Posts tagged brain diseases
Articles and news from the latest research reports.
New knowledge about the brain’s effective bouncer
Research from the University of Copenhagen is shedding new light on the brain’s complicated barrier tissue. The blood-brain barrier is an effective barrier which protects the brain, but which at the same time makes it difficult to treat diseases such as Alzheimer’s. In an in vitro blood-brain barrier, researchers can recreate the brain’s transport processes for the benefit of the development of new pharmaceuticals for the brain. The new research findings are published in the AAPS Journal.
Ninety-five per cent of all tested pharmacological agents for treating brain disorders fail, because they cannot cross the blood-brain barrier. It is therefore important to find a possible method for transporting drugs past the brain’s efficient outpost and fervent protector.
Researchers at the Department of Pharmacy at the University of Copenhagen have recreated the complex blood-brain barrier in a laboratory model, which is based on cells from animals. In a new study, the researchers have studied the obstreperous bouncer proteins in the barrier tissue. The proteins protect the brain, but also prevent the treatment of brain diseases:
"The blood-brain barrier is chemically tight because the cells contain transporter proteins which make sure that substances entering the cells are thrown straight back out into the bloodstream again. We have shown that the barrier which we have created in the laboratory contains the same bouncer proteins – and that they behave in the same way as in a ‘real’ brain. This is important, because the model can be used to test drive the difficult way into the brain. Complex phenomena – which we have so far only been able to study in live animals –can now be investigated in simple laboratory experiments using cultivated cells," says postdoc Hans Christian Cederberg Helms from the Department of Pharmacy.
The research team has shown that the transporter proteins P-glycoprotein, breast cancer resistance protein and multidrug resistance-associated protein 1 are active in the artificially created barrier tissue. The proteins pump pharmacological agents from the ‘brain side’ to the ‘blood side’ in the same way as in the human blood-brain barrier.
Collaboration finds a way
The new findings have resulted from collaboration with industrial scientists from the pharmaceutical company H. Lundbeck A/S. “It is important to the treatment of brain diseases such as Alzheimer’s that we find a way of circumventing the brain’s effective defence. The university and industry must work together to overcome the fundamental challenges inherent in developing pharmaceuticals for the future,” says Lassina Badolo, Principal Scientist with H. Lundbeck A/S and an expert on the absorption of medicines in the body.
Associate Professor Birger Brodin adds: “We have shown that the models have the same bouncer proteins as the ones found in the intact barrier. We are now in the process of studying the proteins in the blood-brain barrier that accept pharmacological agents instead of throwing them out. If we can combine a beneficial substance which the brain needs with a so-called ‘absorber protein’, we will in the long term be able to smuggle pharmacological agents across the blood-brain barrier.”
Birger Brodin heads the Drug Transporters in ADME research group which is responsible for the in vitro blood-brain barrier.
(Source: healthsciences.ku.dk)
Breakthrough: Nasal spray may soon replace the pill
When the doctor gives us medicine, it is often in the shape of a pill. But when it comes to brain diseases, pills are actually an extremely ineffecient way to deliver drugs to the brain, and according to researchers from University of Southern Denmark we need to find new and more efficient ways of transporting drugs to the brain. Spraying the patient’s nose could be one such way.
Every time we have an infection or a headache and take a pill, we get a lot more drugs than our body actually needs. The reason is that only a fraction of the drugs in a pill reaches the right places in the body; the rest never reaches its destination and may cause unwelcome side effects before they are flushed out of the body again. This kind of major overdosing is especially true when doctors treat brain diseases, because the brain does not easily accept entering drugs.
"People with brain diseases are often given huge amounts of unnecessary drugs. During a long life, or if you have a chronic disease, this may become problematic for your health", says Massimiliano Di Cagno, assistant professor at the Department of Physics, Chemistry and Pharmacy, University of Southern Denmark.
He is concerned with finding more efficient ways of delivering drugs to the brain. He and his colleagues at University of Southern Denmark and Aalborg University have turned their attention to the nose - specifically the nasal wall and the slimy mucosa that covers it.
As we know from e.g. cocaine addicts, substances can be assimilated extremely quickly and directly through the nose. But many medical substances, however, need help to be transported through the nasal wall and further on to the relevant places in the brain.
Researchers have long struggled with this challenge and have come up with different kinds of transport vehicles that are very good at transporting the active ingredients through the nasal wall into the brain. The problem with these vehicles, though, is that they cannot release their cargo of drugs once they have reached the inside of the brain. The drugs stay locked inside the strong vehicles.
“If the drugs cannot get out of their vehicles, they are no help to the patient. So we needed to develop a vehicle that does not lock the drug in”, explains Massimiliano Di Cagno.
The vehicles for drug delivery through the nose are typically made of so called polymers. A polymer is a large molecule composed of a large number of repeats of one or more types of atoms or groups of atoms bound to each other. Polymers can be natural or synthetic, simple or complex.
Direct track to the brain
Massimiliano Di Cagno and his colleagues tested a natural sugar polymer and they now report that this particular polymer is not only capable of carrying the drugs through the nasal wall but also – and most importantly – releasing the drug where it is needed.
"This is an important breakthrough, which will bring us closer to delivering brain drugs by nasal spray", says Massimiliano Di Cagno.
With this discovery two out of three major challenges in nasal delivery of brain drugs have been met:
“We have solved the problem of getting the drug through the nose, and we have solved the problem of getting the drug released once it has entered the brain. Now there is a third major challenge left: To secure a steady supply of drugs over a long period. This is especially important if you are a chronic patient and need drug delivery every hour or so”, says Massimiliano Di Cagno.
When a patient sprays a solution with active drugs into his nose cavity, the solution will hit the nasal wall and wander from here through the nasal wall to the relevant places in the brain.
“But gravity also rules inside the nose cavity and therefore the spray solution will start to run down as soon as it has been sprayed up the nose. We need it to cling to the nasal wall for a long time, so we need to invent some kind of glue that will help the solution stick to the nasal wall and not run down and out of the nose within minutes”, says Massimiliano Di Cagno.
Thinking it through: Scientists seek to unlock mysteries of the brain
Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to this challenge, we will gain profound insights into what makes us human, develop new treatments for brain diseases, and build revolutionary new computing technologies that will have far reaching effects, not only in neuroscience.
Scientists at the European Human Brain Project—set to announce more than a dozen new research partnerships worth Eur 8.3 million in funding later this month—the Allen Institute for Brain Science, and the US BRAIN Initiative are developing new paradigms for understanding how the human brain works in health and disease. Today, their international and collaborative projects are defined, explored, and compared during “Inventing New Ways to Understand the Human Brain,” at the 2014 AAAS Annual Meeting in Chicago.
Brain Simulation, Big Data, and a New Computing Paradigm
Henry Markram from the Ecole Polytechnique Fédérale de Lausanne (EPFL), in Switzerland, where the Human Brain Project is based, describes how the project will leverage available experimental data and basic principles of brain organization to reconstruct the detailed structure of the brain in computer models. The models will allow the HBP to run super-computer based simulations of the inner working of the brain.
"Brain simulation allows measurements and manipulations impossible in the lab, opening the road to a new kind of in silico experimentation," Markram says.
The data deluge in neuroscience is resulting in a revolutionary amount of brain data with new initiatives planning to acquire even more. But searching, accessing, and analyzing this data remains a key challenge.
Sean Hill, also of EPFL and a speaker at AAAS, leads The Neuroinformatics Platform of the Human Brain Project (HBP). In this scientific panel, he explains how the platform will provide tools to manage, navigate, and annotate spatially referenced brain atlases, which will form the basis for the HBP’s modeling effort—turning Big Data into deep knowledge.
The Neuroinformatics Platform will bring together many different kinds of data. University of Edinburgh’s Seth Grant, a key member of the HBP, describes how he is deriving new methods to decode the molecular principles underlying the brain’s organization, such as how individual proteins assemble into larger complexes. As Grant explains in Chicago, this has important practical applications as many mutations in schizophrenia and autism converge on these so-called supercomplexes in the brain.
As we understand more and more about the way the brain computes we can apply this knowledge to technology. Karlheinz Meier, of Heidelberg University in Germany and a speaker at AAAS, outlines how he is working to create entirely new computing systems as part of the HBP. These Neuromorphic Computing Systems will merge realistic brain models with new hardware for a completely new paradigm of computing—one that more closely resembles how the brain itself processes information.
"The brain has the ability to efficiently perform computations that are impossible even for the most powerful computers while consuming only 30 Watts of power," Meier says.
Brain: Get Ready For Your Close-up
At AAAS, Christof Koch lays out another ambitious, 10-year plan from the Allen Institute for Brain Science: to understand the structure and function of the brain by mapping cell types from mice and humans with computer simulations and figuring out how the cells connect, and how they encode, relay, and process information. The project, Koch says, promises massive, multimodal, and open-access datasets and methodology that will be reproducible and scalable.
At Harvard University, George Church is participating in the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which aims to map every neuron in the brain with rapidly advancing technologies. At AAAS, he describes progress on new tools for measurements of brain cell development, connectivity, and functional state dynamics in rodent and human clinical samples.
What do all of these projects have in common? They seek to help find some of the most elusive answers known to man: what makes us human, how does the brain function, what causes neurological and mental illness, and, most importantly, how can we treat or cure these afflictions?
Brain diseases affecting more people and starting earlier than ever before
Professor Colin Pritchard’s latest research published in Public Health Journal has found that the sharp rise of dementia and other neurological deaths in people under 74 cannot be put down to the fact that we are living longer – the rise is because a higher proportion of old people are being affected by such conditions, and what is really alarming, it is starting earlier and affecting people under 55 years.
Of the 10 biggest Western countries the USA had the worst increase in all neurological deaths, men up 66% and women 92% between 1979-2010. The UK was 4th highest, men up 32% and women 48%. In terms of numbers of deaths, in the UK, it was 4,500 and now 6,500, in the USA it was 14,500 now more than 28,500 deaths!
Professor Pritchard of Bournemouth University says: “These statistics are about real people and families, and we need to recognise that there is an ‘epidemic’ that clearly is influenced by environmental and societal changes.”
Tessa Gutteridge, Director YoungDementia UK says that our society needs to learn that dementia is increasingly affecting people from an earlier age: “The lives of an increasing number of families struggling with working-age dementia are made so much more challenging by services which fail to keep pace with their needs and a society which believes dementia to be an illness of old age.”
Bournemouth University researchers, Professor Colin Pritchard and Dr Andrew Mayers, along with the University of Southampton’s Professor David Baldwin show that there are rises in total neurological deaths, including the dementias, which are starting earlier, impacting upon patients, their families and health and social care services, exemplified by an 85% increase in UK Motor Neurone Disease deaths.
The research highlights that there is an alarming ‘hidden epidemic’ of rises in neurological deaths between 1979-2010 of adults (under 74) in Western countries, especially the UK.
Total neurological deaths in both men and women rose significantly in 16 of the countries covered by the research, which is in sharp contrast to the major reductions in deaths from all other causes.
Over the period the UK has the third biggest neurological increase, up 32% in men and 48% in women, whilst women’s neurological deaths rose faster than men’s in most countries.
Professor Pritchard said, “These rises in neurological deaths, with the earlier onset of the dementias, are devastating for families and pose a considerable public health problem. It is NOT that we have more old people but rather more old people have more brain disease than ever before, including Alzheimer’s. For example there are two new British charities, The Young Parkinson’s Society and Young Dementia UK, which are a grass-roots response to these rises. The need for such charities would have been inconceivable a little more than 30 years ago.”
When asked what he thought caused the increases he replied,
“This has to be speculative but it cannot be genetic because the period is too short. Whilst there will be some influence of more elderly people, it does not account for the earlier onset; the differences between countries nor the fact that more women have been affected, as their lives have changed more than men’s over the period, all indicates multiple environmental factors. Considering the changes over the last 30 years – the explosion in electronic devices, rises in background non-ionising radiation- PC’s, micro waves, TV’s, mobile phones; road and air transport up four-fold increasing background petro-chemical pollution; chemical additives to food etc. There is no one factor rather the likely interaction between all these environmental triggers, reflecting changes in other conditions. For example, whilst cancer deaths are down substantially, cancer incidence continues to rise; levels of asthma are un-precedented; the fall in male sperm counts - the rise of auto-immune diseases - all point to life-style and environmental influences. These `statistics’ are about real people and families, and we need to recognise that there is an `epidemic’ that clearly is influenced by environmental and societal changes.”
Australian scientists map mouse brains in greatest detail yet
Hopes for a cure for many brain diseases may rest on the humble mouse, now that scientists can map the rodents’ brains more thoroughly than ever before.
Researchers at The University of Queensland’s Centre for Advanced Imaging (CAI) and Curtin University have created the most detailed atlas of the mouse brain, a development that is helping in the fight against brain disease.
This new tool will allow researchers to map what parts of the brain are affected in mouse models of brain disease – such as brain cancer, Parkinson’s disease and Alzheimers disease, which affect nearly 1 in 6 of the world’s population.
Lead author, Dr Jeremy Ullmann said that the new brain atlas provided a fundamental tool for the neuroscience community.
“The mouse is now the most widely used animal model for neuroscience research and magnetic resonance imaging (MRI) is fundamental to investigating changes in the brain,” Dr Ullman said.
“Our atlas is already much in demand internationally because it allows researchers to use MRI to automatically map brain structures.”
The atlas was created in the laboratory of Professor David Reutens, CAI Director.
“In making these world-first maps, we had the advantage of using the most powerful MRI scanners in the Southern Hemisphere, backed up by leaders in digital image analysis, resulting in remarkably clear images of the brain,” Professor Reutens said.
The project’s lead neuroanatomist, Professor Charles Watson from Curtin University, believes that the study will open the door to accurate analysis of gene targeting in the mouse brain.
“The invention of gene targeting in the mouse has made this species the centrepiece of studies on models of human brain disease. MRI allows researchers to follow changes in the brain over time in the same animals,” Professor Watson said.
The atlas was recently described in an article published in the journal NeuroImage.
New research findings on the brain’s guardian cells
Researcher Johan Jakobsson and his colleagues have now published their results in Nature Communications.
At present, researchers know very little about exactly how microglia work. At the same time, there is a lot of curiosity and high hopes among brain researchers that greater understanding of microglia could lead to entirely new drug development strategies for various brain diseases”, says Johan Jakobsson, research group leader at the Division of Molecular Neurogenetics at Lund University.
What the researchers have now succeeded in identifying is a deviation in the structure of the microglia cells, which makes it possible to visualise them and study their behaviour. By inserting a luminescent protein controlled by a microscopic molecule, microRNA-9, the researchers can now distinguish the microglia and monitor their function over time in the brains of rats and mice.
It has long been known that microglia form the first line of defence of the immune system in diseases of the brain. They move quickly to the affected area and release an arsenal of molecules that protect the nerve cells and clear away damaged tissue.
New research also suggests that microglia not only guard the nerve cells but also play an important role in their basic function.
“This represents a real step forward in technological development. Now we can view microglia in a way that has not been possible before. We and our colleagues now hope to be able to use this technique to study the role of the cells in different disease models, for example Parkinson’s disease and stroke, in which microglia are believed to play an important role”, explains Johan Jakobsson.
Watch it to Believe it. http://www.humanbrainproject.eu/
Full 10 Year Joint EU funding (2013-2023) with over 1 Billion Euro`s has now started!!!
Human brain research made easier by database
Researchers will be able to access samples from more than 7,000 donated human brains to help study major brain diseases, thanks to a new on-line database, launched by the Medical Research Council (MRC) today.
The UK Brain Banks Network database speeds up access to donated brain samples held across 10 brain banks in the UK and allows researchers studying Multiple Sclerosis, Alzheimer’s, Parkinson’s and a range of other neurodegenerative and developmental diseases to track down human tissue samples for their work.
Thanks to a unique collaboration between the MRC and five leading charities, the database will help scientists from academia and industry investigate the underlying causes of major brain diseases and understand how they take hold in our bodies.
Although scientists can model diseases in the lab, to fully understand dementia and other brain-related disorders they need to study human brain tissue. A lot of research relies on donated brain tissue stored in brain banks across the UK. Until today, researchers had to apply to each brain bank in turn to find out if they held the samples they needed and find the ‘control’ samples (donated brains free from disease) for comparison – a long and drawn out process. Now samples can be found with the click of a button from one source.
Professor James Ironside, Director of the MRC UK Brain Banks Network, said:
“The database is the result of four years of painstaking planning and data analysis by very dedicated people. It will enable quick and easy access for researchers who are already working on neurological or psychiatric disease (perhaps in animal models or cells) and would like to translate their findings into human tissue and is very useful for those who are planning a grant application. The brain banks have already been given ethical approval, cutting out the need for researchers to go through a separate ethics application.
We must remember that vital research would not be possible without the generosity of those individuals who donate their brains to medical research. We’re working hard to make sure that the access for researchers studying brain samples is much easier. The next step is to improve the systems for those wishing to donate their brain to medical research.”
Five leading charities helped to supply data for the database; the MS Society, Parkinson’s UK, Alzheimer’s Society, Alzheimer’s Research UK and Autistica.
For more information about the database visit: http://www.mrc.ac.uk/brainbanksnetwork