future opportunities to develop n-acetyl-leucine include lewy body dementia, amyotrophic lateral sclerosis, restless leg syndrome, multiple sclerosis, and migraine. other treatments under investigation one drug that has been tried is miglustat. miglustat is a glucosylceramide synthase inhibitor, which inhibits the synthesis of glycosphingolipids in cells. it has been shown to delay the onset of disease in the npc mouse, and published data from a multi-center clinical trial of miglustat in the united states and england and from case reports suggests that it may ameliorate the course of human npc. several other treatment strategies are under investigation in cell culture and animal models of npc. these include, cholesterol mobilization, neurosteroid (a special type of hormone that affects brain and other nerve cells) replacement using allopregnanolone, rab overexpression to bypass the trafficking block (pagano lab) and curcumin as an anti-inflammatory and calcium modulatory agent. the pregnane x receptor has been identified as a potential target. neural stem cells have also been investigated in an animal model, and clear evidence of life extension in the mouse model has been shown. low cholesterol diets are often used, but there is no evidence of efficacy. gene therapy is being used clinically to treat genetic diseases including haemophilia and spinal muscular atrophy. it has been used preclinically, in a mouse model of niemann-pick type c, using an adeno-associated virus derived viral vector has been shown to extend lifespan following injection into the lateral ventricles of the neonatal brain. in a separate proof-of-concept study a similar vector, but with a modified capsid capable of delivering genes to the central nervous system following intravenous injection, was given to niemann-pick type c mice at around four weeks of age; this resulted in extended lifespan and improved weight gain. prognosis the lifespan of patients with npc is usually related to the age of onset. children with antenatal or infantile onset usually succumb in the first few months or years of life, whereas adolescent and adult onset forms of niemann–pick type c have a more insidious onset and slower progression, and affected individuals may survive to the seventh decade. adult cases of npc are being recognized with increasing frequency. it is suspected that many patients affected by npc are undiagnosed, owing to lack of awareness of the disease and the absence of readily available screening or diagnostic tests. for the same reasons the diagnosis is often delayed by many years. research directions loss of myelin in the central nervous system is considered to be a main pathogenic factor. research uses animal models carrying the underlying mutation for niemann–pick disease, e.g. a mutation in the npc1 gene niemann–pick type c disease. in this model the expression of myelin gene regulatory factor (mrf) has been shown to be significantly decreased. mrf is a transcription factor of critical importance in the development and maintenance of myelin sheaths. a perturbation of oligodendrocyte maturation and the myelination process might therefore be an underlying mechanism of the neurological deficits. recent neuroimaging studies have shown patients with niemann–pick, type c to have a corpus callosum with microstructural abnormalities. clear reductions in corpus callosum mean thickness and surface area have been shown when compared to age-matched controls. also, studies using diffusion tensor imaging have shown marked reductions in callosal fractional anisotropy, which suggests architectural abnormalities based on the directional flow of water. these conclusions suggest that the corpus callosum plays an important role in the disease and should be explored for use as a biomarker of disease progression. parents of children with npc are being studied in an attempt to gain insight into the ebola virus, which uses the protein encoded by npc1 to enter cells. researchers have found that mice with one normal copy of the npc1 gene are more likely to survive ebola infection than mice with normal two copies of the gene. mice lacking any normal copy of npc1 all survived. studying cells from parents who are npc disease carriers may allow for better understanding of how changes to the npc1 gene affect ebola risk. findings from zhang et al. suggest that npc is a late endocytic trafficking disease resulted, at least in part, from disruption of communication within late endocytic (le) compartments and possibly between le and other subcellular organelles. crosstalk between the late endocytic compartment and other organelles such as mitochondria, endoplasmic reticulum, plasma membrane, as well as early endocytic compartments has become one of the most interesting frontiers in neurondegenerative disease research including alzheimer's disease, parkinson's disease, as well as lysosomal storage disorders.