Media Articles and Publications by Michael Mullan
Results of Aducanumab Anti-amyloid Drug Trials Published
A newly concluded clinical trial, which was recently published in “Nature,” gives added strength to the theory that utilizing antibody therapies to remove amyloid deposits from brain cells is a successful strategy for preventing Alzheimer’s disease.
Clearing Away Amyloid
The trial, which lasted for one year, included 165 subjects who were diagnosed with early stage Alzheimer’s. Early stage was defined as those with a CDR score of between .05 and 1.0. Subjects were given differing doses of Aducanumab, a monoclonal antibody developed by Biogen to remove the buildup of amyloid (A-beta) deposits from brain cells. A buildup of amyloid in the brain has been identified as one of the causative factors leading to cognitive dysfunction and ultimately Alzheimer’s. Doses administered ranged from placebo to 10 milligrams per kilogram. The results were dramatic, in spite of the fact that patients were only mildly affected by Alzheimer’s. The outcomes proved that Aducanumab can be used to trick the body’s immune system into scrubbing away amyloid deposits. It is assumed that microglia cells were activated by the antibody, taking on the job of clearing away the deposits of amyloid. The degree of amyloid removal corresponded to dosage, with those who received the highest dose of 10 mg, resulting in amyloid scans as clean as those who were previously identified as having no amyloid deposits at all. Yet, at the same time, subjects who received the highest dosage also suffered the highest rate of side effects.
Adverse Effects Were Manageable
Overall, adverse events were considered to be manageable, at least within the context of a clinical trial. Subjects who received 10 mg experienced the highest adverse rate of 38%, which in clinical practice would present challenges for patient managers. But, the adverse rate dropped to 15% and below for the lower doses, and only 10% had to be removed from the trial due to adverse effects. This rate is similar to other therapies that have already been approved. Amyloid related imaging abnormalities (ARIA) was in this study as in other immune therapies for Alzheimer’s. Hi rates of ARIA were noted particularly in the high dose and genetically predisposed groups. Nevertheless, none of the subjects needed to be hospitalized. However, there is general consensus that in clinical practice, MRIs would be needed to watch out for ARIA, which is a potentially very serious complication. There was some cognitive decline observed in all groups which was also related to dosage. As would be expected, the group receiving the placebo showed the most cognitive decline, under two CDR-SB points. Those receiving the highest dose experienced cognitive decline of a little over .05 points. Improvement in rates of cognitive decline have been seen with other treatments aimed at reducing amyloid such as nilvadipine, a therapy under development by Archer. Nilvadipine is currently in phase 3 trials in 23 different sites around Europe. Nilvadipine is administered orally, once a day, whereas Aducanumab will need to be administered intravenously once a month.
Alzheimer’s Prevention Seems Possible
Overall, the results of the Biogen trial are very encouraging. Scientists have proven that fibrillar and amyloid oligomers can be removed, resulting in a measurable reduction of cognitive decline. We can look forward to the near future when therapeutic technologies such as Aducanumab can be a tool preventing Alzheimer’s disease from developing.
Early Alzheimer's Detection Through Non-Invasive Methods
A team of engineers and scientists from Northwestern University have come up with a unique way to detect Alzheimer's in living animals. Using non-invasive MRI, the team is able to detect signs at early stages before actual symptoms begin to appear.
The interdisciplinary team produced an MRI probe which links a magnetic nanostructure to an antibody that locates toxins called amyloid beta brain toxins, which are the cause of Alzheimer's onset. Proteins show up in the MRI scans as the dark areas in the brain due to their bond with magnetic nanostructures. This method of detecting molecular toxins could permit researchers to detect early onset, and although this was not the intended direction of the study, the results were fascinating. This molecular probe facilitated increased memory by bonding the toxins to block them from doing any more damage. Using the MRI, future researchers can observe toxins paired with neurons present in the brain and design ways to treat and eliminate toxins, ultimately improving the health of sufferers of the disease.
The new technology diverges from conventional methods of detection by identifying toxic amyloid beta oligomers rather than plaques that occur later in Alzheimer's development. It's widely accepted that these beta oligomers are responsible for the onset of Alzheimer's disease and related memory loss.
Mobile amyloid beta oligomers are responsible for destroying memory and ultimately neuron death through their attacks on the synapses of neurons. Over time the amyloid beta oligomers grow and begin to stick together, and this forms amyloid plaques, which current probes locate. Being able to accurately identify oligomers, which can reside in the brain for a decade before plaques can be detected, is groundbreaking for two key reasons: their toxins are responsible for damaging the neurons, and these molecular complexes are the earliest sign for the start of Alzheimer's disease.
Scans of Brain Injury Subjects Reveal Critical Information
Can your brain be older than you are?
In a healthy individual, free of disease or trauma, the concept is definitely out of the norm. But researchers at the Imperial College of London found that the brains of patients who have suffered severe head trauma aged by as much as five years or more depending upon the degree of trauma. Brain structure changes following the injury were very similar to what happens to brain matter as a person ages. The findings released in the journal Annals of Neurology are important to understanding the dynamic of brain structure change following traumatic brain injury and the potential for further deterioration as life progresses. The finding also may hold some keys for predicting a patient’s risk of developing Alzheimer’s disease.
Developing a model for scanning the brain
Scientists developed a new algorithm to produce an accurate computerized program that can predict the individual’s age from a reading of the scan. The algorithm observes the gray and white matter in the brain and notes important differences in volume. 1,500 individuals free of health issues were utilized to create the computer program. Scientists then scanned the brains of 99 patients who had experienced severe brain injuries and 113 who had not. From this pool came the startling results that the brain ages beyond the chronological aging, sometimes significantly, post brain trauma. The higher the number of years between the subject’s accident and their scan, the greater the difference between their chronological age and their brain age. This latter discovery confirmed for researchers that a traumatic brain injury is not just a one-time event, but rather that the changes in the brain due to the injury continue for years, with an increased risk of developing neurological disorders, such as Alzheimer’s.
The ramifications of the study are important to evaluating the accuracy of prediction models that will determine if abnormally older brains are a precursor to neurological degeneration down the road.
Alzheimer's And Brain Health
Alzheimer's is a debilitating disease that affects the brain. In 1909, German physician, Dr Alois Alzheimer first described it. His work on the disease was spurred by his interest in a mental health patient who experienced severe memory loss. Dr Alzheimer began studying the reasons for the degeneration of brain tissue and found that amyloid plaques and neurofibrillary tangles were responsible. Study of this disease was made possible when Ernst Ruska and Max Knoll invented the electron microscope in 1931. Various cognitive measurement scales were developed by 1963 and Congress decided on the establishment of a National Institute on Aging (NIA) in 1974. The NIA forms part of the National Institute of Health, and is a Federally funded research agency for Alzheimer's disease.
In 1976, a leading neurologist named Dr Katzman singled Alzheimer's as the most common cause of dementia. Barely a few years later, Jerome H. Stone held meetings with the NIA to create the Alzheimer's Association in 1980. Increased public awareness of the disease culminated in the establishment of National Alzheimer's Disease Month in November 1983. The following year, the National Institute on Aging presented findings of a Beta-amyloid that is perceived to be a cause of nerve cell damage. In healthy people, the neurons of cells do not contain neurofibrillary tangles, and there are no amyloid plaques visible. This is not the case with Alzheimer's sufferers.
These neurofibrillary tangles are thought to be caused by a protein known as Tau. This is a result of disintegrating microtubules and tangled clumps of proteins. An interesting development took place in 1987 when a gene from an inherited form of Alzheimer's disease was identified. By 1993 the FDA endorsed Cognex for the treatment of Alzheimer's symptoms. A transgenic mouse model with pathology similar to Alzheimer's was announced in 1995. This laid the foundation for future mouse models of this disease. By 2003 the NIA began recruiting people for a National Alzheimer's Disease Genetic Study. In 2004, an imaging agent known as Pittsburgh Compound B led to a breakthrough in the detection of this disease. It attaches to those amyloid deposits and can be picked up with PET scans.
With progress well underway, an International Conference on Alzheimer's Disease became a yearly event in 2009. The following year, clinical trials with a database of Alzheimer's patients was established. Some 4,000 patients were included in the study. In 2010, Alzheimer's jumped into sixth position as a leading cause of death in the US. It is surpassed only by heart disease, cancer, chronic lung disease, stroke and accidents.
The Chronicles of Alzheimer’s
Alzheimer’s is a progressively debilitating disease of the brain, which was first described in 1909 by the renowned German physician, Dr. Aloysius Alzheimer. After presenting the first case of presenile dementia, Alzheimer’s work later gave rise to the study of neurofibrillary tangles and amyloid plaques. This was facilitated by the invention of the electron microscope in 1931. Following advances in the development of cognitive measurement skills in 1963, work began on establishing a National Institute on Aging. The NIH was founded in 1974, and is today but one of 27 institutes devoted to researching and understanding the aging process, including the well-being of adults.
Dementia is a disorder affecting a person's mental processes, brought on by brain disease or injury. By 1976 Alzheimer's was officially recognized as the number one form of dementia by famed neurologist, Dr. Robert Katzman. This gave rise to the founding of the Alzheimer's Association in 1980 with Mr Jerome Stone as its president. As American awareness of Alzheimer's disease increased, Congress decided to declare November 1983 as National Alzheimer's Disease Month. By 1984, researchers found that Alzheimer's patients had neurofibrillary tangles and beta amyloid plaques. These are chief suspects in causing nerve cell damage in the brain.
In 1986, researchers discovered that one of the key components of tangles is a Tau protein. The diseased neurons in Alzheimer’s sufferers are comprised of tangled clumps of Tau proteins and disintegrating microtubules. One year later, the first Alzheimer's drug trial was conducted with tacrine. Also in the same year the first deterministic Alzheimer's gene for a rare form of the disease was found on Chromosome 21. The Food and Drug Administration (FDA) approved the first Alzheimer's drug in 1993 – tacrine - to target thinking symptoms and Alzheimer's memory. In 1995, researchers announced the first transgenic mouse model which developed brain pathology similar to Alzheimer's. In 2003, the National Alzheimer's Disease Genetics Study kicked off in earnest. And a year later, the Alzheimer's disease neuroimaging initiative brought together private donors and public donors with the purposes of establishing standards for the interpretation of brain images. These were presented in the form of PiB Pet Scans.
The International Conference on Alzheimer's Disease was officially inducted as an annual event in 2009 and efforts began in earnest to standardize biomarkers. One year later, in 2010, the Alzheimer's Association teamed up with the Coalition Against Major Diseases with a large database of patients that participated in clinical trials of Alzheimer's treatment regimens. In 2010 Alzheimer's disease became the sixth leading cause of death in the US, ahead of diabetes and just behind accidents. In 2010, the number of people who died as a result of Alzheimer's exceeded 500,000.
Researchers Find Zinc to be key Regulator of Apoptosis
A recent study published in the International Edition of Angewandte Chemie by researchers at Virginia Commonwealth University discusses the role of zinc in regulating apoptsis.
Apoptsis, or cell death, is necessary to healthy physical development. Certain enzymes regulate the process of apoptsis, keeping the body healthy. When there is a malfunction in the regulatory system, diseases such as cancers, and neurological disorders, such as Alzheimer’s and Parkinsons occur.
The researchers focused their efforts on caspase-3 which is known to be a major regulator of apoptsis. Zinc, which is a chief element in the human metabolic process, constrains the activity of caspases, which current drug treatments target to treat Alzheimers and other diseases. These findings are crucial to researchers’ efforts to develop new drug therapies that would target the interaction between zinc and caspase, and thereby regulate apoptsis.
Virginia Commonwealth University researchers utilized established investigative techniques, plus leading-edge computational practices to establish an undiscovered interaction site with caspase-3. Out of a total of 11 caspases known to researchers, seven are impacting apoptsis. Their study suggests that zinc may be regulating all caspases. Dr. Nicholas P. Farrell who is a member of the University’s Developmental Therapeutics program, acknowledges that more research is needed to establish if in fact all caspases are interacting with zinc, but the findings released provide an exciting foundation for inquiries into new drug therapies to treat neurological diseases.
Dr. Farrell adds that the new research findings is opening up a new protocol of discovery that scientists are calling the understanding of bioinorganic chemistry of apoptosis, or comprehending how essential metals, such as zinc, impact such vital processes as cell death. In fact, of interest, is that copper, which is aligned with zinc, has the opposite effect on apoptosis—it increases it.
Dec 10, 2012 Michael Mullan
New publication has provided us with recent developments in Star Scientific’s latest research relating to anatabine. Published in the European Journal of Pharmacology, the ingredient Anatabine, a minor alkaloid which is present in cigarette smoke and tobacco, has been shown to affect activity by Monoamine Oxidase (MAO), which is considered to be accountable for psychiatric and neurological chaos when dysfunctional. Following the use of the tobacco, Anatabine is absorbed by the human body and studies instigated by researchers at the Roskamp Institute and Star Scientific have established that anatabine succeeds at curbing brain inflammation in animal forms of Alzheimer`s disease.
Michael Mullan presentation at Neuroscience 2012: Anatabine Supplementation has been found to have positive influence in animal model of MS
Oct 16, 2012
Recent reports of the Roskamp Institute’s current research results have showed that the active ingredient in the dietary supplement Anatabloc®, Anatabine as a supplement, reduces inflammation significantly and neurological damage in an animal form of multiple sclerosis (MS). The findings which are a section of a sequence of data by researchers from the Roskamp Institute were publicized at the impressive scientific meeting in Louisiana, Neuroscience 2012, which is dedicated to brain and neurological science. First round results were originally reported on the Institute’s website but data had not been exposed before at an international scientific conference of this level.
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A Different approach is needed in Alzheimer’s research
by Michael Mullan
sep 19, 2012
With the failure of two recent clinical trials in the attempt to find treatment for Alzheimer’s disease, hope has unfortunately had to take a back seat. Treatment using the bapineuzumab vaccine was tried by Elan/Pfizer/Johnson & Johnson and the human antibody solazezumab, was tried by Eli Lilly. Both vaccines failed in producing an effect which physicians would consider extremely helpful although Eli Lilly’s results were more encouraging but full details have not yet been revealed so actual clarification has not yet been provided. Michael Mullan believes, as well as other experts in the field, that the Amyloid itself must be targeted before it deposits itself in the brain.
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Local study in on-going battle against dementia
by Michael Mullan
July 27, 2012
The Roskamp Institute is all set for its first major human trial of Anatabine, an anticipated treatment in Alzheimer's that makes use of a natural substance found in eggplants and tobacco leaves. This tobacco-leaf "nutraceutical" being tested, reduces inflammation and qualifies as a dietary supplement which does not require a drug approval. The Sarasota research center which specializes in neurological disorders, led by Michael Mullan, stresses that safety studies on the compound in humans have been carried out and are ready to study its effects on 200 individuals with mild to moderate dementia. In mice that were bred especially to have the degenerative brain disease, the formulation reduced inflammation and increased memory.
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Is Alzheimer’s at an End?
With Alzheimer’s disease becoming the 6th leading cause of death in Americans, researchers are keen to find a cure and the research center focused on this brain disease have recently begun performance in Europe of clinical trials on a drug that could well see the end of this cruel disease. With funding from a European Commission program, the $10 million trials will study the effect of Nilvadipine in over 500 patients diagnosed with Alzheimer’s. Scientists from the Roskamp Institute research center are convinced that the drug will have the same effect on humans as it does on mice, whereby symptoms have been slowed down or even reversed after taking Nilvadipine.
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Roskamp Institute’s works mainly on the research of Alzheimer’s
March 1st, 2012
Sarasota's Roskamp Institute is a world leader in the study of ways in the global war on Alzheimer’s disease. The research team which is headed by Michael Mullan, the institute’s CEO, has succeeded in the development of a new drug with potential to modify the course of this destructive disease. In finding ways to prevent the onset of this degenerative disease or ease the symptoms, a European research team consisting of nine countries recently launched phase III clinical trials to estimate effectiveness of Nilvadipine in over 500 patients with Alzheimer’s. This is a massive achievement by such a small research center in the scientific effort to conquer this disease.
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Already here: the Jackson Laboratory Model
The Roskamp Institute team, comprising of 50 experts and $30 million of equipment, are working on identifying the presence of proteins that experts hope to use in the treatment of Alzheimer’s disease. The Institute’s director Dr Michael Mullan estimates that around 150,000 square feet of space is required in order to accommodate future growth, putting them in parallel to the Jackson Laboratory which focuses on mammalian genetics research, investigation of cancer and other genetic illnesses. The Institute are working against the clock in the development of Nilvadipine and plans are going ahead to renovate a wing at the Institute into a small drug manufacturing facility for production of the active ingredient.
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More financial backing saught at Roskamp Institute
Roskamp Institute was originally founded by ex Physics teacher, Bob Roskamp, whose dream was to expand, research and find a cure for cognitive diseases, after losing his own brother to schizophrenia. Roskamp himself has been an evident philanthropist in Sarasota but is still working to secure funds from venture capitalists and drug companies in order to test the drug he believes is the cure for Alzheimer’s disease. Roskamp is trying to convince other humanitarians who have accumulated more funds than they actually require, to invest in his cause and help support the $5 million-plus budget and the skilled team of more than 50 scientists working at the Institute.
Michael Mullan tells Anna scott about plans to find cure
Advances in alzheimer's research - Local Scientist reveals work done
The origin of Alzheimer’s disease is still unclear but researchers at Roskamp Institute are aware that it stems from the accumulation of Amyloid, the protein that causes inflammation eliminating brain cells. Researchers have discovered a way of chemically blocking a part of the nerve cells that may reduce production of the protein linked to this progressive form of dementia. They found that a receptor on nerve cells is where the Amyloid-creating reaction occurs and by interfering with this site, then Amyloid production is interrupted. Clinical trials are being carried out at Roskamp of a drug shown to lower levels of Amyloid, and a large number of different drugs are also at different development stages.
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New Drug testing for Alzheimer's
In early 2008 Dr Michael Mullan, researcher and director of the Roskamp Institute in Florida told an assembly at the Pines of Sarasota long-term care center that hope was on the horizon for sufferers of Alzheimer's disease and that the drug that the institute was testing at that time was ready to enter clinical trials stage. The institute was examining a few options but its most likely candidate was Nilvadipine which had been approved in Japan and Europe and was used extensively in the treatment of hypertension in those countries. The drug was also found to increase blood flow and reduce levels of the protein believed to be the primary cause of Alzheimer’s disease.
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