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Crossing the blood-brain barrier is a vital prerequisite to solving some of the world’s most devastating and difficult to treat diseases. ALS, Parkinson’s, and Alzheimer’s are examples of neurodegenerative and central nervous system (CNS) diseases 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 barriera cellular lining that creates a divide between the brain and 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 challengethe hematopoietic stem cell (HSC). HSCs have the ability to differentiate into multiple cell types; importantly, some become so-called 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 returned 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 the missing or faulty gene by secreting the gene product — which is a protein or enzyme — into the brain where it can be taken up by defective neurons, thus correcting the underlying deficiency causing the disease. 

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

Foundational research in a rare disease called metachromatic leukodystrophy and other neurometabolic and neurodegenerative conditions has led to an understanding of how HSC gene therapy can make a difference in the CNS and potentially prevent deterioration in the brain. And there is reason to believe the HSC gene therapy approach could be used to deliver therapeutic genes or proteins for other less-rare neurodegenerative conditions — like ALS and certain genetic subsets of dementia — that have high unmet need. 

To learn more about HSC gene therapy, visit