• Date: January 20, 2021

In the late 19th century, the bacteriologist Paul Ehrlich (Nobel Prize in Medicine 1908) made a revolutionary discovery while conducting one of his famous staining experiments. He injected a dye into the bloodstream of mice that surprisingly stained all organs except the brain and spinal cord. What prevented the dye from entering the brain was a structure now known as the blood-brain barrier. Formed by a layer of capillaries, this barrier allows only select molecules in our blood to enter the brain. 

While keeping out harmful pathogens and toxins, it also blocks the entry of drugs that can potentially cure brain diseases. In fact, more than 98% of drug candidates fail to cross it. To overcome this, a team of researchers at the Institute for Research in Biomedicine (IRB Barcelona) has developed tiny “keys” that can unlock entry points on the blood-brain barrier to let in therapeutic cargoes. With the support of a CaixaImpulse, they recently created a spinoff called Gate2Brain. They are currently testing the ability of their technology to treat diffuse intrinsic pontine glioma (DIPG)—a devastating and incurable childhood cancer. If successful, it could soon be used to treat and even cure numerous other brain diseases. We recently interviewed Gate2Brain CEO Meritxell Teixidó to learn more about this innovative technology.

 


Why is the brain so highly protected compared to other organs?

The brain is probably our most complex and essential organ, but it is also the most vulnerable to damage. That’s why our bodies have evolved the blood-brain barrier to protect it. But this protective barrier also makes it very difficult to treat brain diseases.


How will Gate2Brain help drugs to cross the blood-brain barrier?

The blood-brain barrier is like a brick wall that stops toxins in the blood from entering the brain. This wall has certain gates through which nutrients pass and waste is removed. 

Gate2Brain technology is based on small molecules known as peptides, which are capable of crossing this barrier through various mechanisms. Our objective is to bind therapeutic agents to the peptides so that they act as a 'key', open these gates and transport drugs to parts of the brain that they cannot reach by themselves. 


Why did you choose peptides as the key to crossing the blood-brain barrier?

We were inspired by nature, or more specifically, by venomous animals. Peptides are found in many venoms that have the ability to reach the brain. By studying them, we worked out which part was responsible for that ability and thus developed our 'keys'.


Who will benefit from Gate2Brain technology?

Shockingly, one in four of us will need to be treated for a brain disease in our lifetime. This includes conditions such as Alzheimer's, Parkinson's, schizophrenia, as well as numerous rare diseases and brain tumors. So in reality, all the people for whom there is a drug candidate that cannot reach the brain are the ones who will benefit from our technology.

We are currently testing this technology on a specific illness called diffuse intrinsic pontine glioma (DIPG)—a rare and incurable brain cancer that affects children. In this case, the chemotherapeutic agent really needs a push to reach the brain. 


How has CaixaImpulse helped your project?

CaixaImpulse has helped us to take that leap from the laboratory to the creation of the company, not only in financing, but also in training and mentoring. As a result, we have now launched as a spinoff. From here we hope to further develop our technology in order to cure children and adults alike who suffer from a variety of brain diseases.

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