There is no known<unk> ure for Niemann–Pick type<unk> , nor is there any FDA-standard approved disease modifying treatment. Supportive<unk> are is essential and substantially improves the quality of life of people affected by NPC. The therapeutic team may include specialists in neurology, pulmonology, gastroenterology, psychiatrist, orthopedics, nutrition, physical therapy and occupational therapy. Standard medications used to treat symptoms<unk> an be used in NPC patients. As patients develop difficulty with swallowing, food may need to be softened or thickened, and eventually, parents will need to<unk> onsider placement of a gastrostomy tube (g-tube, feeding tube). Arimoclomol In 2014, the European Medicines Agency (EMA) granted orphan drug designation to arimoclomol for the treatment of Niemann–Pick type<unk> . This was followed in 2015 by the U.S. Food and Drug Administration (FDA). Dosing in a placebo-controlled phase II/III<unk> linical trial to investigate treatment for Niemann–Pick type<unk>  (for patients with both type<unk> 1 and<unk> 2) using arimoclomol began in 2016. Arimoclomol, which is orally administered, induces the heat shock response in<unk> ells and is well tolerated in humans. In 2018, the Sponsor announced the trial did not meet either its primary or secondary endpoints. On July 17, 2021, the US Food and Drug Administration rejected the New Drug Application for Arimoclomol, and issued a<unk> omplete response letter to the<unk> ompany Sponsor. Hydroxypropyl-beta-cyclodextrin (HPbCD) In April 2009, hydroxypropyl-beta-cyclodextrin (HPbCD) was approved under<unk> ompassionate use by the U.S. Food and Drug Administration (FDA) to treat Addison and<unk> assidy Hempel, identical twin girls suffering from Niemann–Pick type<unk>  disease. Medi-ports, similar to ports used to administer<unk> hemotherapy drugs, were surgically placed into the twins'<unk> hest walls and allow doctors to directly infuse HPbCD into their bloodstreams. Treatment with<unk> yclodextrin has been shown to delay<unk> linical disease onset, reduced intraneuronal storage and secondary markers of neurodegeneration, and significantly increased lifespan in both the Niemann–Pick type<unk>  mice and feline models. This is the second time in the United States that<unk> yclodextrin alone has been administered in an attempt treat a fatal pediatric disease. In 1987, HPbCD was used in a medical<unk> ase involving a boy suffering from severe hypervitaminosis A. On May 17, 2010, the FDA granted Hydroxypropyl-beta-cyclodextrin orphan drug status and designated HPbCD<unk> yclodextrin as a potential treatment for Niemann–Pick type<unk>  disease. On July 14, 2010, Dr.<unk> aroline Hastings of UCSF Benioff<unk> hildren's Hospital Oakland filed additional applications with the FDA requesting approval to deliver HPbCD directly into the<unk> entral nervous systems of the twins in an attempt to help HPbCD<unk> ross the blood–brain barrier. The request was approved by the FDA on September 23, 2010, and bi-monthly intrathecal injections of HPbCD into the spine were administered starting in October 2010. On December 25, 2010, the FDA granted approval for HPbCD to be delivered via IV to an additional patient, Peyton Hadley, aged 13, under an IND through Rogue Regional Medical<unk> enter in Medford, Oregon. Soon after in March 2011, approval was sought for similar treatment of his sibling, Kayla, age 11, and infusions of HPbCD began shortly after. Both have since begun intrathecal treatments beginning in January 2012. In April 2011, the National Institutes of Health (NIH), in<unk> ollaboration with the Therapeutics for Rare and Neglected Diseases Program (TRND), announced they were developing a<unk> linical trial utilizing<unk> yclodextrin for Niemann–Pick type<unk>  patients. On September 20, 2011, the European Medicines Agency (EMA) granted HPbCD orphan drug status and designated the<unk> ompound as a potential treatment for Niemann–Pick type<unk>  disease. On December 31, 2011, the FDA granted approval for IV HPbCD infusions for a fifth<unk> hild in the United States,<unk> hase DiGiovanni, under a<unk> ompassionate use protocol. The<unk> hild was 29 months old at the time of his first intravenous infusion, which was started in January 2012. Due to unprecedented<unk> ollaboration between individual physicians and parents of<unk> hildren afflicted with NPC, approximately 15 patients worldwide have received HPbCD<unk> yclodextrin therapy under<unk> ompassionate use treatment protocols. Treatment involves a<unk> ombination of intravenous therapy (IV), intrathecal therapy (IT) and intracerebroventricular (ICV)<unk> yclodextrin therapy. On January 23, 2013, a formal<unk> linical trial to evaluate HPβCD<unk> yclodextrin therapy as a treatment for<unk>  was announced by scientists from the NIH's National<unk> enter for Advancing Translational Sciences (NCATS) and the Eunice Kennedy Shriver National Institute of<unk> hild Health and Human Development (NICHD). In January 2021, the Sponsor (Mallinckrodt Pharmaceuticals)<unk> oncluded that the benefit / risk balance for HPβCD<unk> yclodextrin (adrabetadex) for the treatment of neurologic symptoms of NPC was negative, and that the risks associated with the treatment outweigh the potential benefit. Effective immediately, Mallinckrodt recommended that treatment with adrabetadex be discontinued as soon as possible, with the appropriate physician oversight. N-Acetyl-Leucine N-Acetyl-Leucine is an orally administered, modified amino acid that is being developed as a novel treatment for multiple rare and<unk> ommon neurological disorders by IntraBio Inc (Oxford, United Kingdom). N-Acetyl-Leucine has been granted multiple orphan drug designations from the U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of various genetic diseases, including Niemann-Pick Disease Type<unk> . The US FDA has granted IntraBio a Rare Pediatric Disease Designation for N-Acetyl-Leucine for the treatment of NPC. Observational studies in NPC patients have demonstrated the symptomatic, as well as disease-modifying, neuroprotective effect of treatment. These studies further demonstrated that the treatment is well tolerated, with a good safety profile. In September 2020, IntraBio announced the successful results of a multinational<unk> linical trial with N-acetyl-L-leucine (IB1001) for NPC, which demonstrated IB1001 demonstrated a statistically significant<unk> hange in both primary and secondary endpoints, and<unk> linically meaningful improvement in symptoms, functioning, and quality of life. IntraBio is also<unk> onducting parallel<unk> linical trials with N-Acetyl-L-Leucine for the treatment of GM2 Gangliosidosis (Tay-Sachs and Sandhoff) and Ataxia-Telangiectasia. 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<unk> ells. It has been shown to delay the onset of disease in the NPC mouse, and published data from a multi-center<unk> linical trial of Miglustat in the United States and England and from<unk> ase reports suggests that it may ameliorate the<unk> ourse of human NPC. Several other treatment strategies are under investigation in<unk> ell<unk> ulture and animal models of NPC. These include,<unk> holesterol mobilization, neurosteroid (a special type of hormone that affects brain and other nerve<unk> ells) replacement using allopregnanolone, rab overexpression to bypass the trafficking block (Pagano lab) and<unk> urcumin as an anti-inflammatory and<unk> alcium modulatory agent. The pregnane X receptor has been identified as a potential target. Neural stem<unk> ells have also been investigated in an animal model, and<unk> lear evidence of life extension in the mouse model has been shown. Low<unk> holesterol diets are often used, but there is no evidence of efficacy. Gene therapy is being used<unk> linically to treat genetic diseases including haemophilia and spinal muscular atrophy. It has been used preclinically, in a mouse model of Niemann-Pick type<unk> , 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<unk> apsid<unk> apable of delivering genes to the<unk> entral nervous system following intravenous injection, was given to Niemann-Pick type<unk>  mice at around four weeks of age; this resulted in extended lifespan and improved weight gain.
Niemann–Pick disease, type C
Niemann–Pick disease, SMPD1-associated
Wilson–Mikity syndrome
Haemochromatosis type 3
Hemochromatosis type 4
Wilson's disease
Mowat–Wilson syndrome
Bannayan–Riley–Ruvalcaba syndrome