01 MARCH 2019 P.M.Fornasari

On average, people are living longer than ever before, and that’s good news. However, ageing populations mean higher rates of certain illnesses, such as neurodegenerative disorders. A prominent example of is Parkinson’s disease, a medical condition that already affects 6.5 million people worldwide. This number is expected to more than double by 2030.

Cell replacement therapy is considered the most promising treatment for Parkinson’s disease currently being developed. It consists of transplanting fresh cells into the brain to replace the degenerating neurons. But a major challenge for researchers is working out how to control the behaviour of these newly implanted neurons, which need to rewire themselves into the brain in a specific manner, as the degenerative neurons they replace have their bodies in a particular region of the brain and extend their “arms” (long protrusions called axons) in another region, several centimetres away. The aim of the Magneuron project is to work out how to control the new neurons, so that they implant themselves and function correctly.

http://magneuron.eu/images/video/spacemode.mp4

Magnetogenetics, a novel way of controlling cells

So, how can we control cells in a human body? We need a form of remote control to tell them what to do and where to go. Some years ago, we had the idea of using magnetic nanoparticles and magnets, rather like how children use magnets below a sheet of paper to move magnetic objects as if by magic. We thought: why not do the same but within cells? That’s how it started, as a crazy idea that turned into an international scientific project.

There were several challenges on the way. First we needed to know whether or not we could move magnetic nanoparticles inside cells. In 2013, we did a proof of concept and showed that indeed we were able to do so. Second, the magnetic nanoparticles had to provide instructions for the cells, telling them to move or grow in a specific direction. To do this, we thought of hijacking the signalling machinery of cells. Cells coordinate their activities thanks to an incredibly complicated molecular circuitry: more than thousands of biochemical reactions, highly regulated in space and time, are taking place at any one time. We decided to cover the surface of our magnetic nanoparticles with specific proteins that can act as triggers for intracellular signalling. We demonstrated this idea by forcing a cell to extend its body along an imposed direction. The signalling protein that we attached to the magnetic nanoparticles was produced by the cell (“genetically encoded”), thus we coined the term “magnetogenetics” for this novel technology.

The Magneuron project

In 2016, we decided to go one step further and try to apply our methodology as an innovative treatment for Parkinson’s disease. We applied for and received FET Open funding, which enabled us to gather a consortium of 6 research teams from France, the UK, and Germany.

The general idea of the Magneuron project is to use magnetic nanoparticles to direct the growth of neurons’ arms in the right direction once the engineered cells are implanted in the patient’s brain. Like moving a piece of iron across a sheet of paper with a magnet hidden below, the magnetic nanoparticles are accumulated on one side of the cell. Thanks to specific proteins attached to their surface, the magnetic nanoparticles induce a signalling cue that orients the growth of cells.

EU funding has had a profound impact on the project, acting as a formidable accelerator of scientific progress. Instead of doing our own work and waiting for the rest of the scientific community to react to our findings, now we work in close collaboration with chemists, biophysicists, neurobiologists, Parkinson’s specialists, and experts in cell therapy. Our European consortium gathers people with very different research questions, which we can address as a collective. It pushes us to move beyond fundamental science and get our hands on applied problems. Now that the technique we have devised is mature enough, we are moving on to real neurons and we are applying our method to living cells. Ultimately we would like to perform a proof of concept using brain slices from rats: a challenging task, but very close to the situation we would find in a human patient’s brain. There are still hard obstacles on the way, but for we have a very innovative tool with great potential. We expect that magnetogenetics could be effective in treating Parkinson’s disease in less than 10 years.