development of protein called B-Raf that engaged in sending signals inside cell in order to direct
cell growth and it is indicated in mutated in cancers. It includes Vemurafenib only works for
treatment of patients having cancer positive for V600E BRAF mutation. It has been nlaysed that
around 60% of individual with melanoma have BRAF mutation and 90% of those suffered from
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BRAF V600E mutation. However, personalised medicine is favourable for specific patients in
order to become disease free.
Figure 3: Personalised medicine for cystic fibrosis: treating the basic defect
(Source: Personalised medicine for cystic fibrosis: treating the basic defect, 2020)
On the other hand, it has been examined that personalised medicine is known as an extension of
traditional approaches in order to understand actual condition of an individual along with their
needs for providing correct treatment to them. This technique contains various kinds of equipped
tools which are more precise through which care professionals become capable to select accurate
treatment or therapy protocol that is based on specific molecular profile of a patient. Basically, it
is helpful in terms of reducing harmful side effects along with ensuring a more successfully
gained outcome but this can be also contains costs with a trial-and-error approach to treatment of
particular health issue (Cozzolino and et. al., 2019). It is a suitable approach for a person to gain
treatment according to their specific metabolic activity and genetic characters in order to make
tem disease free. Meanwhile, it has been evaluated that personalised medicine has efficiency of
changing way of thinking in context of determining as well as managing health issues
accordingly. It includes the fact of already having an exciting impact of both clinical
investigation and patient care along with its benefit of affecting growth of understanding and
technologies improvements.
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Personalised medicine can be known as multi-faceted approach for patient care which is
responsible for only the increasing accuracy of diagnosis and treatment of particular disease. It is
helpful to physicians for analysing the actual body condition and its needs regarding recovery
according to which they can make appropriate care plan including clinical practices as well as
medications for welfare of patient. However, this approach provide support to medical
practitioners as it offers the potential for detecting health problem at an earlier phase the it
becomes more easier to provide much effective treatment to make a patient healthy. The
approach of personalised medicine consist number of factors which must be followed for
delivering appropriate medical facilities to solve problem of health issue. It involves risk
assessment, prevention, detection, diagnosis, treatment and management which must be
considered by physicians while using personalize medicine approach in order to render effective
care services for wellness of people (Ryden and Lewis, 2019). Initially, it includes the risk
assessment which contains the criterion of genetic testing for revealing predisposition for
specific health issue. Secondly, prevention involves the practice of conducting evaluation of
lifestyle and behavioural aspects in order to establish effective treatment intervention in terms of
preventing disease. Thirdly, the next factor is to carry out detection of disease of particular health
problem at molecular level which is effective to deliver accurate treatment services. However, it
involves diagnosis method which consist accurate diagnosis of specific disease that enable
physician for making individualised treatment strategy to increase patient experience
respectively. In addition to this, treatment process includes improved outputs with the help of
targeted treatments and decreased side effects for gaining improved patient outputs. Moreover,
the final element is management which involves the criterion of active monitoring of treatment
response as well as disease progression, this factor is very important because it is favourable to
make sure that treatment carried out was correct or the time to make necessary changes in care
plan by changing medication or therapy in order to avoid complications. Meanwhile, other
problematic aspects can be evaluated for treating on time to maintain better health condition
treatment.
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Question 4
Immunotherapies for cancer have the potential to change the course of many cancers. Critically
discuss monoclonal antibodies, checkpoint blockades and chimaeric antigen receptors as
strategies for the development of cancer immunotherapies with named examples.
Immunotherapy can be defined as a treatment method through which immune system become
strong enough to fight against cancer. It includes that various kinds of immunotherapies such as
immune checkpoint inhibitors, T-cell transfer therapy and monoclonal antibodies which can be
used by physicians in order to treat the problem of cancer in people. However, it has been
analysed that immune system become capable to lowering growth of cancer cells but they have
ability to avoid destruction by immune system by several ways (Gotwals and et. al., 2017). It
involves that cancer cells have genetic changes which are responsible for making them less
visible in front of immune system. In addition to this, they have proteins on their surface which
play role to switch of immune cells and they can change the normal cells around tumour so that
they interfere with how the immune system responds to cancer cells. Moreover, the
immunotherapy is much effective as well as efficient to help immune system in order to cat in
better way against cancer to treatment cancer patients more appropriately. It is favourable for
care professionals to utilise accurate immunotherapy in terms of treating cancer problem among
people to make them disease free respectively. There are various kinds of immunotherapies
which are given below.
Figure 4: Immunotherapy
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(Source: Immunotherapy, 2020)
Immune checkpoint inhibitors: This can be consider as drugs which has efficiency of block
immune checkpoints. It includes the checkpoints which are normal section of immune system
and keep immune response from being too strong. However, it is much effective as well as
efficient technique which can be used by medical practitioners in terms of delivering care
services. In addition to this, physicians should evaluate the cause of cancer among cancer
patients to provide this treatment. It will provide support to treat the health issue of cancer
effectively to make an individual wellbeing.
T-cell transfer therapy: This can be described as a type of treatment process that is used for
cancer patients to treat them. It involves the effective clinical treatment which is helpful boosting
up the natural capability of T-cells of human body in order to fight with cancer. Meanwhile, this
treatment procedure is supportive because it engages criteria that immune cells ate taken from
the tumour of patient which are considered as most active and effective against cancer (Sahin
and Türeci, 2018). However these are selected to get changed in the laboratory in respect of
facilitating better attack the cancer cells to destroy them for improving health condition of
patient. It also contains the action of growth in large batches and put back into human body with
the help of needle in a vein then these immune cells are much potential to fight with cancer. In
addition to this, it has been analysed that T-cell transfer therapy may also be called adoptive cell
therapy, adoptive immunotherapy or immune cell therapy. It is known as much effective therapy
because the immune cells developed in laboratory have improved potential to fight with cancer
cells in efficient way. It is required for professionals to use this therapy for making cancer
patients disease free accordingly.
Monoclonal antibodies: The method of monoclonal antibodies refers to a treatment procedure for
cancer patients in which immune system proteins developed in a laboratory which are produced
for binding for particular targets on cancer cells. It includes the role of monoclonal antibodies as
some of them are responsible for marking cancer cells so that they will be better observed in
order to get destroyed by attack of immune system. However, these monoclonal antibodies are
known to be a kind of immunotherapy and these monoclonal antibodies are also called as
therapeutic antibodies.
Treatment vaccines: The treatment vaccines can be defined as a type of clinical treatment which
is applicable of cancer patients in order to solve their health problem for achieving their better
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health. It includes it includes the working method of this process is to work against cancer with
the help of boosting up response of immune system in respect of cancer cells to destroy them. It
has been analysed that treatment vaccines are known to be different from the ones those support
in terms of preventing the health issues. Moreover, this treatment can be used by medical
practitioners for making them healthy via solving their problem of cancer in effective manner.
Immune system modulators: This can be defined an important method of treatment which is used
by medical professional in respect of cancer patients to treat their disease. It includes the process
of enhancing the immune of response of human body to take action against cancer. However, it
is observed that few of these agents plays an essential role to affect specific parts pf immune
system whereas others affect the overall immune system in a general context. Meanwhile, the
way of improving efficiency of immune system is much effective so that it can attack cancer
cells more effectively which facilitate to improve the health condition of patient.
Considering the above immunotherapies, it has been evaluated that they have efficiencies to deal
with problem of cancer for wellbeing of patients (Lim and et. al., 2018). It is necessary for
medical professionals to carefully diagnose the cause and symptoms of a type of cancer in order
to select more appropriate immunotherapy for implementation. However, it is very important to
apply correct immunotherapy because complications can be occur in cancer condition which is
very difficult to be treated by doctors. Cancer is itself a very complicated disease due to which
specialist should
use the immunotherapies in accurate way. Moreover, the cancer problem may also treated with
the help of surgery, chemotherapy or radiation therapy.
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References
Books and journals
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