Crossing the blood-brain barrier is a vital prerequisite to solving some of the world’s most devastating and difficult to treat diseases. Frontotemporal dementia and Alzheimer’s are examples of neurodegenerative diseases of the central nervous system (CNS) that require a therapy that can effectively cross the blood-brain barrier.

The brain is the most important organ in the body and humans have evolved to develop mechanisms to protect it. A key component of that protection is the blood-brain barrier—a cellular lining of the blood vessels that creates a divide between the brain and the general blood circulation.

The blood-brain barrier is responsible for determining which proteins, molecules and cells can cross into the brain to maintain normal brain function. While this difficult-to-cross barrier protects the brain from dangerous toxins and other threats, it also presents a unique set of challenges for treating conditions of the CNS. It means that, for example, certain therapies can have difficulty penetrating the brain.

There is, however, an exceptional cell type that can overcome this challenge—the hematopoietic stem cell, or HSC.

HSCs have the ability to differentiate into multiple cell types; importantly, some are “specialist” cells that can cross the blood-brain barrier and enter the brain.

Scientists are working to harness the power of HSCs for new medicines.

When gene-corrected HSCs are delivered to the blood stream, a subset of these HSCs can develop into cells that have a natural ability to cross the blood-brain barrier and distribute throughout the brain. Once in the brain, these cells further differentiate into specialist cells called microglial-like cells. Because these cells have been genetically modified, they can express a correct version of the missing or faulty gene by secreting the therapeutic protein into the brain where it can be taken up by defective neurons.

These characteristics suggest that HSC gene therapy may offer hope for patients with certain kinds of genetic CNS-related conditions.

Foundational research in rare diseases such as metachromatic leukodystrophy (MLD) and Hurler’s syndrome has led to an understanding of how HSC gene therapy can make a difference in the CNS and prevent deterioration of brain functions. These studies are opening the way to the use of genetically modified HSCs to also treat neurodegenerative diseases, like frontotemporal dementia or Alzheimer’s.

And it is possible that the HSC gene therapy approach could be used to deliver gene-corrected HSCs in other difficult-to-treat tissues and organs. In a form of Crohn’s disease, for instance, specialist cells in the gut wall are defective and cannot detect bacterial invasion which leads to chronic inflammation. The potential of HSC gene therapy to treat this form of Crohn’s disease is now being investigated whereby the ability of gene modified HSCs to migrate into the gut wall and become specialized cells could then detect bacterial invasion and prevent chronic inflammation.

Click here to learn more about the promise of HSC gene therapy.