Md. Suhail Alam et al. publish in PLoS One on NPC Biomarkers- 10/19/12

(Left, Dr. Suhail Alam. Photo, Rizk, 2012)

Dr. Md. Suhail Alam, together with researchers from the Center for Rare and Neglected Diseases/ Haldar Lab and the Indiana University School of Medicine South Bend, has published the first study to identify 12 genes in the brains of NPC mice, whose protein expressions have the potential to function as plasma markers for lysosomal storage disorders, including Neimann Pick Type C. The identification of these potential markers promises to assist in the development of diagnostics for early blood-based detection of lysosomal storage diseases. The study also shows that a type of immune cell, called a neutrophil, builds up abnormally in the liver and spleen of NPC mice. This occurrence was not previously suspected as a factor in NPC (or related disorders), but may worsen disease progression, especially in the liver.

Niemann-Pick type C disease (NPC) is a rare genetic disorder, which results from the inheritance of defective copies of either of the Npc1 or the Npc2 gene. NPC is a lysosomal storage disorder characterized by the accumulation of cholesterol and glycolipids in lysosomes of cells in the body. Lysosomes function inside cells to digest materials taken in from the outside and to clear degraded materials following internal processing. In NPC, this process is disrupted as the protein products of the defective NPC genes fail to transport lipids across the lysosmes. The accumulation of these lipids in the lysosomal compartments effects the brain, liver and spleen, resulting in severe neurological dysfunction, morbidity and mortality.

The study by Alam et al., sought to identify factors associated with NPC disease severity stages (asypmptomatic, early-, and late-) using genome-wide gene expression analysis in the sentinel (disease indicating) organs associated with the disease: brain, liver, and spleen. The researchers found a noticeable increase in the gene expressions related to a dozen genes primarily related to innate immunity, with the expression steadily increased with age in the brain, liver, and spleen. The elevation of neutrophil in NPC mice was also found to be associated with tissue damage in the liver and spleen.

The diagnosis of NPC, as well as other lysosomal storage disorders, has often been delayed because of the lack of simple blood tests for the diseases. In this study, the identification of genetic biomarkers (proteins produced as a result of genetic encoding) further illuminates the biochemical processes of the disease and its stages. The identification of these biochemical markers may make it possible to determine the presence of the disease through a relatively simple blood test in the future. Early diagnosis of NPC and lysosomal disorders is linked to earlier treatment and better outcomes for patients.

To read the paper in PLoS ONE (open access)...

(Left) The paper's second author, Ms. Michelle Getz, research technician for the Haldar Lab, contributed her expert skills and understanding of the mouse model and labratory methods to achieve critical portions of the experimentation. (Photo, Rizk, 2012)

Genomic Expression Analyses Reveal Lysosomal, Innate Immunity Proteins, as Disease Correlates in Murine Models of a Lysosomal Storage Disorder. Md. Suhail Alam 1,2, Michelle Getz 1,2, Innocent Safeukui 1,2, Sue Yi 1,2, Pamela Tamez 1,2, Jenny Shin 1,2 , Peter Velázquez 1,3 , Kasturi Haldar 1,2* (2012) PLoS ONE 7(10): e48273. doi:10.1371/journal.pone.0048273


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