The Blood-brain barrier (BBB) can block life-saving treatments from entering the brain.
It is a protective barrier that coats the inner surfaces of the blood vessels in your brain. If molecules can’t get through this wall, then drugs can't move from the blood to the brain at all!
If you want to treat a disease like Niemann-Pick type C (NPC), then that barrier can be a problem.
As NPC progresses, the loss of cells in the brain can lead to thinking and memory problems, as well as issues with speech, movement and balance. If medications don’t reach the brain, then we are not effectively treating the major symptoms of this disease.
Reading this, you might now be surprised when I say that the BBB is not bad.
Its role is actually quite important and has likely kept you alive and well even though you may not have realised it.
It’s main job: PROTECT THE BRAIN!
Think of the BBB as a very effective and strict security wall. It blocks 98% of all small molecules in the blood from entering the brain¹.
It’s very selective about what can pass through and rightly so! We don’t want harmful toxins getting into our brains if we can avoid them! Just like a security gate, molecules with the right features get in, while others stay stuck in the blood.
With ageing and some neurodegenerative diseases such as Alzheimer’s disease, the BBB can become leaky or faulty². This means that the security wall has holes in it, and harmful things may be able to get through and hurt the brain, leading to neurological symptoms.
How do we get drugs through the BBB?
Scientists are trying a range of approaches to bypass this screening system.
In some cases, an injection into the spinal fluid via a lumbar puncture (i.e. medication injected via a needle in your back) has been used to bypass the BBB.
As can be seen with the Australian patient being prepped for their infusion from the VTS-270 Clinical Trial in 2019 (see photo).
Spinal fluid flows directly to the brain, so this method can be effective but is invasive. An NP-C treatment (2-Hydroxypropyl-Beta-Cyclodextrin) previously used this method to deliver drugs to patients³ in trials.
Another method was developed by researchers using a virus. As NPC is caused by a lack of NPC protein, scientists decided to modify a virus that can get into specific BBB cells and cause the cell to make more protein⁴. Other research groups are using gene editing technology to genetically change these BBB cells, so they become NPC protein-making factories⁵!
Do we have treatments that cross the BBB in Australia?
Miglustat is an oral therapy that may be used to treat NPC. Miglustat therapy molecules can cross the BBB, which explains why some patients report improvements in neurological symptoms such as ataxia (muscle coordination difficulty), or dysphagia (swallowing difficulty).
It’s exciting to know that the US has approved two treatments, Miplyffa (arimoclomol) and Aqneursa (levacetylleucine) that can cross the BBB, and potentially improve or stabilise neurological symptoms of NPC Disease.
However, these drugs are not yet to be approved for use in Australia, and more work is needed to get them approved and to our shores.
The ANPDF have a webinar coming up which focuses on how the ANPDF, and the Australian community can advocate for treatments to be made available to patients in Australia.
Advocacy is so important in the rare disease space, and we would love for you to come along and learn more about how we can push for access to these new treatments.
Stay supportive and supported,
Ellie
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