Alzheimer's Disease Case Study

The discovery process is the preliminary research that an organization or research team will engage in before they even begin to look at a new drug on a molecular level. “The discovery process includes the early phases of research, which are designed to identify an investigational drug and perform initial tests in the lab” (PhRMA, 2015). In order for the researchers to know where to start with trying to create a new cure or treatment, they first have to do an in depth analysis of the disease so that they can fully understand it.

During Phase 1, sufficient information about the drug’s pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies.

This paper reviews the use of cognitive rehabilitation treatment of early stage of dementia Alzheimer’s type. The case study examines a 72 year old male patient diagnosed with early stage dementia of Alzheimer’s Type. This study used visual imagery, as well as cues and expanding rehearsal during the cognitive rehabilitation. The evaluation of cognitive rehabilitation treatment included the psychological, physiological, neurological assessments and self-reports. Results

One contributing factor is the cost of research and development required to bring a new drug to market. In order to be approved by the FDA, a drug must go through phase 0, I, II, and III processes. Phase 0 involves animal testing, phase I is small scale clinical studies to determine safety, phase II is clinical studies to determine effectiveness,

Animal Pharmacology and Toxicology preclinical data is necessary to assess whether the drug is safe for initial testing in human. Manufacturing information that consists of the make up, the manufacturer itself, stability, and controls used to manufacture the drug product. And clinical protocols and investigator information gives detailed protocols for clinical studies to assess whether the first phase trials will expose patients to unnecessary risks and obtaining informed consent.

The first step in developing a drug is pre-clinical testing. The experimental drug is tested in a laboratory and in animal studies. The drug has to meet safety standards and show potential for being a new drug. If this criterion is met, the drug moves on to the next phase. Phase 1 is concentrated on making sure the drug is safe to use on humans. This is the first time the experimental drug is used on people. Different measures of dosages of the drug are given to a small number of the volunteers. This allows the researchers to be able to measure the body’s response to the drug. The things they measure include how the drug is absorbed, its duration in the bloodstream, and what dosage levels are safe and well accepted by the body. If the experimental drug is deemed safe, it passes on to Phase 2 (Phases of Development, par. 6-7).

Earlier research was done on the inhibition of amyloid β, but a relatively new approach is to find inhibitors for acetlycholinesterases enzyme (AChE). The action of AChE results in the blockage of transmission of acetylcholine (ACh), hence hyperphosphorylating the tau protein which affects the breakage of amyloid precursor protein(APP), which firther results in the increase in amyloid β. The binding of AChE causes decrease in the binding of ACh to muscarinic recptor and nicotinic receptors (Francis, Palmer, Snape et al., 1998). A recent study has shown that ACh does not only have cognitive functions, it regulates the

Structural and functional neuroimaging such as MRI is a sensitive and accurate tool to differential diagnosis between AD and FTD phenotypes as

In 1984 the criteria for diagnosing Alzheimer’s was developed by the Alzheimer’s Association. These three levels of diagnostic certainty were: Possible, Probable, and Definitive. In the Possible AD level, symptoms were not typical, but other disorders were ruled out. For example, it could be diagnosed if the patient had another illness, as well as with symptoms of dementia. The next level is Probable AD. In this level of criteria, the diagnostic evaluation excludes other causes of diagnostic decline. In addition to this, the historical pattern of functional and behavioral disturbances was noted. With these techniques, doctors were able to diagnose with an 85-95% accuracy. The last level was called Definitive AD. Within in this level, an autopsy was performed and the examined brain tissue revealed

HDAC inhibitors are classified into 4 main chemical families. 1. Carboxylic acids- eg Sodium butyrate, valporic acid, 4phenylbutyrate acts on Class 1 HDAC. 2. Hydroxamic acid- eg: Trichosatin, SAHA acts on Class 1 and 2 HDCA. 3. Benzamide group- eg: MS275 acts on Class 1 HDAC and 4. Cyclic tetrapeptides- Tapoxin.(15) Researches have focused mainly on class 1 and class 2 HDACi as treatment option for cognitive enhancement in AD.(21-23) The studies conducted on mouse models with AD related neurodegeneration treated by sodium butyrate(24) (Class 1 HDACi) showed rescue of cognitive functions, by acting through HDAC2 inhibition. The same models treated with SAHA, TSA (Class 2HDACi) and valporic acid (22, 23)(Class 1 HDACi) showed contextual fear and memory loss abolished.(15, 25) Also studies have shown HDACis successfully used as cognitive enhancers in invertebrates. (15)

High throughput screening (HTS) is essential in the process of finding a potential drug candidate, and automation is key for a good screen both in terms of robustness and reproducibility.

Recent working experience for 21 months as a study coordinator at the cancer centre of Seoul National University Hospital has given me a greater passion for expanding my career of proficiency and growing my expertise in pharmaceutical research area. This experience also led to me learning much about not only the patients journey from diagnosis to chemo/radiotherapy but also whole process of clinical trials. I am familiar with a clinical trial protocol,

The aim of this study is to bring awareness to Alzheimer’s Disease. It is important noting that Alzheimer’s disease does not only affect the patient but also their family and caregiver. This research was conducted at St. Josephs Hospital Medical Nursing Home. We selected 10 medically diagnosed Alzheimer’s patients. We divided the patients into 2 groups. The first group consisted of patients that had a lot of moral support and affection from their families. In this group was also the grandmother of one of the contributors to this paper. The second group consisted of patients that do not receive moral support or have not seen their family for a long time.

As mentioned in class, as well as in the required Krishna (2008) article, the drug development and approval process is an extensive and costly endeavor. The goal of experimental medicine is to increase the efficiency of drug development by providing a better understanding of the drug’s mechanism(s) of action, dose response, efficacy, and safety, allowing the process to be accelerated for the most promising and efficacious candidates (Krishna, Herman, & Wagner, 2008).

The various lead compounds can be initially tested and virtual screened by high-throughput screenings (HTS) to evaluate their properties in biochemical reactions, and then the lead compounds will be optimized through altering their molecular structure. Several physicochemical properties and pharmacokinetics properties of the lead compounds will be established, such as lipophilicity, solubility, ionization, molecular size and H-bonding. The process of lead optimization can not only improves lead compounds’ physicochemical properties, but also makes them more effective and safer. Simultaneously, medicinal chemists begin to consider about chemical manufacture and control (CMC), such as synthesis, formulation, delivery mechanism and large-scale manufacturing. The optimized lead compound could ultimately evolve into a new drug candidate. The function of pre-clinical research is to assess all of the physicochemical and pharmacokinetics parameters prior to clinical trials. Or, to put it another way, whether the lead compound is safe enough to move on to clinical trials depends on pre-clinical research. For example, pharmaceutical researchers carry out pharmacokinetics (PK) testing which involves absorption, distribution, metabolism, excretion (ADME), and toxicology to estimate the safety starting dose through in vitro and in vivo testing. After these complicated and rigorous pre-clinical trials, scientists have