We are starting a series of articles designed to support our readers in understand what is going on as new therapies emerge in the research world. We will explore the scientific approaches researchers are investigating for VPS13A and XK diseases.

We will explore three main areas:

• Genetic therapies
• Deep Brain Stimulation (DBS)
• Stem‑Cell approaches. 

Each article breaks down one therapeutic area in clear, accessible language, what it is, how it works, and whether it has any potential applicability for the NA syndromes in the future. At the end of the series, once we’ve explained each of these research areas, we will share a comparison of all three against each other. 

While none of these approaches are ready for clinical use, research is progressing across multiple fronts and we endeavour to share this with you. Understanding the science helps us follow the journey together. 

At the VPS13 Forum on 27 April2026, Dr Chris Stephen from Massachusetts General Hospital in Boston, USA, presented an overview of emerging genetic therapies and how they might one day apply to NA syndromes (see the Forum report). His talk sparked important questions from families about what treatments would be available now, and what may be possible in the future.

Dr Stephen explained that genetic therapies aim to address diseases at their root cause - the gene (encoding for a protein) that isn’t working properly. In both VPS13A and XK diseases (similar to many other genetic disorders), the VPS13A or XK genes contain a change (mutation) that prevents the cell from making a fully functional version of the chorein protein (also known as VPS13A protein) or XK protein. Without these proteins, certain cells (e.g. neurons, red blood cells) become vulnerable over time.

Genetic therapies try to fix this problem in one of three ways:

• Replacing the faulty gene with a healthy one
• Repairing the mutation so the gene works correctly
• Supporting the cell in other ways so it can cope better with the missing protein.

These approaches are not yet applicable for either of the NA syndromes (VPS13A or XK diseases). Before any therapy can be designed, researchers need a detailed understanding of:

• which mutations cause which effects
• how chorein / VPS13A and XK protein works exactly in different cell types
• how to safely deliver a corrected (large) gene into the right brain regions and/or other parts of the body.

And there are many other open questions around this, too, which need to be explored first.

In the wider genetic context, we’ve been asked often about CRISPR (short for “clustered regularly interspaced short palindromic repeats”). We thought it would be helpful to clarify that this is most accurately described as a gene-editing or genome-editing technology. Research scientists use it to selectively modify the DNA of living organisms. In 2023, the UK approved the world’s first CRISPR‑based therapy for sickle cell disease, a major milestone.

However, considering applying CRISPR or other gene therapy methods to NA syndromes is far more complex. At the VPS13 Forum back in November 2023, the conversation on this topic concluded that:

• Everyone with VPS13A disease has 2 copies of the faulty gene, and there are a huge number of different mutations known that cause the disease. At least one of these mutations would need to be corrected to prevent the disease, and to produce normal chorein/VPS13A protein. The brain needs chorein/VPS13A protein, so the faulty gene would need to be repaired or replaced, the protein not removed (as it’s the case for several other genetic disorders).
• Researchers still need to understand exactly how each VPS13A mutation affects the protein and whether it can be corrected.
• For XK the gene is much smaller, and there are fewer mutations, so may be easier to target. People (usually men) with XK disease have one affected XK gene which needs to be corrected.
• The editing of the faulty gene, or the replacement with an unaffected gene needs to be done in the brain, and ideally in all affected regions, some of which are very deep in the brain. Can the gene be delivered by a viral vector such as AAV (short for “adeno-associated virus”, a small, safe virus used in gene therapy to carry healthy genes into human cells)? It’s worth noting that the replacement (not correction of a single mutation) of the complete VPS13A gene is very challenging as it is an extremely large gene.
• Would this only be needed once, or repeated?
• Can we also target other tissues such as heart muscle (in XK), skeletal muscle, and peripheral nerve?
• At present, in most cases people don’t know they have the disease until they develop symptoms. Would the treatment stop the disease progression, or heal affected brain regions? The earlier such a therapy is initiated (ideally during the prodromal (initial, subtle) phase of the disease), the more effective it is likely to be. As the diagnosis of VPS13A/XK disease is often delayed, this represents a particular challenge.
• CRISPR is legal in the UK and USA, but not yet regulated in many other countries.
• Work in related diseases, such as Huntington’s, may offer parallel insights, but NA has its own unique biology. (HD is caused by a completely different type of genetic mutation, a “trinucleotide repeat”, and is autosomal dominant, thus quite different methods are needed to correct the issue)

While CRISPR, as well as other gene therapy methods, is highly specialised and may appear hopeful path for the future, it’s not yet applicable to NA syndromes. More foundational research is needed before gene editing could be considered.

Although these approaches are still at an early stage for NA syndromes, the work being done now is laying the essential groundwork for future progress. Each study, each dataset, and each new insight helps researchers understand the biology more clearly and brings the field one step closer to the point where targeted therapies could be designed and tested. It is careful, methodical science, and, while it takes time, it is moving forward with more momentum and international collaboration than ever before.