New thesis paving the way for effective drug delivery to the brain

Our brain is a complex organ whose many vital functions are protected by the blood-brain barrier: A filter that restricts which substances are allowed to enter the brain. While the barrier stops toxic substances, it also poses a challenge to deliver drugs to the brain. One strategy to cross this layer is to load the drug onto transport proteins, and in a new thesis, Frida Bällgren, PhD student at the Department of Pharmacy, presents new findings about the proton-coupled organic cation antiporter.

“This transporter is already used for several existing drugs and shows great potential to utilize for future drug candidates. Nevertheless, further knowledge is needed about its properties to make full use of it, and in my work, we have studied it from a number of relevant aspects. These include whether the uptake of drugs observed in the brains of rats is also existent in the – in terms of species – more human-like pigs. If the state of disease affects the need for dose adjustments and which methods enables predictions of brain drug levels during early development and in clinic,” says Frida Bällgren.

In her thesis, Frida Bällgren states that only minor differences prevail in the uptake of the drug oxycodone in comparative studies in rats and pigs. Her results also show that the transporter remains active in states of inflammation albeit with lower drug concentration in the brain as a consequence. Additionally, no differences in brain drug delivery between male and female animals were identified.

“Among the thesis clinically interesting results is that our study indicates a somewhat higher drug concentration in the brain compared to that in the cerebrospinal fluid of the spinal cord, which differs from what is often assumed. This gives us reason to assume that our work can reduce the risk of overdose based on cerebrospinal fluid samples during ongoing treatment. Another scientifically relevant observation is that cell models offer promising tools for early analysis of drug potential in terms of uptake in the brain, which might both reduce the need for animal studies and speed up the process to develop new drugs.”

In conclusion, Bällgren notes that the antiporter system offers a promising strategy to improve specific drug deliveries to the brain and treatment of its diseases. Still, she accentuates, there is a need for additional knowledge about which proteins that control the transporter’s functions and – in the next step – its occurrence and activity in a human brain.

“These are questions that have been in focus for the past decades without science being able to answer them. At the same time, this knowledge is necessary if the research in our field is to take to the next important leap. On the other hand: once there, I am convinced that the road forward is open.”

text: Magnus Alsne, photo: Mikael Wallerstedt, private