2022: Advancing across the blood-brain barrier

The brain is protected by the blood-brain barrier, a multi-layered structure which helps to protect it from the invasion of pathogens or unwanted substances and limits drug transport into the brain via the bloodstream. Here, Dr Oliver Ernst and Dr Heiko Manninga from German biotech company NEUWAY Pharma share details of their targeted drug delivery technology, EnPC, which potentiates multi‑cargo BBB delivery including nucleic acids, small molecules and antibodies.

The blood-brain barrier (BBB) is a highly regulated and efficient barrier that provides a sanctuary for the brain. It protects and regulates a fine-tuned equilibrium, only allowing selective transport of molecules that are essential for the brain’s function. Despite the rapid development in our understanding of the molecular structure of the BBB and advances in medical technology, it remains a challenge to treat brain- or central nervous system (CNS)‑associated diseases. This is not due to a lack of suitable or effective drugs, but instead relates to the inability of many therapeutic molecules to cross the BBB to reach the specific areas of need.

Current treatment landscape

The protective function of the BBB arises from the tight connections of the brain’s capillary cells preventing the non-selective crossing of unwanted substances or pathogens into the brain and CNS. This system, however, does allow the passage of certain small molecules via free diffusion, providing they have a molecular weight <400 Dalton and form less than eight hydrogen bonds.1 Given that most potential therapeutics lack these properties and such adaptation would require additional research, time and money, there is little choice aside from applying the drug directly into the brain or CNS.

In 2016, the drug nusinersen, marketed as Spinraza, was the first to be approved for the treatment of spinal muscular atrophy, a severe CNS disease where a specific genetic mutation leads to the reduced expression of a protein necessary for neuron survival. To increase its expression levels, the drug is administered directly to the CNS using intrathecal injection. Besides the complex and painful administration, this drug is listed among the most expensive therapeutics worldwide,2 with costs in the region of $125,000 per injection.

As such, alternative therapies with more convenient application technologies become tremendously valuable.