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The brain is well protected by the blood–brain barrier. This means, however, that drugs have difficulty penetrating the brain. But some of the body's own cells can cross the barrier, and postdoc at DTU Health Technology Raphael Ferreira wants to exploit this for the treatment of brain diseases. 

Cell therapy for the treatment of neurodegenerative brain diseases such as Alzheimer's and Parkinson's is still at the experimental stage, but expectations are high. This includes cell therapy based on the patient's own blood stem cells — immature cells that are able to enter the brain and develop into immune-like cells. They release substances that can dampen inflammation, protect existing nerve cells, and clear away toxic protein deposits typically seen in Alzheimer’s and Parkinson’s disease. The cells do not cure the disease, but can potentially slow progression and alleviate symptoms. 

Until now, however, trials have shown that it is difficult to get enough fully developed cells to reach the diseased brain tissue. 

That is the background for the research project that Raphael Ferreira can now launch with support from the Lundbeck Foundation. 

"Timing in relation to the cells' development is crucial for the effect. If we can get just 10 to 20 per cent more cells there in time, it could mean the difference between life and death," he says. 

The project aims to develop a gene-editing platform using a specialised, advanced tool that Raphael Ferreira has specialised in: multiplexed gene insertion. With it, researchers can edit several genes simultaneously and reinsert them into the cell, rather than editing one gene at a time. 

"You need to equip the cells for a very complex process. You have to remove or add genes and reintroduce the cells into the spinal cord — and from there they must enter the bloodstream and pass through the blood–brain barrier into the brain. They need to reach the right place in the brain and they need to develop. That is why it is important to make several edits at once," explains Raphael Ferreira, who plans to edit around ten genes in the project. 

He has previously developed a platform based on the CRISPR gene-editing tool for editing multiple genes at once. He now plans to use it to optimize and adapt blood stem cells. 

The edits have three goals: to enhance the cells' therapeutic properties, to promote the cells' journey from bone marrow to the brain, and to ensure that the cells arrive in time. The trial is targeted at a rare, hereditary brain disease. 

The first step will be to identify, through mouse experiments, which genes need to be edited and how this can be done safely. Gene editing puts stress on cells and, in the worst-case scenario, can lead to the development of cancer. Finally, the researchers will edit the selected genes all at once and test the effect. 

Although the platform is being developed for blood stem cells and the treatment in the project is targeted at a specific brain disease, the plan is for the platform to be adaptable to other types of cells and other brain diseases. 

Most important in the long run for Raphael Ferreira is the end product: a treatment that doctors can one day offer their patients. 

But here and now, he looks forward to establishing his own research group. 

"I have had a fantastic mentor myself, so I look forward to this new journey, where I will lead a group and help other researchers on their way," he says.