CERE-110 in treating Alzheimer’s disease

Abstract

Alzheimer’s disease is simply a progressive condition that has been established to destroy the connection between the cells in the brain. It kills these cells which in the process affect the function of the brain. As the cells die in the outer layer of the brain, it gradually shrinks, and further, the spaces in the brain get significantly larger. Brain damage results into numerous problems with the judgment, memory, behavior and even intelligence. Alzheimer’s is thus a common type of mental decline or dementia among the aged population. There is the need to have a timely intervention targeting various non-genetic risk factors that are believed to be critical in the Alzheimer's diseases. A major risk factor that has been established to be linked closely with increased rates of Alzheimer's is the old age, and it is common for people who have attained the age of 65 and above. Studies have shown that family history and the genetics are associated present a higher risk level particularly when the parent or the siblings have this illness. The current research, therefore, aims to assess the effectiveness and importance of CERE-110 in the management of Alzheimer's disease. The study was conducted on a sample population of about ten patients diagnosed with Alzheimer's disease. Further, part of the population under analysis got subjected into CERE-110 where it was injected into their brain via a surgery while the other part went through a "placebo" surgery and no medication was injected. The hypothesis of the study is stated as follows, using the CERE-110 drug for the transportation of nerve growth cells to the inside of the brain to restore degenerated neurons and protect them will stop or slow down Alzheimer’s disease’s progression.

Introduction

Various studies carried out over the years have established that Alzheimer’s disease is one of the greatest public health risks that has continued to affect the population particularly of people above the age 65 (Zanetti, Solerte & Cantoni, 2009). Individuals diagnosed with Down syndrome have been reported to have a higher risk of developing Alzheimer’s, and on most occasions, the symptoms are visible about 10-20 years earlier to those individual with Down syndrome than to those with no such condition. Evidently, sex is also a greater risk factor where it was confirmed that women have the highest risk as far as Alzheimer’s disease is concerned than men since they live longer. According to Zanetti, Solerte & Cantoni, (2009), individuals diagnosed with Alzheimer’s disease often have a quality of life provided that they can access a quality care. According to a study done by Alzheimer’s Disease International, approximately 44 million people are living with Alzheimer’s disease across the world, but only one out of every four individuals have been able to be diagnosed (Alzheimer’s, 2015). Additionally, about one in every nine people has this illness based on a study that was conducted by Alzheimer’s Association in the US. Further, Alzheimer’s is most prevalent in the Western Europe but least prevalent in various areas of the Sub-Saharan Africa. Current studies have confirmed that Alzheimer’s disease is among the top causes of disability sand this is common among the elderly individuals. Alzheimer’s Association in the year 2013, established that about 3 million people of ages between 85 and above had Alzheimer's and one-third of the entire citizens of America of ages between 85 and older had Alzheimer’s (Hurd et al., 2013). 

Today approximately 5.3 citizens of America are believed to suffer from this condition, and it follows that if nothing is done immediately, the figure might rise rapidly to about 16 million cases by the year 2050 based on a report from research carried out by Alzheimer’s Association. Further Alzheimer’s Association established that this disease is the 6th common cause of deaths throughout the US where about one on three elderly individuals often die with the diseases (de Flores, La Joie & Chételat, 2015). The life expectancy of a person diagnosed with Alzheimer’s disease is approximately 4-8 years. According to Zanetti, Solerte & Cantoni, (2009), for the US citizens with Alzheimer’s disease, two in every three patients are females. On the other hand, the disease is also common based on race where in the year 2016, its racial makeup (Tejada-Vera, 2013). Alzheimer’s is thus a common type of mental decline or dementia among the aged population that has continued to affect their quality of life of people especially those individuals with advanced age. The study, therefore, seeks to test the importance and effectiveness of CERE-110 as the new form of treatment to the illness with the aim of improving the patient’s well-being and protect these patients from potential further degeneration.

Objectives

CERE-110 is one of the major areas to be focused when it comes to enhancing the condition of these individuals and treating Alzheimer's disease (Arvanitakis .et al, 2007). Therefore, the objective of the study is: To analyze the benefits and effectiveness of CERE-110 in managing the Alzheimer’s disease

Hypotheses

The hypothesis of the research is as shown below: Using the CERE-110 drug for the transportation of nerve growth cells to the inside of the brain to restore degenerated neurons and protect them will stop or slow down significantly the Alzheimer’s disease’s progression.

Background

According to Campbell-Taylor et al., (2014), the elderly who had experienced severe head trauma tend to have higher risks of developing Alzheimer’s disease. Studies have found that the health and lifestyle comprise of the core risk factors for this illness where individuals have increased the risk to develop the condition as influenced by these two factors (Zanetti, Solerte & Cantoni, 2009). For instance, lack of physical exercise is closely linked to an increased risk of obesity, high blood cholesterol in addition to the high blood pressure. In addition to this, research has shown that exposure to second-hand nicotine smoking and poor dieting increases the chances of developing this disease (Zanetti, Solerte & Cantoni, 2009). For many years, there has been contemplation for the use of nerve growth factors to manage and cure degenerating basal forebrain cholinergic neurons as one of the methods to control Alzheimer’s. According to Tejada-Vera (2013), there has been a lack of an efficient manner to make this successful until recently when CERE-110 was developed. Research has proven that CERE-110, which is an associated virus-based gene is suitable for managing the Alzheimer’s disease. According to Bishop et al., (2008), NGF transgene when delivered into the brain of a patient diagnosed with Alzheimer’s disease is reliable and precise in treating the Alzheimer’s condition. The distribution of NGF transgene is made possible through varying the CERE-110 doses (Bishop et al., 2008). The majority of the dementia cases about 70 percent have further been argued to be caused by Alzheimer’s disease. About 1 in every ten individual of ages between 65 and above years and 1 in every four people of ages between over 85 years have dementia related to Alzheimer’s disease (Campbell-Taylor et al., 2014). Alzheimer’s disease tends to cause lapses in memory which deteriorates to the point in which those living with the disease are unable to look after themselves and need to go into 24-hour care. There is currently no precise treatment for this illness that has been confirmed suitable to treat the disease altogether. According to Campbell-Taylor et al., (2014), gene therapy has been used for long in managing Alzheimer’s disease. CERE-110 can be seen as a gene therapy designed to introduce a particular genetic material into the brain cell to compensate the abnormal gene or even to make some protein that is beneficial (Arvanitakis et al., 2007). CERE-110 is an investigational biopharmaceutical medication that is premeditated specifically to refurbish all the destroyed cholinergic cells and at the same time save them from harm and possible degeneration (de Flores, La Joie & Chételat, 2015). CERE comprises a vector containing the gene for human nerve growth factor. The drug will serve as a carrier for delivering an NGF to the brain. CERE-110 is simply a gene therapy strategy used for the neuroprotective cure of Alzheimer's (Bishop et al., 2008). According to Arvanitakis et al., (2007), the foundation of this approach can be traced to a research establishing that NGF can slow neurodegeneration related to age particularly in a mouse model and rhesus monkey. The method has been used severally in small clinical trials since the year 2000. CERE-110 was created by Ceregene, which was bought by Sangamo BioSciences in 2013 (Bishop et al., 2008). 

A pilot study of the previous form of NGF gene therapy which was delivered through genetically engineered autologous fibroblasts established safety and hints for a potential long-term benefit for locally produced NGF (Arvanitakis et al., 2007). In the year around 2004 and 2010, there was another two-year, open-label Phase 1 trial that was carried out in San Diego and Chicago to investigate the safety, tolerability, and biological activity of increasing doses of CERE-110. The substance was delivered directly by bilateral stereotactic surgery into ten individuals who have been confirmed to suffer from the mild and moderate condition of Alzheimer's disease (Bishop et al., 2008). The study reported that CERE-110 is clearly the safest forms of Alzheimer’s disease treatment in addition to being highly tolerated for up to two years of observation. Therefore, it can be used safely to treat Alzheimer’s disease among all people irrespective of the age, gender and race. In addition to this, a stable expression and biological activity were also reported founded on postmortem pathology (Arvanitakis et al., 2007). In the year 2009 to 2015, a multicenter, sham-surgery controlled Phase 2 preliminary trial was also carried out by the ADCS to determine the effectiveness of CERE-110 in 49 people experiencing mild and moderate Alzheimer's disease. The research was meant to test CERE-110 ability to slow decline on the ADAS-cog, NPI, and ADCS-ADL batteries and to measure efficacy on cognition, neuropsychiatric well-being, and activities of daily living (Arvanitakis et al., 2007). The experiment also confirmed that CERE-110 was highly safe and well-tolerated, but ineffective to some significant level. 

Methods

Before commencing with the tests, a drug testing will be required because the drug will have to be administered to the human subjects. The permit will, therefore, be necessary to test the drug on the human participants legally. The sample population for the study will entail individuals diagnosed with Alzheimer’s disease. The sample size for the study will be determined through the use of stratified random sampling. When using this approach, all the individuals with Alzheimer’s disease will have an equal opportunity of being included in the study. Additional, the researcher will able to ensure that the sample size was a representative and comprises of both the males and females. The sample size is big enough to gain the insight of the problem and respond adequately to accept or refute the research hypothesis. The size will further enable the research to gather different but relative efficiency of CERE-110 in managing Alzheimer’s disease. Through this sample population, the researcher will be able to analyze the effectiveness of CERE-110. The research will select about ten human subjects that have been confirmed to suffer from Alzheimer’s disease at a mild or moderate stage. One-half of the entire population under study will be introduced to the CERE-110 condition where the substance was injected into their brain through surgery while the other half population will be subjected to a "placebo" surgery and in this case, no medication was injected into the brain of these individuals. It would also be critical that the patients under study be followed carefully for not less than five months after the surgery procedure. The next step will be to locate the nucleus basalis which is simply a group of neurons in the brain that is a rich in acetylcholine that is affected by AD. CERE-110 will then be surgically injected into the nucleus basalis of the brain using a stereotactic injection. CRE-110 enters the neuron and then induces it to produce a continuous life supply of NGF. The human subject’s brain activity will then be monitored to observe the effectiveness of the drug. Laboratory in addition to various clinical procedures will also be made in order to evaluate the progressiveness of the disease.

Many limitations are expected to arise with this experiment hence the need to take them into consideration. First, a potential pitfall expected in this study is the fact that the drug might not reach its destination in the brain. Further, CERE-110 might reach the destination in the brain, but the nervous system might reject it (Bishop et al., 2008). The expected result of the experiment is that NGF will restore the function of the neuron and further protect it from potential further degeneration. Evidently, this has been established to be critical and will thus significantly reduce the severity of the symptoms and then slow the disease progression.

Significance

Based on a study carried out by Alzheimer’s Association, the overall expenditure for treating and managing the individuals diagnosed with the Alzheimer's disease in the US only was approximately 236 billion in the year 2016, and globally it was approximated to be about $605 billion (Tejada-Vera, 2013). This cost is very high and can be equated to one percent of the entire GDP of the world (Bishop et al., 2008). It points to the direction that Alzheimer’s disease is very costly and the fund could be used in the financing another critical sector to improve the well-being of the citizens. In the year 2015, the total Medicare and Medicaid spending were established to be about $154 billion meant to fund the healthcare and hospice for patients diagnosed with Alzheimer’s disease. According to Tejada-Vera (2013), Alzheimer’s Association confirmed that the total aggregate expenditure to manage and treat people of ages between 65 years and above suffering from the Alzheimer's disease is as follows, Medicaid $41 Billion, Medicare about $113 Billion and $44 from the patient’s pockets. The disease has also been associated with increased rates of emotional stress (Bishop et al., 2008). In another study carried out by NAC/AARP in the year 2009, it was confirmed that most of the caregivers in charge of patients who have Alzheimer's disease were old women and the majority of them were Hispanics and Caucasians (Hebert et al., 2013). The elderly population with Alzheimer’s disease are hospitalized thrice more often than elderly without Alzheimer’s (Tejada-Vera, 2013). 

Evidently, the cost of managing and treating the disease is very high to the individual, family and the nation. The current study aims to determine the effectiveness of CERE-110 to test its potential benefits, safety and ensure that it does not have adverse effects (Bishop et al., 2008). If it proves to be efficient and fruitful against Alzheimer’s disease, it will have to be distributed throughout the hospitals in the world for benefits of the individuals diagnosed with Alzheimer’s disease (Bishop et al., 2008). Today, no drug can be said to be efficient in the treatment of Alzheimer's disease (Gutierrez, 2014). For years, researchers have come up with several forms of drugs and treatment to manage the condition of the disease but temporarily and have also slowed down the condition’s progression. Two of the first medication that were used for these patients include acetylcholinesterase inhibitors and NMDA receptor antagonists but are not very efficient in managing Alzheimer's disease hence the need to try the use of CERE 110. According to Tejada-Vera (2013), galantamine and donepezil have been established to be significantly efficiently when it comes to the prevention of the acetylcholinesterase enzyme from breaking down the acetylcholine in the brain (Gutierrez, 2014). When the acetylcholine levels are increased there is an enhanced communication particularly within the patient’s nerve cells which in the process alleviates and stabilizes Alzheimer's disease symptoms (Alzheimer’s, 2015). Further, Memantine has been useful, and most medical practitioners used it as part of the medication of NHS cares for a severe Alzheimer's disease. The drug was helpful to those patients who were determined that they could not use cholinesterase inhibitor drugs. Memantine was confirmed to be useful and helped to enhance several symptoms associated with Alzheimer’s disease such as aggression, delusion, agitation and even aggression (Bishop et al., 2008). This medication was extensively used throughout the world and helped in reducing the rates of Alzheimer's disease, however; they were not as useful as they were imagined to be. In addition to this, all these forms of medication were very experienced and could only be accessed by few individuals who were able to purchase them. The majority of the hospitals could also not afford to buy these drugs and place them in their stock for use because they were costly. According to Bishop et al., (2008), the use of CERE-110 is believed to be cost effective and cheaper when it comes to the treatment of Alzheimer's disease where it helps the nerve cells in the brain to function better. When an individual’s nerve cells work properly, then there is a higher chance that the Alzheimer’s disease might be managed significantly (Alzheimer’s, 2015). Research has established that CERE-110 make use of a virus to transfer genes producing NGF, which is a protein with the ability to make the nerve cells healthier while at the same time protect them from dying. In ensuring that the brain cells remain more vigorous as before, possibilities of worsening conditions of Alzheimer’s disease might be reduced significantly resulting in overall improved heath condition of the patient (Bishop et al., 2008). The CERE-110 virus does not cause any illness in people implying that it is highly safe to the participants and those individual who might be willing to use it to improve their Alzheimer’s disease condition (Bishop et al., 2008). According to Tejada-Vera (2013), when fully confirmed to be efficient and suitable in addition to being safer, CERE-110 will be adopted countrywide to improve the well-being of the patients suffering from the disease. Studies have established that this will substantially reduce a cost of medication associated with Alzheimer’s disease, save the government huge financial resources and save the life (Bishop et al., 2008).

References

Alzheimer’s, A. (2015). 2015 Alzheimer's disease facts and figures. Alzheimer's & dementia: the journal of the Alzheimer's Association , 11 (3), 332.

Arvanitakis, Z., Tuszynski, M. H., Bakay, R., Arends, D., Potkin, S., Bartus, R., & Bennett, D. (2007, March). Interim data from a phase 1 clinical trial of AAV-NGF (CERE-110) gene delivery in Alzheimer's disease. In Neurology (Vol. 68, No. 12, pp. A233-A234). 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA: LIPPINCOTT WILLIAMS & WILKINS.

Bishop, K. M., Hofer, E. K., Mehta, A., Ramirez, A., Sun, L., Tuszynski, M., & Bartus, R. T. (2008). Therapeutic potential of CERE-110 (AAV2-NGF): targeted, stable, and sustained NGF delivery and trophic activity on rodent basal forebrain cholinergic neurons. Experimental neurology , 211 (2), 574-584.

Campbell-Taylor, I., James, B., Leurgans, S., & Bennett, D. (2014). Contribution of Alzheimer disease to mortality in the United States. Neurology , 83 (14), 1302- 1302.

de Flores, R., La Joie, R., & Chételat, G. (2015). Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease. Neuroscience , 309 , 29-50.

Gutierrez, A. R. (2014). The High Cost of Caregiving for Alzheimer’s Disease (Doctoral dissertation, Kalamazoo College).

Hebert, L. E., Weuve, J., Scherr, P. A., & Evans, D. A. (2013). Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology , 80 (19), 1778-1783.

Hurd, M. D., Martorell, P., Delavande, A., Mullen, K. J., & Langa, K. M. (2013). Monetary costs of dementia in the United States. New England Journal of Medicine , 368 (14), 1326-1334.

Tejada-Vera, B. (2013). Mortality from Alzheimer's disease in the United States: Data for 2000 and 2010 . US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics.

Zanetti, O., Solerte, S. B., & Cantoni, F. (2009). Life expectancy in Alzheimer's disease (AD). Archives of gerontology and geriatrics , 49 , 237-243.