title: Miglustat treatment may reduce cerebrospinal fluid levels of the axonal degeneration marker tau in niemann-pick type C.
abstract: BACKGROUND
  Niemann-Pick disease type C (NPC) is a lysosomal storage disorder that leads to progressive neurodegeneration. The glucosylceramide synthase blocker miglustat is being used to treat NPC, but monitoring of disease progression and treatment response is difficult. NPC patients have elevated cerebrospinal fluid (CSF) levels of total-tau (T-tau) indicating axonal degeneration, and increased CSF amyloid β (Aβ) indicating abnormal brain amyloid metabolism, but it is unknown if start of miglustat treatment affects these biomarker levels.
  
  
  METHODS
  Biomarkers were measured in serial CSF samples from NPC patients who started miglustat between samplings (N=5), were untreated at both samplings (N=5) or received treatment during the whole study (N=6) (median time between samplings 309 days [range 175-644]). CSF was analyzed for Aβ(38), Aβ(40), Aβ(42), α-cleaved soluble APP, β-cleaved soluble APP, T-tau and phospho-tau.
  
  
  RESULTS
  T-tau levels decreased in patients who started miglustat treatment (median 955 [range 338-1,271]ng/L at baseline vs. 382 [187-736]ng/L at follow-up, p=0.043). Untreated patients and continuously treated patients had stable levels (p>0.05). No changes were seen in the other biomarkers.
  
  
  CONCLUSIONS
  Reduced CSF T-tau suggests that miglustat treatment might affect axonal degeneration in NPC. However, the results must be interpreted with caution and verified in future studies, since this pilot study was small, treatment was not randomized, and patients starting treatment had higher baseline CSF T-tau than untreated patients.
authors: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors: Niklas
authors: N
authors: Mattsson
authors: Henrik
authors: H
authors: Zetterberg
authors: Simona
authors: S
authors: Bianconi
authors: Nicole M
authors: NM
authors: Yanjanin
authors: Rao
authors: R
authors: Fu
authors: Jan-Eric
authors: JE
authors: Månsson
authors: Forbes D
authors: FD
authors: Porter
authors: Kaj
authors: K
authors: Blennow