Mutations in the G Protein Coupled Receptor (GPCR) Gene Family in Melanoma

Using exon capture and next generation sequencing approaches to analyze the entire G protein coupled receptor (GPCR) gene family in melanoma, the researchers at the NIH have identified several novel somatic (e.g., tumor-specific) alterations. GPCRs play an integral part in regulating physiological functions and the importance of these molecules is evident by the fact that approximately half of the current FDA approved therapeutics target GPCRs or their direct downstream signaling components.

 

Treatment of Oculocutaneous/Ocular Albinism and for Increasing Pigmentation

Albinism (also called achromia, achromasia, or achromatosis) is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect in any one of a number of proteins involved in the production of melanin.  Certain forms of albinism are known to be due to mutations in tyrosine metabolism.  In oculocutaneous albinism (OCA), pigment is lacking in the eyes, skin and hair.  In ocular albinism, only the eyes lack pigment.  Patients with albinism experience varying degrees of vision loss associated with foveal hypoplasia, nystagmus

Assay for Predicting the Time of Onset of Niemann-Pick Disease Type C (NPC)

Niemann-Pick Disease, type C (NPC) is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking. Mutation of NPC1 causes intracellular accumulation of unesterified cholesterol in late endosomal/lysosomal structures and marked accumulation of glycosphingolipids, especially in neuronal tissue. Thus, NPC patients generally present with hepatosplenomegaly (enlargement of liver and spleen) and neurological degeneration.

Codon-Optimized Gene Therapy for Niemann-Pick Disease Type C

Niemann Pick Disease Type C (NPC) is a rare and fatal, autosomal recessive, neurodegenerative disease that can present in infants, children, or adults. Most patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking, which results in intracellular accumulation of unesterified cholesterol in late edosomal/lysosomal structures and of glycosphingolipids, especially in neuronal tissue. No curative therapy exists at present.

Non-invasive Pan-Cancer Detection Method

One of four deaths in the United States is due to cancer despite an emphasis on prevention, early detection, and treatment that has lowered cancer death rates by 20% in the past two decades. Further improvements in survival rates are likely to come from improving the limits of detection sensitivity at earlier stages of cancer. New approaches that rely heavily on genomic information, however, may change future testing strategies.

Gene Therapy for Niemann-Pick Disease Type C

Investigators at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) are seeking collaborators to further develop gene therapy to treat Niemann-Pick Disease Type C (NPC). NPC is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking. Mutations of NPC1 cause intracellular accumulation of unesterified cholesterol in late endosomal/lysosomal structures and marked accumulation of glycosphingolipids, especially in neuronal tissue.

Novel Codon-Optimized Gene Therapeutic for Methylmalonic Acidemia

Methylmalonic Acidemia (MMA) is a metabolic disorder characterized by increased acidity in the blood and tissues due to toxic accumulation of protein and fat by-products resulting in seizures, strokes, and chronic kidney failure. A significant portion of MMA cases stem from a deficiency in a key mitochondrial enzyme, methylmalonyl-CoA mutase (MUT), required to break down amino acids and lipids. Currently, there are no treatments for MMA and the disease is managed primarily with dietary restriction of amino acid precursors and liver-kidney transplantation in severe cases.

Mouse Model for Methylmalonic Acidemia, an Inherited Metabolic Disorder

Methylmalonic Acidemia (MMA) is a metabolic disorder affecting 1 in 25,000 to 48,000 individuals globally. MMA is characterized by increased acidity in the blood and tissues due to toxic accumulation of protein and fat by-products resulting in seizures, strokes, and chronic kidney failure. About 60% of MMA cases stem from mutations in the methylmalonyl CoA mutase (MUT) gene encoding a key enzyme required to break down amino acids and lipids. Previous efforts to develop mice with null mutations in MUT have been unsuccessful, as such mutations result in neonatal death.

Glucocerebrosidase Non-inhibitory Chaperones for the Treatment of Gaucher Disease, Parkinson's Disease, and Other Proteinopathies

Gaucher disease is a rare lysosomal storage disease that is characterized by a loss of function of the glucocerebrosidase (GCase) enzyme, which results in a decreased ability to degrade its lipid substrate, glucocerebroside. The intracellular build up of this lipid causes a broad range of clinical manifestations, ranging from enlarged spleen/liver and anemia to neurodegeneration. In Gaucher disease, the loss of GCase function has been attributed to low levels of the protein in the lysosomal compartment, resulting from improper GCase folding and transport.