1. BioNPC


Clinical trial started on March 01, 2011


Niemann-Pick disease type C (NPC) is a lipid storage disease that can present in infants, children, or adults. Neonate respiratory failure from infiltration of the lungs. Other infants, without liver or pulmonary disease, have hypotonia and developmental delay. The classic presentation occurs in mid-to-late childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy (VSGP), and dementia. Dystonia and seizures are common. Dysarthria and dysphagia eventually become disabling, making oral feeding impossible; death usually occurs in the late second or third decade from aspiration pneumonia. Adults are more likely to present with dementia or psychiatric symptoms.

New methods, such as mass-spectrometry, provide a good chance of characterizing the blood (plasma) of affected patents for specific metabolic alterations that in the future will allow us to diagnose the disease earlier, with higher sensitivity and specificity. In a pilot study Lyso-SM509 was identified as a sensitive and specific biomarker. The structure and pathophysiological role will have to be elucidated further; however preliminary data suggests that Lyso-SM509 is a feasible biomarker for NPC. After the verification of Lyso-SM509 as a biomarker for NPC, validation of Lyso-SM509 in saliva will allow for an easier detection method in the future.

Although NPC is a pan-ethnic disorder, the prevalence of this autosomal-recessive disorder is elevated in countries with a higher frequency of consanguinity.

Therefore, we estimate that every 300th newborn in some countries may be eligible for inclusion due to high-grade suspicion of NPC. The validation of this new biochemical marker from the plasma and saliva of the affected patients is the goal of this study.

Background information

What is NPC?

The diagnosis of NPC is confirmed by biochemical testing that demonstrates impaired cholesterol esterification and positive filipin staining in cultured fibroblasts. Biochemical testing for carrier status is unreliable. Most individuals with NPC have NPC1, caused by mutations in the NPC1 gene; fewer than 20 individuals have been diagnosed with NPC2, caused by mutations in the NPC2 gene. Molecular genetic testing of the NPC1 genes detects disease-causing mutations in approximately 94% of individuals with NPC. Such testing is available clinically.

NPC is inherited in an autosomal recessive manner. Each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. The phenotype (i.e., age of onset and severity of symptoms) usually runs true in families. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible when the two disease-causing mutations have been identified in the family.

The actually used test, Fillipin staining of skin fibroblasts, is invasive and has low sensitivity and specificity. There is an urgent need for the improvement of diagnostic biomarkers.