and C was introduced, and also contained a type D, called the "Nova Scotian type". Genetic studies showed that type D is caused by the same gene as type C1, and the type D designation is no longer used. Research Research has been ongoing to better understand the disease and treatments for it. Pathology The 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 as seen in 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. Curiously, in 2011 fibroblast cells derived from patients with Niemann–Pick type C1 disease were shown to be resistant to Ebola virus because of mutations in the NPC1 protein, which is needed for viral escape from the vesicular compartment. Other studies have uncovered small molecules which inhibit the receptor and may be a potential therapeutic strategy. Treatments under investigation Experimental use of arimoclomol In 2014 the European Medicines Agency (EMA) granted orphan drug designation to arimoclomol for the treatment of Niemann–Pick type C. This was followed in 2015 by the U.S. Food & Drug Administration (FDA). Dosing in a placebo-controlled phase II/III clinical trial to investigate treatment for Niemann–Pick type C (for patients with both type C1 and C2) using arimoclomol began in 2016. Experimental use of 2-hydroxypropyl-β-cyclodextrin Researchers at the University of Arizona first proposed the use of 2-hydroxypropyl-β-cyclodextrins for the treatment of Niemann–Pick Type C1 in 2001. Researchers noted that HPBCDs, with varying levels of 2-hydroxypropyl substitution, had effects in delaying neurological symptoms and in decreasing liver cholesterol storage in a Niemann–Pick mouse model. Later, researchers at the University of Texas Southwestern Medical Center found that when Niemann–Pick type C mice were injected with 2-hydroxypropyl-β-cyclodextrin (HPbCD) when they were seven days old, they showed marked improvement in liver function, much less neurodegeneration and ultimately, they lived longer lives than the mice who did not receive this treatment. These results suggest HPbCD acutely reverses the storage defect seen in NPC. In April 2011, the U.S. National Institutes of Health (NIH), in