Spatial lipid analysis suggests new paths for Krabbe disease treatment
6 Jul 2026
Discover how Prof. David Muddiman from North Carolina State University is advancing our understanding of globoid cell leukodystrophy (GLD) or Krabbe disease through cutting‑edge mass spectrometry imaging. In this SelectScience video, he shares how using IR‑MALDESI and parallel reaction monitoring to map psychosine accumulation in the brain offered new insight into early neurological changes and the potential for targeted stem‑cell interventions, while also suggesting how more precise psychosine mapping could support an earlier, more confident diagnosis.
This video was filmed at ASMS 2026.
Video transcript
Show transcript
GLD, also known as Krabbe disease, was discovered by a Danish scientist in the early 1900s, and it’s usually diagnosed when fine motor skills are lacking in infants, usually the age of two or three years of age. By the time they’re diagnosed, there’s very little ability to turn the disease around, and so it’s a fatal disease, unfortunately.
But if it can be detected early, and it’s detected in several different ways, you can look at the GAL‑C enzyme activity in red blood cells, or you can look at the psychosine levels that are building up in the bloodstream. And so low GAL‑C enzyme activity or high psychosine levels in the blood can be a signature for the disease. And if it can be detected early, then stem cell treatment might be invoked to try to reverse the disease and give a longer life to that individual.
So we use IR‑MALDESI as one of the key tools in our laboratory that does mass spectrometry imaging for spatial biology, and we do that using high‑resolution accurate mass on an Orbitrap mass spectrometer. That allows us to be very confident that we can locate where the cycosine occurs, and when we know where in the brain it occurs, we know what functions it can change in the body. We found it in the posterior part of the brain, and that is actually where fine motor skills are affected the most. And that’s exactly the hallmark of psychosine buildup in the brain.
The parallel reaction monitoring is a second step in mass spectrometry imaging, which you can do to be very confident, where you take the lipid psychosine and you fragment it and look at the fragments to confer identity of that lipid with high specificity. So it’s a very high‑specificity technology. And by doing that, we were confident that we detected psychosine in the cerebellum, which is right next to the spinal cord. And so the spinal cord is a region where I think things are heading to look to see if it’s actually coming from the spinal cord and bleeding into the brain, or is the psychosine just actually being built up in the cerebellum itself. And that helps us understand where we want to target the treatments to.
So one of the key treatments of it is stem cells. And so you might want to target the stem cells to the cerebellum, where the fine motor skills are affected. And if that could deplete the psychosine buildup, the toxic levels of the lipid, then that might positively impact the patients that have the disease.
What does this video cover?
Topics covered in this video
- How is Prof. David Muddiman using IR‑MALDESI to study Krabbe disease?
- What does psychosine accumulation in the cerebellum reveal about Krabbe disease?
- How can mass spectrometry imaging improve early diagnosis of Krabbe disease in infants?
- Why are GAL‑C enzyme activity and psychosine blood levels key Krabbe disease biomarkers?
- How might targeted stem‑cell therapy address psychosine buildup in the posterior brain?
FAQs
How does Prof. David Muddiman use IR‑MALDESI mass spectrometry imaging to study psychosine in Krabbe disease?
Prof. David Muddiman uses IR‑MALDESI with high‑resolution Orbitrap mass spectrometry to map psychosine accumulation in the brain of patients with globoid cell leukodystrophy (Krabbe disease). This spatial biology approach pinpoints psychosine in regions such as the posterior brain and cerebellum, linking its distribution to impaired fine motor skills and early neurological changes.
What biomarkers and diagnostic strategies for Krabbe disease are highlighted in this SelectScience video?
The video explains that globoid cell leukodystrophy (Krabbe disease) can be detected early by measuring GAL‑C enzyme activity in red blood cells and psychosine levels in the bloodstream. Low GAL‑C activity or elevated psychosine serves as a diagnostic signature. Early detection enables consideration of stem‑cell treatment to potentially reverse disease progression and extend life in affected infants.
How does parallel reaction monitoring enhance psychosine identification for targeted stem‑cell therapy in Krabbe disease?
Parallel reaction monitoring is used as a second mass spectrometry step to fragment the lipid psychosine and analyze its fragments with high specificity. This confirms psychosine in the cerebellum near the spinal cord, clarifying whether it originates from the spinal cord or accumulates locally. These insights guide targeted stem‑cell interventions to the cerebellum to reduce toxic psychosine buildup and improve fine motor function.