Michael Mullan Articles
FDA approves two new treatment medications
Two new types of Alzheimer’s treatment medication have been recently approved by the FDA. The new drugs are memantine and cholinesterase inhibitors. Both work on cognitive dysfunction, which is one of the most debilitating outcomes of the disease.
Alzheimer’s disease and cognitive function
One of the consequences of Alzheimer’s is that brain cells die and the connectors, or synapses, between cells become more damaged as the disease progresses, triggering worsening cognitive functioning. The patient’s ability to learn and remember is severely hampered. Medications currently available are not able to reverse the damage caused by Alzheimer’s, although they do offer hope for calming the symptoms.
Memantine and cholinesterase inhibitors work on the neurotransmitters
Neurotransmitters help neurons communicate. Alzheimer’s disease hinders this process by damaging the synapses. The new drugs address this problem in different ways. Memantine regulates glutamate, a key neurotransmitter that impacts learning and memory. If glutamate attaches to the surface of cells, calcium can enter. When Alzheimer’s disease is present, the amount of calcium that enters the cell reaches a level that intensifies the cell damage. Memantine works to decrease the calcium entering the cell. Cholinesterase inhibitors slow down the process whereby key neurotransmitters are damaged.
Typical Alzheimer’s disease treatment methodology
A treatment protocol is established for the Alzheimer’s patient by the doctor depending upon a number of factors. These include:
• The patient’s medical history and current health assessment
• How far the disease has progressed
• The patient’s ability to tolerate medicines and treatment therapies
• Prognosis for the future
• Preferences of the patient and/or guardians
The only way to determine the effectiveness of new treatment medications is to safely introduce the drugs to people and then document the outcomes. Clinical trials involve a carefully regulated application of new drugs to patients which yields invaluable answers to the questions of a drug’s effectiveness. It is the paramount way for researchers to develop new drug therapies that can reverse, or at least halt, the ravaging effect of Alzheimer’s, and ultimately prevent the disease from occurring.
The question over the exact causes of Alzheimer’s disease has long been at the heart of research into the condition that affects so many of our loved ones. In a recent article by Lauren Horne, she details new research into the cause and possible treatment of Alzheimer’s disease. The study that was published in June 2014 in “Nature Medicine,” the well respected medical journal, examines the theorized effect of reactive astrocytes in the development of the disease. The study was carried out under the auspices of Drs. C. Justin Lee and Daesoo Kim in Korea and their paper was published with the title: “GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease.”
As described in the title of the paper, the focus of this research was centered around the effects of the reactive astrocytes. In particular, Lee and Kim pointed to the fact that these reactive astrocytes are often found in large percentages in the brains of patients with Alzheimer’s disease and are known to produce GABA, a neurotransmitter inhibitor. As they found that the reactive astrocytes were producing the GABA through Monoamine oxidase B(MAO-B), an enzyme that then passed on the GABA into the system through the BESt1 channel, they decided to target the B(MAO-B) in their testing.
What they found was that when they used the Parkinson’s disease drug Selegiline as an inhibitor to bring the levels of the GABA back to more normal numbers, they were able to succeed in slowing down the firing of neurons in the brain. In their tests that they carried out on mice with Alzheimer’s disease in the labs, those subjects who received the inhibitor treatment exhibited signs of improved memory that were consistent with their theory.
Unfortunately these results did not leave any lasting changes on the mice as the effect of the drugs wore off. However, to all those who are invested in finding a cure for Alzheimer’s disease, this study has provided valuable knowledge and new insights that may soon lead to a treatment.
Manipulation of Reelin signaling offers hope for reversing cognitive function of Alzheimer’s patients
A new study from Cell Biology Department scientists at the University of Barcelona working with laboratory mice sheds new light on the role that the protein Reelin plays in preserving plasticity in adult brains and restoring lost cognitive function. These findings were recently published in the periodical, Nature Connections, and are critical to the efforts to prevent and treat Alzheimer’s disease.
In spite of years of research seeking to locate the cause of Alzheimer’s disease, scientists still do not know the cause of this neurodegenerative ailment. However there are some known structures that appear to have a significant role in causing loss of cognitive function, neuronal death and decrease in synaptic functioning. These structures are amyloid plaques and neurofibrillary tangles. The new study reveals that when levels of Reelin were increased in the brain of laboratory mice with Alzheimer’s, cognitive loss was reversed. Further, it was confirmed that Reelin diminishes amyloid deposits and postpones the development of amyloid-beta fibril in vitro.
The role of Reelin in controlling tau protein and the amyloid precursor protein was already known, but the full extent of Reelin’s role was undiscovered. So, the researchers focused their efforts on analyzing Reelin’s role. With this new study, researchers working on prevention and treatment methodologies have a new comprehension of the bond between these two proteins and Reelin’s role in regulating them. The study proves that an increase in Reelin is beneficial to reversing the effects of Alzheimer’s disease.
Researchers discovered the nature of the interaction between Reelin in vitro and the peptide AB42, a lethal peptide responsible for the accumulation of senile plaques and formation of fibril. In vitro tests on mouse models revealed that Reelin was functioning to reduce plaque and delaying fibril formation. With these findings, researchers offer Reelin as a promoter of adult brain plasticity and protective agent for neurons. Future research will concentrate on identifying chemical composites that can stimulate Reelin signaling.
Article Written by Dr. Michael Mullan
There has long been controversy over whether women or men are most affected by Alzheimer’s disease. Decades ago the perceived wisdom was that Alzheimer’s affected women more than men because women live longer than men and Alzheimer’s is a disease of aging. However, this apparent sex discrimination was challenged in subsequent studies and more recent investigations suggest that women may be at greater risk than men on an age matched basis. However, even this is controversial and may differ between populations.
For instance, some American studies report equal rates between men and women whereas European ones report a sex difference with more women than men being affected. However, several incidence studies looking at new cases of Alzheimer’s suggests that women are more readily affected than men.
Many reasons have been offered as to why there may be sex discrimination by Alzheimer pathology. One idea is that loss of sex hormones after menopause is particularly detrimental to the human brain. It’s known, for instance, that sex hormones can regulate Beta amyloid production. Cell culture studies show that estrogen and testosterone can mitigate the production of amyloid, one of the central features of Alzheimer’s.
Sex hormones may play other roles as well as regulating the amount of amyloid produced. They may have a role for instance in the breakdown of amyloid and the clearance of amyloid by other mechanisms in the brain. It’s also possible that progesterone have a protective role in the brain. Evidence suggests that after difference insults to the brain, progesterone can be protective.
While all of these observations on the sex differences have been very valuable, no therapy has yet emerged based on hormone replacement. In fact, key studies looking at hormone replacement in post-menapausal women have not shown any beneficial reduction in the risk for Alzheimer’s disease. At best, hormone replacement therapy has shown mixed results in relation to any protection against Alzheimer’s disease. Interestingly, any evidence that sex hormones are helpful in Alzheimer’s are restricted to prevention strategies rather than treatment strategies. In other words, it looks as if prolonged exposure to sex hormones may influence the rate of Alzheimer’s disease; but, once the disease is established, sex hormone therapy is not clearly protective.
So, although there is evidence that Alzheimer’s disease does indeed discriminate against women, the underlying causes are still uncertain and simple hormone replacement therapy may not be the best answer. However, more broadly, Alzheimer’s discriminates against both genders once natural hormone levels start to fall in the later decades of life.
Much more work needs to be done to understand these effects and to ask whether any of these findings can be turned into new clinical treatments for the disease.