Immunotherapy has proven to be effective against many serious diseases. But to treat diseases in the brain, the antibodies must first get past the obstacle of the blood-brain barrier. In a new study, a research group at Uppsala University describes their development of a new antibody design that increases brain uptake of antibodies almost 100-fold.
Immunotherapy entails treatment with antibodies; it is the fastest growing field in pharmaceutical development. In recent years, immunotherapy has successfully been used to treat cancer and rheumatoid arthritis, and the results of clinical studies look very promising for several other diseases. Antibodies are unique in that they can be modified to strongly bind to almost any disease-causing protein. In other words, major potential exists for new antibody-based medicines.
The problem with immunotherapy for diseases affecting the brain is that the brain is protected by a very tight layer of cells, called the blood-brain barrier. The blood-brain barrier effectively prevents large molecules, such as antibodies, from passing from the bloodstream into the brain. It has therefore been difficult to use immunotherapy to treat Alzheimer’s and Parkinson’s disease, which affect the brain, as well as cancerous tumours in the brain.
It has been known for a long time that some large proteins are actively transported across the blood-brain barrier. These include a protein called transferrin, whose primary task is to bind to iron in the blood and then transport it to the brain. The research group behind this new study has taken advantage of this process and modified the antibodies they want to transport into the brain using components that bind to the transferrin receptor. Then, like a Trojan horse, the receptor transports antibodies into the brain. The number of modifications to and placement of the antibodies have proven to be important factors for making this process as effective as possible.
“We’ve placed them so that each antibody only binds with one modification at a time, despite being modified in two places. Our design thus doubles the chances of the antibody binding to the transferrin receptor compared with only one modification. We’ve successfully increased the amount of antibodies in the brain almost 100-fold, which is the largest uptake improvement that has ever been shown,” says Greta Hultqvist, researcher at the Department of Public Health and Caring Sciences at Uppsala University.
To try out the new format, researchers have used it on an antibody that binds to a protein involved in the course of Alzheimer’s disease. Without the modification, they could only detect very small quantities of antibody in the brain in a mouse model of Alzheimer’s disease, while they could detect high levels of the modified antibody in the same mice.
“From a long-term perspective, it’s likely that the new format can be used to effectively treat not only Alzheimer’s disease, but also other diseases affecting the brain,” says Dag Sehlin, researcher at the Department of Public Health and Caring Sciences at Uppsala University.
It ranks among the best universities in Northern Europe in international rankings.
The university rose to pronounced significance during the rise of Sweden as a great power at the end of the 16th century and was then given a relative financial stability with the large donation of King Gustavus Adolphus in the early 17th century. Uppsala also has an important historical place in Swedish national culture, identity and for the Swedish establishment: in historiography, literature, politics, and music. Many aspects of Swedish academic culture in general, such as the white student cap, originated in Uppsala. It shares some peculiarities, such as the student nation system, with Lund University and the University of Helsinki.
Uppsala belongs to the Coimbra Group of European universities. The university has nine faculties distributed over three “disciplinary domains”. It has about 23,000 full-time students, and about 2,400 doctoral students. It has a teaching staff of roughly 4,000 (part-time and full-time) out of a total of 6,200 employees. Twenty-four percent of the 575 professors at the university are women. Of its turnover of 5.5 billion SEK (approx. 850 million USD) in 2012, 29% went to education on basic and advanced level, while 67% went to research and research programs.
Architecturally, Uppsala University has traditionally had a strong presence in the area around the cathedral on the western side of the River Fyris. Despite some more contemporary building developments further away from the centre, Uppsala’s historic centre continues to be dominated by the presence of the university.
Uppsala University research articles from Innovation Toronto
- Anti-ageing treatment for smart windows – October 2, 2015
- New smart robot accelerates cancer research – September 24, 2015
- Smart, ecofriendly new battery to solve problems – September 30, 2014
- Impossible material made by Uppsala University researchers
- Indiana Jones Meets George Jetson
- How the common ‘cat parasite’ gets into the brain
- Fear can be erased from the brain
- Paperweight: A battery made from cellulose
- Wave Power Facility Successful in Sweden
A recent study from Uppsala University shows how smartphones can be used to make movies of living cells, without the need for expensive equipment. The study is published in the open access journal PLOS ONE, making it possible for laboratories around the world to do the same thing.
Live imaging of cells is a very powerful tool for the study of cells, to learn about how cells respond to different treatments such as drugs or toxins. However, microscopes and equipment for live imaging are often very expensive.
In the present study, old standard inverted microscopes that are very abundant at Universities and hospitals were upgraded to high quality live imaging stations using a few 3D-printed parts, off-the-shelf electronics, and a smartphone. It was shown that the resultant upgraded systems provided excellent cell culture conditions and enabled high-resolution imaging of living cells.
“What we have done in this project isn’t rocket science, but it shows you how 3D-printing will transform the way scientists work around the world. 3D-printing has the potential to give researchers with limited funding access to research methods that were previously too expensive,” says Johan Kreuger, senior lecturer at the Department of Medical Cell Biology at Uppsala University.
“The technology presented here can readily be adapted and modified according to the specific need of researchers, at a low cost. Indeed, in the future, it will be much more common that scientists create and modify their own research equipment, and this should greatly propel technology development,” says Johan Kreuger.
Learn more: Live cell imaging using a smartphone
An environmentally friendly, efficient and low-cost method for hydrogenation of graphene with visible light has been developed by researchers at Uppsala University and AstraZeneca Gothenburg, Sweden. The research study is presented in an article in Nature Communications.
The study shows that the two-dimensional and atom-thin carbon material graphene reacts with formic acid in a water solution upon irradiation with visible light. In the reaction, formic acid acts as masked hydrogen and a material is produced where hydrogen extensively has been added to graphene. One says that graphene has been hydrogenated. The study was performed by Assoc. Prof. Henrik Ottosson’s research group at the Department of Chemistry – Ångström Laboratory, together with colleagues in Chemistry, Physics and Engineering at Uppsala University and at AstraZeneca Gothenburg.
“The reaction is convenient and cheap, and hydrogenated graphene may be applied within areas such as hydrogen storage. Additionally, upon functionalization of graphene one can open a band gap and this fact is of high relevance for electronics applications”, says Henrik Ottosson.
Yet, graphene research is a side-project in Henrik Ottosson’s group. The group normally studies the behaviours of various aromatic hydrocarbons upon irradiation, and they apply a rule, the so-called Baird’s rule, which can be derived through chemically applied quantum mechanics.
Chemical compounds that are aromatic have an inherently high stability and often they are not easy to degrade. Benzene is the most well known aromatic compound and more than half of all known chemical compounds contain aromatic groups.
The high stability of aromatic compounds is explained by Hückel’s ‘4n+2’ rule, but this rule is only valid for compounds in their electronic ground states. Upon exposure to light of a certain wavelength, the aromatic compounds reach electronically excited states. According to Baird, compounds that are aromatic in the ground state become antiaromatic and reactive in the excited state. The rule, neglected for decades, can now be used to describe various behaviours of aromatic compounds when irradiated.
Using Baird’s rule, Henrik Ottosson’s group develops new light-initiated reactions. First, they studied addition of hydrosilanes to benzenes, naphthalene and gradually larger polycyclic aromatic hydrocarbons (hydrosilanes are compounds that can be regarded as heavy analogues of hydrogen). Despite the fact that it is not possible to explain if, and how, Baird’s rule can be applied to graphene (an essentially infinitely large polycyclic aromatic hydrocarbon), the group explored graphene chemistry and found a very efficient addition reaction when using formic acid.
At AstraZeneca one sees interesting possibilities for the future:
“It has become more common to apply light-initiated reactions during the development of new molecules in our drug research programs. We challenge ourselves to continuously develop more efficient and environmentally friendly chemical methods. The recent progress we have seen in photochemistry, highlighted by the results herein, will increase our opportunities to access chemistry that no one thought possible a few years ago. In addition, graphene based materials have exceptional inherent properties. There is a wealth of possible applications that could result in the next biomedical revolution”, says Joakim Bergman, Innovative Medicines and Early Development Biotech Unit AstraZeneca Gothenburg.
Being able to determine magnetic properties of materials with sub-nanometer precision would greatly simplify development of magnetic nano-structures for future spintronic devices. In an article published in Nature Communications Uppsala physicists make a big step towards this goal – they propose and demonstrate a new measurement method capable to detect magnetism from areas as small as 0.5 nm2.
Due to the ever-growing demand for more powerful electronic devices the next generation spintronic components must have functional units that are only a few nanometers large. It is easier to build a new spintronic device, if we can see it in a sufficient detail. This becomes more and more tricky with the rapid advance of nano-technologies, especially when we need not only an overall picture “how the thing looks”, but also know its physical properties at nano-scale. One of instruments capable of such detailed look is a transmission electron microscope.
Electron microscope is a unique experimental tool offering to scientists and engineers a wealth of information about all kinds of materials. Differently from optical microscopes, it uses electrons to study the materials, and thanks to that it achieves an enormous magnification. For example, in crystals one can even observe individual columns of atoms. Electron microscopes routinely provide information about structure, composition and chemistry of materials. Recently researchers found ways to use electron microscopes also for measuring magnetic properties. There, however, atomic resolution has not been reached so far.
A team of three physicists from Uppsala University – Ján Rusz, Jakob Spiegelberg and Peter Oppeneer, together with colleagues from Nagoya University (Japan) and Forschungszentrum Jülich (Germany) have developed and experimentally proven a new method, which allows to detect magnetism from individual atomic planes. The area of the sample, from which a magnetic signal was detected, is about a trillion (1012) times smaller than that of an average grain of sand.
‘The discovery of this method came from an unexpected result obtained from computer simulations. It was a surprise, which made us dig deeper into it. Thanks to the international collaboration our curious theoretical observation was soon after followed by an experimental confirmation’, says Ján Rusz.
A significant advantage of this new method is its ease of application. Modern transmission electron microscopes can apply the method right away, without any need of modifications or special equipment.