The Use of BAN2401 (Aβ mAb) in Alzheimer's Disease Treatment

This assignment investigates the use of BAN2401 (Aβ mAb) in the treatment of Alzheimer's disease. The introduction provides background on Alzheimer's disease, its prevalence, symptoms, and current treatments, highlighting the role of amyloid plaques and tangles. The study proposes a six-arm clinical trial design involving 50 participants over 12 months, utilizing various dosages of BAN2401. The methods section details participant selection criteria, including age and MMSE scores, and outlines the procedures, including blood tests, MMSE assessments, and imaging. The primary outcome measure is assessed using the ADCOMS test every three months, while secondary outcomes include CDR global range and MMSE. Data analysis involves longitudinal Bayesian analysis and repeated ANOVA tests. The conclusion emphasizes the need for new treatments and the potential of BAN2401 to improve the lives of those affected by Alzheimer's disease, discussing the drug's mechanism of action and advantages.

Running head: BAN2401 (Aβ mAb) 1
Investigating the Use BAN2401 (Aβ mAb) in Treatment of Alzheimer Disease
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Investigating the Use of BAN2401 (Aβ mAb) in Treatment of Alzheimer Disease.
Introduction
Alzheimer Disease (AD) is one of the major types of dementia in Australia. Dementia is a
syndrome generally used to describe a decline of mental and cognitive ability of the brain
enough to distract with the daily life of a person(Alzheimer’s Association, 2019). There are
about 350, 000 people living with dementia in Australia of which the number is expected to
increase up to 400,000 within the next ten years. Dementia is currently one of the mental health
disease burden amounting to around 44 million people worldwide(Alzheimer’s Association,
2019). AD causes about 70% of all dementia-related problems globally and thus Australia is no
exception. AD usually affects individuals memory problems, behaviors and thinking capabilities.
During the early stages of AD, the symptoms may be minimal but when disease progress more
severe brain damages are experienced(Alzheimer’s Association, 2019). However, the rates of
which this disease progress differs from one person to another but an average human being live
up to eight years after the symptoms begin.
When an individual is affected by AD, the whole brain changes progressively. The
disease usually leads to tissue loss and nerve cell death throughout the brain affecting almost all
the functions as the brain shrink dramatically over time. Although there are no sure causes of AD
up to now, evidence shows that the tangles and plaque that develop in affected individuals while
viewed under a microscope are the prime suspects(Alzheimer’s Association, 2019). Plaques are
usually abnormal clusters of proteins that develop in between the nerve cells while tangles
consist of twisted strands of different types of proteins. These plaques usually form when certain
proteins known as beta-amyloid clump together(Alzheimer’s Association, 2019). These clumps
of cells usually damage the brain tissues by blocking the neuron signaling at the synapse or by

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activating body immune systems thus triggering inflammation and cell damage. On the other
hand, tangles destroy crucial cell transport systems usually made of proteins. This made the
nutrients and other minerals to stop moving from one cell to another leading to cell
death(Alzheimer’s Association, 2019). Therefore, most current AD treatments normally target
the tangles and plaques in order to reduce or prevent disease progression.
Although there are no definite factors that increase the chances of getting AD, various
studies have suggested different risk factors that may put an individual at higher risks. One of the
most common risk factors includes the age of a person. When individuals reach 65 years, the risk
of developing AD doubles in each every preceding five years(Parsons & Rammes, 2017). Other
risk factors include family members with AD, genetics, lack of education concerning the disease,
cardiovascular disease, mild cognitive impairment, and brain injuries. One of the earliest
symptoms of AD is memory loss. This is because AD first affects the hippocampus brain cell a
part of the brain responsible for learning(Lannfelt et al., 2014). Other symptoms include mood
changes and personality behaviors such as withdrawal from friends and family members,
difficulties in completing normal daily tasks and solving easy problems, communication
problems, confusion and trouble understanding visual images.
Due to the fact that AD is not the only causes of memory loss in humans, diagnosing AD
can be tough. Therefore, a comprehensive medical exam including family history, mental status
examination, medical history and other tests like brain imaging are usually used to determine
whether a person has AD or not(Moreth, Mavoungou, & Schindowski, 2013). Currently, there
are no absolute treatments of AD that completely slow or stop the brain damage. However,
several pharmacological therapies and medication have been produced to help improve the
disease symptoms by increasing the neurotransmitters in the brain(Galimberti & Scarpini, 2016).

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Various studies and research are being conducted to help improve the treatment of AD majorly
focusing on how to stop the brain cells death. In addition, the treatment of AD is integrated with
other support stems and use of medications that help to improve the quality of life in affected
individuals(Liu, Yang, Ke, Li, & Suen, 2016). Such treatments include treating the already
existing medical conditions, behavioral interventions that can help to increase cognitive abilities
and providing both family and patients support care teams.
This study seeks to investigate the impact of the use of BAN2401 (Aβ mAb) in treatment
of AD to improve the lives of many affected Australians. Currently, BAN2401 (Aβ mAb) is
under phase three of drug development under Biogen Neuroscience(Lemere & Masliah, 2010).
BAN2401 (Aβ mAb) is a humanized IgG1 version monoclonal antibody mAb158 which binds to
large and soluble AB protofibrils selectively(Logovinsky et al., 2016). This drug has been found
by several studies to minimize the AB protofibrils in the brain and the cerebrospinal fluid of the
tgArc-Swe mice. Besides, the drug also acts in minimizing the AB protofibrils toxicity through
accumulating these proteins in astrocytes(Logovinsky et al., 2016). Due to the fact that the
memory loss in AD and its functionality has been linked with abnormal deposits of amyloid
plaques proteins, BAN2401 (Aβ mAb) is an antibody that primarily binds to the amyloid thus
reducing and slowing the progress of the disease. As such, this drug may have a greater potential
impact, especially when used in the treatment of AD at early stages(Panza et al., 2011).
Therefore, reducing the AB protofibrils using BAN2401 (Aβ mAb) in human can help to provide
an efficient and effective approach for AD treatment that may lead to improvement of other
disease pathological processes such as inflammatory changes, synaptic block and absolute brain
damage brought by the plaque. One major advantage of BAN2401 (Aβ mAb) in its development
is its higher binding characteristics to AB protofibrils as compared to monomers(Logovinsky et

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al., 2016). This drug acts better when the patients are given before the development of plaques.
After, the development of plaques BAN2401 (Aβ mAb) can only diminish further progression
but cannot repair the damaged parts(Toyn, 2015).
Methods
Participants.
This study will include all patients above50 years old. Both females and males will be
included in the study basing on convenience sampling method. This involves selecting patients in
terms of availability. All patients selected will be given an informed consent to sign and be
educated what the research entails and why it is needed. A sample of 50 participants will be
used. The sample will be obtained from the hospital database of which any relevant patient will
be contacted if met the eligibility criteria.
Inclusion and Exclusion Criteria.
This study will include patients registered and diagnosed in the hospital with mild to
moderate Alzheimer disease using national criteria. The participant with severe AD will be
excluded from the study. Patients must be over 50 years old with no physical or any other
diseases. In addition, all participant must be under the Mini-Mental State Exam(MMSE) range of
between 20 and 30 for them to be included in the study(Schneider, 2014). Other than that, for the
participant to be fully eligible, hospital database must demonstrate that she or he has been
following up with treatment regime since diagnosis and is currently under treatment. More
preference will be put in selecting individuals who were diagnosed with AD in a period not
longer than three to four months.
Study Design

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A six treatment arms investigation design will be used for 12 months. This investigation design
has been adopted from Biogen where six arms of treatment are used which include one placebo,
five doses arms, and two regimens.
Procedure.
After recruiting and selecting the target population over a cell phone and an invitation
letter that consist of all the details of the procedure, all eligible participants will be invited to a
hospital hall meeting for briefing and confirmation. Participants who will attend the meeting will
undergo all the relevant investigation including blood tests, MMSE and imaging to confirm the
level of the AD they have(Veitch et al., 2019). After the confirmation, eligible participants will
be subjected to a six arms treatment design over twelve months. The first procedure will include
receiving a bio-weekly infusion to maintain the blind. All patients will then be subjected to the
same randomized dose throughout the period. The active doses arms for the first regimen will
include 2.5mg/kg of the drug bi-weekly, then a 5mg/kg and finally a 10mg/kg within the same
intervals. The second regimen will consist of a 5mg/kg, and later a 10mg/kg monthly for the
whole period. In order to allocate the best effective doses to various subjects, a computer-
generated algorithm will be used at each interval using the resultant AD Composite
Score(ADCOMS)(Wang et al., 2016).
Primary Outcomes Measures.
The key primary clinical outcome measures will be assessed using the ADCOMS test in each
every three months(Wang et al., 2016).
Secondary Outcome Measures.
The CDR global range test and MMSE will be used to determine the secondary key outcomes in
every three months. In addition, at the end of the treatment period, longitudinal biomarkers and

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volumetric MRI will be used to determine whether there were major impacts of the treatment or
not(Schneider, 2014). Participants will also receive other medical tests to check if there was any
side effect of the drug affecting other physiological functions.
Data Analysis.
The primary outcomes measures assessment will be analyzed using the longitudinal data
over the period with Bayesian analysis. In Bayesian analysis, statistical data are estimated using
a longitudinal distribution by applying the principles of the observed distribution(Stern, 2015).
This involves assuming a uniform distribution over the certain rage of values before distribution.
After the data will be collected the observed distribution will then be multiplied by the likelihood
function of prior distribution to obtain a probability of possible values(Stern, 2015). The
secondary outcomes measure will be analyzed using the repeated ANOVA test to compare the
valuables based on repeated observation specifically for MMSE and CDR global range
assessments for AD(Therneau, 2015). All data will then be represented using graphs and tables.
The data will also be grouped according to regimes and doses patients took. Patients with similar
doses and regimes will be categorized differently. In addition, participants will also be analyzed
according to age groups of between five years and gender. If there will be patients from different
races, the categories will be mentioned but not analyzed to allow confidentiality. The names of
the patients will be excluded when presenting the data analysis to allow patient confidentiality
and promote anonymity. After data has been analyzed, all patients record forms will be
terminated and data stored in a flash disk that has a password. After analysis, all data will be
presented as a report and the individual results will be destroyed.

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Conclusion.
AD disease has been one of the major global health concerns affecting millions of people.
In Australia, about one million families are caring for an AD and the population is expected to
increase. Due to this reason, there is a vast need for developing and investigating modern
medication for AD to increase the wellness of individuals and their families. In addition, AD
currently has no known absolute treatment except supportive therapies which only support
patients for a short period ranging from four to eight years. Therefore, investigating a newly
developing drug can help the concerned companies to finish their development in a more timely
manner before the problem becomes out of control. The development of AD disease is not well
known. However, various researchers have suggested that AD progress due to absence of tangles
and plaques that affect the brain activities and finally leading to complete brain damage .the
tangles destroy crucial cell transport systems usually made of proteins making the nutrients and
other minerals to stop moving from one cell to another leading to cell death. The plaques usually
form when certain proteins known as beta-amyloid clump together leading to damage the brain
tissues by blocking the neuron signaling at the synapse or by activating body immune systems
thus triggering inflammation and cell damage. Targeting those two causes can have a greater
impact on the development of an absolute cure.BAN2401 (Aβ mAb) is an antibody that
primarily binds to the amyloid thus reducing and slowing the progress of the disease. As such,
this drug may have a greater potential impact, especially when used in the treatment of AD at
early stages. This drug has high binding affinity to AB protofibrils and thus can be highly
effective in reducing the spread of plaques within the human brain.

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