Alzheimer’s Drugs Linked to a Reduced Risk of Heart Attacks

The European Heart Journal, an online publication, looked at a study from Sweden involving Alzheimer’s medication and heart attacks.  The research, which had a testing base of 7,000 people with Alzheimer’s disease, showed that drugs typically administered in the early stages of Alzheimer’s reduced patient risk of heart attack and death by any means.

The study looked at cholinesterase inhibitors (ChEIs), including donepezil, rivastigmine, and galantamine, which aid in the treatment of moderate Alzheimer’s disease.  Scientists became interested in the possible effect of this drug on the heart because it is targeted at reducing the chronic inflammation seen in Alzheimer’s patients, and a side effect of ChEls is the calming of the vagus nerve, which is responsible for controlling the heartbeat.  At Umea University in Sweden, Professor Peter Nordstrom and his colleagues followed 7,073 people with Alzheimer’s disease who appeared on the Swedish Dementia Registry for an average of two years. They found that those individuals who were on ChEIs had a 36 percent reduced risk of death in general, a 38 percent reduced risk of a myocardial infarction (heart-attack), and a 26 percent reduction in the risk of any cardiovascular-related death, such as stroke, compared to those not on the ChEIs. Professor Nordstrom remarked the results if translated into absolute figures representing the data of one year for a group of 100,000 individuals with Alzheimer’s disease on ChEls; there would be 180 fewer heart attacks (295 compared to 475), and 1,125 fewer deaths overall (2000 cases versus 3,125).  It was also recorded that patients who took the highest levels possible of ChEIs while remaining safe had a 65% lower risk of heart attack and a 46 % lower risk of death than those who did not take the anti-inflammatory.  As a control, scientists tested other types of medication commonly administered to Alzheimer’s and dementia patients, and the research found no change or significant results. The study holds scientific uncertainty, for while it yields promising data, the scientists cannot say that ChEls are responsible for the lowering the risks, only that is in some way related to said reduction.  However, the strong results hold promise, and Professor Nordstrom said that further experimentation and trials involving the anti-inflammatory drug could bring forth more information regarding its role in the reduction of risk of myocardial infarction and death.

1) P. Nordstrom, D. Religa, A. Wimo, B. Winblad, M. Eriksdotter. The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer’s disease. European Heart Journal, 2013; DOI: 10.1093/eurheartj/eht182

2) European Society of Cardiology (ESC) (2013, June 5). Alzheimer’s disease drugs linked to reduced risk of heart attacks. ScienceDaily. Retrieved June 7, 2013, from http://www.sciencedaily.com/releases/2013/06/130605090257.htm

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

The Parkin Protein and Disease Mutations

From the MRC Laboratory of Molecular Biology in the United Kingdom comes research that has determined the crystal structure of Parkin, a protein linked to Parkinson’s disease.  Results published in The EMBO Journal better define the positioning of many mutations that are linked to hereditary Parkinson’s disease.

Parkinson’s disease is a progressive neurodegenerative disease that occurs mostly in older individuals sporadically, or not hereditarily.  However, around 15% of patients develop symptoms early in life due to inherited mutations in a limited number of disease genes. These mutations are especially detrimental, causing more damage to nerve cells than non-mutated forms of Parkin.  Scientists believe this occurs because previous research has suggested the Parkin protein regulates energy production within cells.  For familial cases of inherited disease genes, around 50% are caused by mutations in the PARKIN gene that encodes a protein within the RBR ubiquitin ligase enzyme family. These mutated enzymes couple other proteins together within the cell to create a molecule called ubiquitin.  But since the enzymes catalyzing these reactions are mutated forms of the PARKIN gene, the critical ubiquitin proteins can be unstable or altered in their function.

EMBO investigator David Komander and his co-worker Tobias Wauer crystallized a form of human Parkin and used X-ray diffraction patterns to determine the way in which the protein chain folds into a three-dimensional structure. The experiments revealed the existence of an in-built control mechanism for Parkin activity, one that is lost in the presence of the mutations which cause Parkinson’s disease. Komander and Wauer pinpointed amino acids of Parkin that had key functions of ubiquitin ligase enzyme activity, and found that the proteins they create are sensitive to blocking by reagents that had already been categorized by their laboratory.  This means that after identifying building blocks of Parkin, the scientists blocked their ability to form larger, mutated, ubiquitin molecules.  The crystal structure of Parkin goes on to reveal secrets regarding the molecule, which scientists are hopeful may one day be used as a way to treat or slow the progression of Parkinson’s. There is reason to believe that other studies on crystal structure could lead scientists to find compounds that are capable of altering Parkin’s activity.

1) Tobias Wauer, David Komander. Structure of the human Parkin ligase domain in an autoinhibited state. The EMBO Journal, 2013; DOI: 10.1038/emboj.2013.125

2) EMBO – ecellence in life sciences (2013, May 31). How disease mutations affect the Parkin

protein. ScienceDaily. Retrieved June 3, 2013, from http://www.sciencedaily.com/releases/2013/05/

By: Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

Brain Function Affected by Change in Gut Bacteria

At ULCA, researchers conducted a study that tested women who regularly consumed yogurt containing beneficial bacteria called probiotics, to see if they had any alteration in brain function compared to women who did not consume the probiotics in yogurt. The study showed that the women who regularly ate yogurt had an alteration in both a resting state and emotional recognition brain function.

Researchers speculated that by changing the bacteria’s environment in the gut, brain functionality could be augmented. The study was small, consisting of only 36 healthy women of ages 18-55. The women were divided into three groups: one group was given yogurt with probiotics twice a day for four weeks, one group was given a look-alike yogurt with no probiotics, and the third group did not have any yogurt. Comparing MRI scans taken before and after the study, researchers found that women who consumed the probiotic yogurt saw a decrease in insula, which processes and integrates body sensations, as well as in the somatosensory cortex during emotional-recognition testing. These women also saw a decrease in widespread engagement of the brain to deal with emotion, cognition, and sensory-related tasks.  The women who did not eat the probiotic yogurt had increased levels of brain network activity, spread out across more area. Furthermore, during the resting brain scan, women consuming probiotics had a higher connectivity of the brainstem to cognition, while the women not eating any yogurt saw increase of emotional and sensational connection to the brainstem.  The women eating the look-alike yogurt fit between the two extremes.  Researchers were astounded to find the various effects on the brain due to consumption of probiotics, such as the change in sensations as well as processes of emotional responses. The linkage of signals between the intestines and the brain will lead scientists to explore new routes of research.  These innovative news possibilities include changes in diet to test for varying levels of brain response and functionality.

Sources:

1) Kirsten Tillisch, Jennifer Labus, Lisa Kilpatrick, Zhiguo Jiang, Jean Stains, Bahar Ebrat, Denis Guyonnet, Sophie Legrain-Raspaud, Beatrice Trotin, Bruce Naliboff, Emeran A. Mayer. Consumption of Fermented Milk Product with Probiotic Modulates Brain Activity. Gastroenterology, 2013; DOI: 10.1053/j.gastro.2013.02.043

2) University of California, Los Angeles (UCLA), Health Sciences (2013, May 28).

Changing gut bacteria through diet affects brain function. ScienceDaily. Retrieved May 29, 2013, from http://www.sciencedaily.com/releases/2013/05/130528180900.htm

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

Rats Injected with Stem Cells: Improved Spinal Injuries?

Researchers at the University of California, San Diego School of Medicine led a study in which rats were injected with one dose of human neural stem cells.  The cell graft improved function and mobility, as well as neuronal regeneration in the rats suffering from acute spinal cord injuries.

According to anesthesiology professor Dr. Martin Marsala and colleagues at the University of California, grafting neural stem cells derived from human fetal spinal cords, and transferring the cells to the rats spinal injury site had many therapeutic benefits.  These benefits range from less spasticity of muscles to the forging of new connections between the injected stem cells and surviving neurons within the rats. The scientists reported that the human stem cells seemed to take root vigorously at the injury site, aiding the recovery process to the point where any cavities or cysts formed at the injury site disappeared as grafted cells were introduced.

The rats received the stem cell injections exactly three days after sustaining the spinal injury, in addition to several drugs that lessened the immune response of the rats so that their bodies would properly accept the stem calls. The stem cells appeared to stimulate the rats’ neuron regeneration, as well as partially replace functionality of lost neurons. The rats had greater control of their paws, and a raised overall quality of life.

With this knowledge in hand, scientists are working to develop neural precursor cells that could potentially become any one of the three cell types found in the nervous system.  This would lead to induced pluripotent stem cells derived from patients, a tool that void the need of immunosuppressants in stem cell therapies.

Sources:

  • Sebastiaan van Gorp, Marjolein Leerink, Osamu Kakinohana, Oleksandr Platoshyn, Camila Santucci, Jan Galik, Elbert A Joosten, Marian Hruska-Plochan, Danielle Goldberg, Silvia Marsala, Karl Johe, Joseph D Ciacci, Martin Marsala. Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation. Stem Cell Research & Therapy, 2013; 4 (5): 57 DOI: 1186/scrt209
  • University of California – San Diego (2013, May 27). Stem cell injections improve spinal injuries in rats. ScienceDaily. Retrieved May 28, 2013, from http://www.sciencedaily.com­ /releases/2013/05/130527231843.htm

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

Alzheimer’s disease: Molecular Trigger Found?

Scientists at Cambridge’s Department of Chemistry have been able to construct a detailed map that shows how the formation of aberrant proteins in the brain can lead to a build-up so massive that it causes the development of numerous brain-damaging diseases, chief among them being Alzheimer’s.

In 2010, the Alzheimer’s Research Trust found that dementia alone cost the UK economy 23 billion euros, more than the costs of cancer and heart disease combined. Normally, proteins are made up of chemical building blocks known as amino acids, which are joined together in a code ordered by our DNA. New proteins appear as long, thin strips, which are then intricately folded to properly carry out their designated biological function. However, there are points at which the amyloid-beta protein misfolds or unfolds and gets tangled with other newly-made proteins. The tangles stick to one another until they number in the millions, known as amyloid fibrils, and they start the huge deposits of proteins known as plaque, which are so large, they become insoluble.

When the plaque in the brain reaches a critical level, a chain reaction is set off, and new focal points of tendrils form. From these tendrils, a smaller number of proteins, known as toxic oligomers, can easily diffuse through membranes, effectively killing neurons and causing memory loss as well as other dementia symptoms. This new groundbreaking information required scientists to come together, using kinetic experiments with a framework of theory. Master equations, more commonly used in the fields of chemistry and physics, aided researchers in their efforts to better understand Alzheimer’s, and how effectively to fight it.

 

Sources:

 

Source 1)

University of Cambridge (2013, May 20). Molecular trigger for Alzheimer’s disease identified. ScienceDaily. Retrieved May 22, 2013,

 

Source 2)

Samuel I. A. Cohen, Sara Linse, Leila M. Luheshi, Erik Hellstrand, Duncan A. White, Luke Rajah, Daniel E. Otzen, Michele Vendruscolo, Christopher M. Dobson, and Tuomas P. J. Knowles. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1218402110

 

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

Toxic Brain Protein: Stopped by Cancer Drug?

At Georgetown University Medical Center, tiny dosage amounts of a Leukemia-inhibiting drug known as nilotinib, were administered to lab mice in a clinical trial meant to examine the effects of the drug on inhibiting the formation of certain proteins in the brain.
These are the same types of proteins that cause accumulation of plaques and decreased cognition in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Lewy Body dementia. Dr. Charbel E-H Moussa, head of the dementia laboratory at Georgetown University, stated that when nilotinib is used to treat CML, it intentionally sends cells into auto-cannibalism, referred to medically as autophagy. The end game of administering this drug to Lukemia patients is the cannibalization of their organelles, and resultantly the death of tumor cells. Moussa’s study broke ground as the first series of experiements testing these types of medications on patients suffering various nueordegenerative disorders. The theory behind using nilotinib was that a small dosage would cause the cells to clean out stores of proteins, but not send them over the edge into a state of autophagy. Mice used in their lab over-expressed alpha-Synuclein, a protein linked to plaque aggregation, and were given one Milligram of nilotinib every two days. Testing of the drug concluded that nilotinib would clean out the toxic brain proteins by causing the cells to go into a state of controlled and partial autophagy , resulting in drastically heightened movement and functionality. At the end of the experiment, Moussa hypothesized that in order for therapy of these neurological diseases to be effective, it must developed and administered as soon as possible. Later usage may result in the retardation of extracellular formation, as well as the accumulation of intracellular proteins such as Lewy bodies, which job it was for nilotinib to remove in the first place.
Sources:
1) Michaeline L. Hebron, Irina Lonskaya, and Charbel E.-H. Moussa. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson’s disease models. Hum. Mol. Genet., May 10, 2013 DOI: 10.1093/hmg/ddt192
2) Georgetown University Medical Center (2013, May 10). Cancer drug prevents build-up of toxic brain protein. ScienceDaily. Retrieved May 22.

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

Key to Treating Alzheimer’s: Brain Garbage Truck?

Researchers at the University of Rochester Medical Center point to a newly discovered system, which processes and removes waste in the brain, as a possible key to treating neurological disorders such as Alzheimer’s disease.
Modern scientists are beginning to build on the late-1800s understanding of the “blood-brain barrier” with new incoming knowledge of the brain’s dynamics for removing waste, recently dubbed the glymphatic system. The lymphatic system, a circulatory network of organs and vessels, removes waste materials from the rest of the body, but does not extend to the brain. Scientists began to postulate about how the brain kept house, one of the main issues being that there is no trace of any such system within brain tissue samples. But new technology known as two-photon microscopy allowed scientists to delve deeper into the living brain for study. Coupling the new tech with mice brains, Dr. Maiken Nedergaard, co-director of the URMC for Transitional Medicine, and her colleagues were able to observe and document the extensive waste system of the brain.
The brain is surrounded by a membrane, called the arachnoid, that is flushed with cerebral spinal fluid (CSF) which flows through the brain on the same pathways as the arteries reaching the brain. CSF is drawn into the brain tissue through a system of conduits controlled by glia, support cells. CSF is moved through the brain at high speeds, picking up excess proteins and waste products along the way. The fluid and waste are channeled into a system which parallels veins and transports the byproducts from the brain, down the spinal column, and to the liver where everything is ultimately broken down. With this discovery, scientists can delve into the research regarding how to apply this knowledge in the treatment of neurological disorders. This find may prove especially beneficial in the case of Alzheimer’s, a disease whose hallmark is the build-up of beta amyloid plaques. Further research would test whether manipulating glia to ramp up waste removal would better prevent the build-up of excess proteins such as beta amyloid.
Source:
1) University of Rochester Medical Center (2013, June 27). Brain’s ‘garbage truck’ may hold key to treating Alzheimer’s and other disorders. ScienceDaily. Retrieved July 1, 2013, from http://www.sciencedaily.com/releases/2013/06/130627142402.htm

By Lauren Horne