Materiały źródłowe

• #1 Niemann-Pick disease – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/niemann-pick/diagnosis-treatment/drc-20355890

  No cure exists for Niemann-Pick disease, but supportive care can help manage symptoms. […] For Niemann-Pick disease type B, olipudase alfa-rpcp (Xenpozyme) is an enzyme replacement for missing or low levels of the sphingomyelinase enzyme. This enzyme replacement may help with lung problems and breathing and lessen the size of the liver and spleen. The medicine also may help height growth in children. It does not help with nerve-related symptoms. […] For people with Niemann-Pick disease type C who have mild to moderate nerve symptoms, a drug called miglustat may be an option. Miglustat is approved for neurological symptoms of Niemann-Pick disease type C in many countries but is not approved by the U.S. Food and Drug Administration for this use in the United States. […] Discuss medicines, including possible side effects, with your doctor or other healthcare professional.

• #2 Niemann Pick Disease

  https://www.brainfacts.org/diseases-and-disorders/neurological-disorders-az/diseases-a-to-z-from-ninds/niemann-pick-disease

  There is currently no cure for Niemann-Pick disease. Treatment is supportive. […] There is currently no effective treatment for persons with type A. Bone marrow transplantation has been attempted in a few individuals with type B. The development of enzyme replacement and gene therapies might also be helpful for those with type B. […] restricting one’s diet does not prevent the buildup of lipids in cells and tissues.

• #3 Sphingomyelinase Deficiency Treatment & Management: Medical Care, Surgical Care, Further Care

  https://emedicine.medscape.com/article/951564-treatment

  The first disease-specific enzyme replacement treatment for non-CNS ASMD, olipudase alfa, was approved by the FDA in August 2022. […] Other medical and surgical care for Niemann-Pick disease (NPD) types A and B are mainly focused on supportive care. […] Adult patients with elevated serum cholesterol due to NPD type B should be treated to bring serum cholesterol concentration into the normal range. […] Transfusion of blood products may be necessary for acute episodes of bleeding secondary to hypersplenism and thrombocytopenia in NPD type B patients. […] Supplemental oxygen may be used for NPD type B patients with symptomatic interstitial lung disease. […] Olipudase alfa is an ASM enzyme that the FDA has approved for the treatment of non-CNS manifestations of ASMD in adult and pediatric patients.

• #4 Niemann-Pick Disease | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25882

  For type A and B Niemann-Pick disease (NPD), there is no cure. Supportive care is the mainstay of treatment. Physicians try to keep low blood lipids levels with statins, and liver functions are monitored. If thrombocytopenia leads to bleeding episodes, transfusion of blood products may be required. For patients with ILD, oxygen is provided. Organ transplant has also been tried but with limited success. Enzyme replacement therapies and gene therapies are undergoing trials and may become the mainstay of treatment in the future.[12] […] For type C disease, supportive care is also the mainstay of treatment. Physical therapy is provided for neurological symptoms. Pain is managed with analgesics. Miglustat is a glucosylceramide synthase inhibitor and helps in Niemann-Pick disease and Gaucher disease by decreasing glucocerebroside production. It is approved in Europe, Canada, and Japan but is not yet approved in the United States.[13]

• #5 First therapy to treat two types of Niemann-Pick disease, a rare genetic metabolic disorder | European Medicines Agency (EMA)

  https://www.ema.europa.eu/en/news/first-therapy-treat-two-types-niemann-pick-disease-rare-genetic-metabolic-disorder

  EMA has recommended granting a marketing authorisation in the European Union (EU) for Xenpozyme (olipudase alfa), a therapy for the treatment of non-central nervous system (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD), a rare and progressive genetic disease. […] Xenpozyme is the first ASMD-specific treatment. This medicine is an enzyme replacement therapy, developed to replace patients deficient or defective enzyme, acid sphingomyelinase (ASM), and thereby reduce fat accumulation within cells and relieve some of the symptoms of the disease. […] The opinion adopted by the CHMP is an intermediary step on Xenpozymes path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation.

• #6 Niemann-Pick disease – Medizinonline

  https://medizinonline.com/en/niemann-pick-disease/

  For pediatric and adult patients with Niemann-Pick disease or ASMD (acid sphingomeyelinase deficiency) type A/B or type B without central nervous involvement, the enzyme replacement therapy olipudase alfa was approved by the EMA in 2022. […] The approval decision is based on data from the ASCEND and ASCEND-Peds clinical trials, which showed clinically relevant improvements in lung function and reductions in spleen and liver volume with olipudase alfa therapy. […] For Niemann-Pick disease types A and B, enzyme replacement therapy with olipudase alfa is available in the EU. […] Type C is treated symptomatically with miglustat.

• #7 Niemann-Pick disease: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001207.htm

  At this time, there is no effective treatment for the neurologic symptoms of type A. Enzyme replacement with olipudase alfa was approved by the FDA in 2022 to treat non-central nervous system symptoms. […] Bone marrow transplants may be tried for type B. Enzyme replacement with olipudase alfa is approved by the FDA to treat non-central nervous system symptoms of type B. Researchers continue to study additional possible treatments, such as gene therapy. […] A medicine called miglustat is available for the nervous system symptoms of type C. […] High cholesterol may be managed with a healthy, low-cholesterol diet or medicines. However, research does not show that these methods stop the disease from getting worse or change how cells break down cholesterol. Medicines are available to regulate or relieve many symptoms, such as sudden loss of muscle tone and seizures.

• #8 Sphingomyelinase Deficiency Treatment & Management: Medical Care, Surgical Care, Further Care

  https://emedicine.medscape.com/article/951564-treatment

  Approval of olipudase alfa arose from the ASCEND and ASCEND-Peds trials. […] Histocompatible hematopoietic stem cell transplantation conducted on a 4-year-old girl with NPD type B was successful in improving sphingomyelinase enzyme levels and improving severe pulmonary disease. […] Lung transplantation has been performed in patients with type B disease, including a successful double-lung transplantation reported by Mora et al, in a male aged 57 years. […] Although patients may have massive splenomegaly, splenectomy should be avoided whenever possible. […] Patients with type A disease may develop respiratory decompensation, requiring inpatient care for stabilization during severe episodes. […] Pediatric patients with NPD type B require frequent meals to promote growth. […] Patients with NPD type B should undergo annual pulmonary function testing and evaluation.

• #9 The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann–Pick Disease: A Comprehensive Review

  https://www.mdpi.com/2218-273X/14/2/211

  Niemann–Pick Disease (NPD) is a rare autosomal recessive disease belonging to lysosomal storage disorders. […] Although several efforts have been made to find an effective therapy for NPD, to date, only limited therapeutic options are available. Enzyme replacement therapy with Olipudase α is the first and only approved disease-modifying therapy for patients with ASMD. A lung transplant and hematopoietic stem cell transplantation are also described for ASMD in the literature. […] Therapeutic strategies in NPD type A and B are still limited and often associated with only mild improvement in the prognosis and quality of life. […] Enzyme replacement therapy (ERT) is the best therapeutic option in NPD and is considered a disease-modifying therapy, able to guarantee the widespread enzyme delivery to the affected organs.

• #10 About NPD – International Niemann-Pick Disease Alliance (INPDA)

  https://www.inpda.org/about-niemann-pick-diseases/

  ASMD Niemann Pick Type A: Unfortunately there is no cure or disease modifying treatment available for this condition. At present, caring for children with Type A involves treating the many symptoms that result from the disease. The main focus of this symptomatic treatment is to ensure that their quality of life is as high as possible. […] ASMD Niemann Pick Type B: There is currently no specific treatment for ASMD NPB, but medications can be taken to treat the symptoms of the illness. […] Genzyme, a Sanofi company, is continuing its clinical development of a potential enzyme replacement therapy, recombinant human acid sphingomyelinase (rhASM), and is actively preparing to initiate two clinical trials. One is a Phase 2/3 adult clinical trial and a second is a Phase 1/2 pediatric trial. For further information you can also visit Genzyme’s clinical trials page.

• #11 Niemann-Pick Disease Type A | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/niemann-pick-disease-type

  There are currently no approved therapies to reverse the effects of Niemann-Pick disease. Current approaches to Niemann-Pick disease type A involve supportive therapies and targeted management for specific symptoms. […] At the Boston Childrens Lysosomal Storage Disorders (BoLD) Program, our team of providers is committed to the care of complex patients.

• #12 Overview of acid sphingomyelinase deficiency and Niemann-Pick disease type C – UpToDate

  https://www.uptodate.com/contents/overview-of-acid-sphingomyelinase-deficiency-and-niemann-pick-disease-type-c

  Disease-modifying therapy for ASMD includes Olipudase alfa. […] Disease-modifying therapies for NPC include approaches such as Levacetylleucine, Arimoclomol, and Miglustat. […] Experimental therapies are also being explored for Niemann-Pick disease.

• #13 FDA Approves First Treatment for Niemann-Pick Disease, Type C

  https://www.prnewswire.com/news-releases/fda-approves-first-treatment-for-niemann-pick-disease-type-c-302254310.html

  Today, the U.S. Food and Drug Administration approved Miplyffa (arimoclomol), an oral medication for the treatment of Niemann-Pick disease, type C (NPC). Miplyffa, in combination with the enzyme inhibitor miglustat, is approved to treat neurological symptoms associated with NPC in adults and children 2 years of age and older. Miplyffa is the first drug approved by the FDA to treat NPC. […] „The first-ever approval of a safe and effective drug option for NPC will undoubtedly support the essential medical needs of those suffering.” […] Miplyffa’s efficacy was demonstrated by the rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS) score in the patients who used miglustat as their background treatment. […] Compared to placebo, Miplyffa resulted in a slower disease progression as measured by the R4DNPCCSS score. […] Miplyffa, along with miglustat, should be taken orally with or without food according to the recommended dose for the patient’s body weight.

• #14 FDA Approves Treatments for Niemann-Pick Disease, Type C

  https://www.pharmtech.com/view/fda-approves-treatments-for-niemann-pick-disease-type-c

  Two drugs, Miplyffa (arimoclomol) and Aqneursa (levacetylleucine), have been approved by FDA to treat neurological symptoms associated with Niemann-Pick disease, type C in adults and children. […] Miplyffa (arimoclomol), approved on September 20, is the first treatment approved by FDA for NPC and is an oral medication used in combination with the enzyme inhibitor miglustat to treat NPC symptoms in adults and children two years of age and older. […] The second drug, Aqneursa (levacetylleucine), was approved on September 24 to treat NPC in adults and children who weight at least 15 kilograms.

• #15 FDA Approves Stand-Alone Therapy Levacetylleucine for Niemann-Pick Disease Type C

  https://www.neurologylive.com/view/fda-approves-stand-alone-thearpy-levacetylleucine-niemann-pick-disease-type-c

  The approval follows phase 3 data that showed significant improvements in neurological symptoms and functional benefit over 12 weeks in patients with Niemann-Pick disease type C. […] According to a new company announcement, the FDA has approved IntraBios levacetylleucine, an agent that ameliorates lysosomal and metabolic dysfunction, as a stand-alone treatment of neurological manifestations in Niemann-Pick disease type C (NPC) among adults and pediatric patients weighing at least 15 kg. […] The approval was based on data from the phase 3 double-blind, placebo-controlled, crossover trial IB1001-301 trial (NCT05163288), which investigated levacetylleucine among 60 patients aged between 5 years and 67 years of age with NPC over 12 weeks. […] „IntraBio has been dedicated to bringing novel treatments to patients with extremely high unmet medical needs like NPC, and today we celebrate a major milestone in this tremendous effort, Mallory Factor, president and chief executive officer at IntraBio, said in a statement.

• #16 FDA Approves Levacetylleucine for Niemann-Pick Disease Type C

  https://www.hcplive.com/view/fda-approves-levacetylleucine-for-niemann-pick-disease-type-c

  FDA Approves Levacetylleucine for Niemann-Pick Disease Type C. The US Food and Drug Administration (FDA) has approved IntraBios levacetylleucine (Aqneursa) for the treatment of neurological symptoms associated with Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing 15 kg. […] In their announcement, IntraBio indicated levacetylleucine is the only FDA-approved stand-alone therapy for the treatment of NPC. […] The FDA approval of levacetylleucine marks a significant breakthrough for those living with NPC, said Laurie Turner, family services manager at the National Niemann-Pick Disease Foundation. […] Treatment approaches have traditionally been unable to address the devastating effects of NPC on a patients daily life. […] Approval of levacetylleucine was awarded based on results from the multinational, randomized, double-blind, placebo-controlled, pivotal IB1001-301 clinical trial.

• #17 Advancements in Niemann-Pick Disease Type C Treatments

  https://www.delveinsight.com/blog/niemann-pick-disease-type-c-treatment

  While the FDA hasn’t granted specific approval for NPC, ZAVESCA/BRAZAVES is approved for managing Gaucher’s disease in the US. Consequently, healthcare practitioners sometimes prescribe this drug off-label to NPC patients. Miglustat operates by impeding the synthesis of glycosphingolipids, a substance that accumulates in the brains of those with NPC. It’s known to decelerate the progression of neurological symptoms associated with the condition. However, it’s important to note that this treatment might not be suitable for every individual affected by NPC. […] Currently, four promising therapies are in the Niemann-Pick Disease Type C pipeline: Arimoclomol by Zevra Therapeutics, AZ-3102 by Azafaros A.G., Trappsol(R) Cyclo or Hydroxypropyl-beta-cyclodextrin by Cyclo Therapeutics, Inc., and IB1001 by IntraBio. These innovative therapies hold the potential to bring much-needed relief to patients and may have a substantial impact on the Niemann-Pick Disease Type C treatment market landscape in the seven major markets over the forecast period from 2023 to 2032, given the absence of approved treatments.

• #18 Consensus clinical management guidelines for Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0785-7

  The following functional assessments should take place at the time of diagnosis or symptom onset and at regular intervals thereafter for optimal symptom control and functional capacity. […] Miglustat, a substrate reduction therapy, is the only licensed disease modifying medicine in the European Union for the treatment of neurological manifestations of patients with NPC disease. […] All patients with a confirmed diagnosis of NPC should be considered for miglustat therapy. […] NPC patients who are pre-symptomatic or have only spleen/liver enlargement should not be offered miglustat. […] Miglustat should not be started in NPC patients with advanced neurological disease/dementia. […] Clinical trials testing the safety and efficacy of intrathecal or intravenous preparations of 2-hydroxypropyl-β-cyclodextrin and oral Arimoclomol are ongoing.

• #19 Niemann-Pick disease – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/niemann-pick/diagnosis-treatment/drc-20355890

  Therapies for all types of Niemann-Pick disease depend on symptoms and may include: […] Physical therapy and occupational therapy can help keep the ability to move as long as possible. Speech therapy may help with talking and swallowing. […] This includes special foods that can be added to the diet when swallowing becomes difficult. […] This can help if the lungs are affected and problems with breathing happen. […] Treatments can help with infections, seizures, muscle movements that can’t be controlled and sleep problems. […] People with Niemann-Pick disease need to see their healthcare professionals regularly, because the disease and its symptoms worsen over time. Research for new treatments is ongoing.

• #20 Advancements in Niemann-Pick Disease Type C Treatments

  https://www.delveinsight.com/blog/niemann-pick-disease-type-c-treatment

  Managing NPC involves a multidisciplinary approach. A team of specialists, including pediatricians, neurologists, ophthalmologists, pulmonologists, gastroenterologists, and other healthcare experts, collaborates to develop a comprehensive treatment plan for affected children. Its also vital to provide psychosocial support to the entire family. Genetic counseling can provide valuable insights for both patients and their families. While there is no cure for NPC, palliative treatments can significantly improve the quality of life. Occupational therapy aids in addressing issues related to posture, speech, and movement, and physical therapy plays a crucial role in maintaining mobility for as long as possible. […] In Europe and Japan, ZAVESCA/BRAZAVES (miglustat) manufactured by Actelion Pharmaceuticals stands as the primary approved therapy for addressing NPC, a rare genetic disorder.

• #21 Niemann-Pick disease | Health Library | Memorial Health System

  https://www.mhsystem.org/health-library/con-20257402/

  Therapies for all types of Niemann-Pick disease depend on symptoms and may include: Speech, physical and occupational therapy. Physical therapy and occupational therapy can help keep the ability to move as long as possible. Speech therapy may help with talking and swallowing. […] Nutrition therapy. This includes special foods that can be added to the diet when swallowing becomes difficult. […] Oxygen therapy. This can help if the lungs are affected and problems with breathing happen. […] Treatment of symptoms. Treatments can help with infections, seizures, muscle movements that cant be controlled and sleep problems. […] People with Niemann-Pick disease need to see their healthcare professionals regularly, because the disease and its symptoms worsen over time. Research for new treatments is ongoing.

• #22 Advancements in Niemann-Pick Disease Type C Treatments

  https://www.delveinsight.com/blog/niemann-pick-disease-type-c-treatment

  Trappsol Cyclo being developed by Cyclo Therapeutics is a proprietary formulation of hydroxypropyl betacyclodextrin and in multiple clinical studies has shown encouraging results to effectively manage the transportation of cholesterol. […] IB1001 (N-acetyl-l-leucine) is being developed for Niemann Pick Disease Type C besides other orphan indications like Tay-Sachs and Sandhoff Disease and inherited Cerebellar Ataxias. […] IntraBio has been granted Orphan Drug Designations, Rare Pediatric Disease Designations by the US FDA and EC for Niemann Pick Disease Type C treatment, and Fast Track Designation for IB1001 by the FDA for NPC. Recently, IntraBio announced positive pivotal trial results of IB1001 for Niemann-Pick disease type C treatment, and the drug met the primary endpoint, demonstrating improvement in symptoms, functioning, quality of life, and cognition in both pediatric and adult patients with NPC.

• #23 Advancements in Niemann-Pick Disease Type C Treatments

  https://www.delveinsight.com/blog/niemann-pick-disease-type-c-treatment

  Arimoclomol is being developed by Zevra Therapeutics, is an orally-delivered, first-in-class investigational product candidate for NPC. […] AZ-3102 is being developed by Azafaros for the treatment of NPC. It is an orally available azasugar with a unique dual mode of action, developed as a potential treatment for rare lysosomal storage disorders with neurological involvement. […] Before the approval of ZAVESCA, only symptomatic therapies were used for the treatment of neurological manifestations, psychiatric manifestations, and visceral manifestations associated with NPC. There are several Niemann-Pick Disease Type C clinical trials currently taking place investigating new therapeutic options for patients with NPC. […] The continued investment in research and development in this field is likely to shape a more robust and comprehensive Niemann-Pick Disease Type C treatment market.

• #24 Cyclo Therapeutics logs efficacy win in pivotal Niemann-Pick disease trial – Clinical Trials Arena

  https://www.clinicaltrialsarena.com/news/cyclo-therapeutics-logs-efficacy-win-in-pivotal-niemann-pick-disease-trial/

  Cyclo Therapeutics Trappsol Cyclo was able to induce clinical improvement in seven out of eight children with Neimann-Pick disease. […] A Phase III study examining a treatment for the rare genetic disorder Niemann-Pick disease has seen 87% of its participants, all younger than three years old, show signs of stabilisation or improvement. […] Results from a sub-study arm within the trial saw 87% who had reached the 24-week mark display signs of clinical improvement as measured by the Clinical Global ImpressionChange (CGI-C) Scale. Additionally, six out of seven patients who continued onto week 48 showed continued improvement. […] Dr Ronen Spiegel, trial investigator and director for the Center of Rare Disease at Emek Medical Center, said: The preliminary findings from the TransportNPC sub-study are encouraging and further underscore the potential of Trappsol Cyclo to address the significant unmet medical need in the treatment of NPC.

• #25 New drug slows Niemann–Pick disease | Nature Reviews Neurology

  https://www.nature.com/articles/nrneurol.2017.124

  A clinical trial has highlighted a promising new treatment for NiemannPick disease, type C (NPC1), a life-threatening lysosomal storage disorder that often commences in childhood. Researchers found that a preparation of 2-hydroxypropyl–cyclodextrin (HPCD) known as VTS-270 slowed the development of neurological symptoms in patients with this disorder. […] No FDA-approved therapies currently exist for NPC1. However, preclinical studies in mouse and cat models showed that HPCD a molecule that can bind and solubilize hydrophobic molecules such as cholesterol slowed disease progression and prolonged lifespan.

• #26 Gene therapy shows promise for treating Niemann-Pick disease type C1

  https://www.genome.gov/news/news-release/Gene-therapy-shows-promise-for-treating-Niemann-Pick-disease-type-C1

  For the first time, National Institutes of Health (NIH) researchers have demonstrated in mice that gene therapy may be the best method for correcting the single faulty gene that causes Niemann-Pick disease, type C1 (NPC1). […] The researchers’ goal was to correct the faulty NPC1 gene in as many cells and organs as possible, with a strong focus on the brain. […] With a single injection, mice showed improvements in motor coordination, weight gain and longevity compared to those without this gene therapy. […] „The gene therapy is treating the root of the problem, the defective gene.” […] „For NPC1 patients, gene therapy could halt progression of the disease, improve the quality of their lives and, hopefully, increase the patient’s life span.” […] The researchers work on gene therapy for NPC1 also has the potential to treat genetic disorders with some similar features.

• #27 Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice | bioRxiv

  https://www.biorxiv.org/content/10.1101/2024.06.07.597901v1.full-text

  Niemann-Pick disease, type C1 (NPC1) is a rare, fatal neurodegenerative disorder caused by pathological variants in NPC1, which encodes a lysosomal cholesterol transport protein. There are no FDA approved treatments for this disorder. […] Both systemic and central nervous system delivery of AAV9-hNPC1 have shown significant disease amelioration in NPC1 murine models. […] Higher vector doses and treatment earlier in life were associated with enhanced transduction in the nervous system and resulted in significantly increased lifespan. […] Our findings help define dose ranges, treatment ages, and efficacy in severe and hypomorphic models of NPC1 deficiency and suggest that earlier delivery of AAV9-hNPC1 in a pre-symptomatic disease state is likely to yield optimal outcomes in individuals with NPC1.

• #28 Niemann-Pick Disease Type C Gene Therapy Gets Rare Pediatric Disease Designation

  https://www.cgtlive.com/view/niemann-pick-disease-type-c-gene-therapy-rare-pediatric-disease-designation

  BGT-NPC, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Niemann-Pick disease type C (NPC), has received rare pediatric disease designation from the FDA. […] BGT-NPC utilizes an AAV9 vector and is intended to be injected into the cerebrospinal fluid as a 1-time treatment in order to provide a functional copy of NPC1, the disease-targeted gene. […] We are pleased to announce the publication of our work leading to the identification of a novel, minimal NPC1 promoter used in BGT-NPC, demonstrating the significant therapeutic potential of brain-targeted AAV-mediated gene therapy for the treatment of NPC1.

• #29 Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice | bioRxiv

  https://www.biorxiv.org/content/10.1101/2024.06.07.597901v1.full-text

  Gene therapy can provide the replacement of the dysfunctional NPC1 protein to treat the disease. […] We and others have previously demonstrated AAV9 vectors can effectively improve survival and delay NPC1 disease progression in a severe NPC1 murine model (Npc1m1N). […] Both direct CNS administration (intracerebroventricular or intracisternal magna) and systemic administration (retro-orbital or intracardiac) have successfully ameliorated disease in these mice. […] In our previous work, AAV9 vectors were administered at pre-symptomatic, weaning age (4 weeks old), but the question has remained of whether late(r) intervention can still be effective following early or post-symptomatic diagnoses in individuals. […] We show that survival is correlated with cerebral hNPC1 gene copy number following earlier intervention, highlighting the importance of early treatment to ameliorate disease progression.

• #30 Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice | bioRxiv

  https://www.biorxiv.org/content/10.1101/2024.06.07.597901v1.full-text

  Importantly, Npc1I1061T mice are more representative of corresponding human condition as NPC1 p.I1061T encodes a misfolded protein targeted for ERAD. […] The success of treatment in both mouse models highlights the immediate translational potential of this vector, and presents opportunities for further investigation, including examination of other routes of delivery, ages of administration, efficacy in larger animal models, and even combination with other therapeutic agents to potentially increase efficacy. […] In aggregate, our studies demonstrate that systemic delivery of AAV9-EF1a(s)-hNPC1 can have significant impact on NPC1 disease phenotype and improve survival in severe and milder mouse models of the disorder.

• #31 Current advancements in therapy for Niemann-Pick disease: progress and pitfalls – PubMed

  https://pubmed.ncbi.nlm.nih.gov/37211769/

  Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, lysosomal storage disorder. To combat the progressive neurodegeneration in NPC, disease-modifying treatment needs to be introduced early in the course of the disease. The only approved, disease-modifying treatment is a substrate-reduction treatment, miglustat. Given miglustat’s limited efficacy, new compounds are under development, including gene therapy; however, many are still far from clinical use. […] Here, we offer an expert review of these therapeutic candidates, with a broad scope not only on the main pharmacotherapies, but also on experimental approaches, gene therapies, and symptomatic strategies. […] We conclude a combination of treatment strategies should be sought, with a holistic approach, to improve the quality of life of affected individuals and their families.

• #32

  https://link.springer.com/article/10.1007/s11011-021-00842-0

  Arimoclomol is currently undergoing clinical trials to assess efficacy in the treatment of various neurodegenerative diseases. […] The complexity of NPC disease has led to many different therapeutic attitudes. […] In summary, the treatment efforts applied in NPC were focused on i) decreasing the quantity of intra lysosomal free cholesterol, ii) reducing the synthesis of glucosylceramide by inhibiting the activity of its synthase, iii) restriction of inflammatory processes and immune system response, iv) strengthening the efflux of free cholesterol from the lysosomal compartment into cytosol, v) influencing the expression of genes needed to induce cell differentiation by inhibiting histone deacetylases (HDAC), vi) action of pharmacological chaperones to stimulate cellular protein repair pathway by activation of molecular chaperones such as heat shock proteins, vii) the development of gene therapy. […] The research for effective treatment of NPC is still ongoing.

• #33 Combination therapy a potential strategy for treating Niemann-Pick disease | Whitehead Institute

  https://wi.mit.edu/news/combination-therapy-potential-strategy-treating-niemann-pick-disease

  Niemann-Pick disease is caused by defects in autophagy that allow cholesterol to build up in liver and neuronal cells. […] Although there is currently no effective treatment for NPC disease, a clinical trial examining potential cholesterol-lowering effects of the drug cyclodextrin in NPC patients is ongoing. […] But when they use it at a lower dose in combination with another small molecule, carbamazepine, which stimulates autophagy, then it significantly improves the survival of the cells. Such an approach lowers cholesterol levels and restores the autophagy defects at the same time. This could be a new type of treatment for NPC disease. […] When this drug, carbamazepine, which is a mood stabilizer prescribed for bipolar disorder, was added in combination with low doses of cyclodextrin, both cholesterol accumulation and autophagy defects were rescued in the NPC-mutated cells. […] From here, this combination of drugs should be tested in animal models to see if it has a beneficial effect, says Maetzel.

• #34 Niemann-Pick disease type C: testing a potential new drug treatment | Action Medical Research

  https://action.org.uk/research/niemann-pick-disease-type-c-testing-potential-new-drug-treatment

  The results of our laboratory experiments are encouraging suggesting that an existing drug could help boost the effectiveness of drug treatment for children with Niemann-Pick disease type C, says Professor Frances Platt of the University of Oxford. […] Since this drug is already used in the clinic, it could rapidly be repurposed for treating this condition helping to reduce the impact of this life-limiting disease on children and their families. […] Professor Platt investigated whether a drug (fingolimod, FTY720) that is already used to treat multiple sclerosis might also provide benefits for NPC. […] We found that using FTY720 alone helped to improve certain neurological symptoms in our laboratory model enhancing mobility and reducing clumsiness and tremors, says Professor Platt. […] But we had even better results by combining this drug with miglustat helping to extend lifespan compared with using either drug alone.

• #35 Niemann-Pick disease type C: testing a potential new drug treatment | Action Medical Research

  https://action.org.uk/research/niemann-pick-disease-type-c-testing-potential-new-drug-treatment

  The researchers are now working towards confirming these results before moving towards a potential clinical trial of this drug combination in the future. […] We hope this drug treatment will ultimately be proven to help improve symptoms and lengthen the lives of children with this devastating condition, says Professor Platt. […] We are aiming to repurpose an existing drug that is already used to treat multiple sclerosis to develop a much-needed new treatment for NPC patients, says Professor Platt. […] We hope that using both drugs together could prove a powerful combination, particularly because they each target different biological processes involved in the disease, says Professor Platt. […] Should their results look promising, the researchers hope to move quickly into clinical trials involving patients with NPC.

• #36 Advancing diagnosis and treatment of Niemann-Pick C disease through biomarker discovery

  https://www.explorationpub.com/Journals/ent/Article/100412

  Niemann-Pick C disease is a rare neurodegenerative, lysosomal storage disease caused by accumulation of unesterified cholesterol. […] At present drug treatment options for NPC are limited. The only approved drug for treatment of NPC is the glycosphingolipid synthesis inhibitor miglustat (approved in the EU and 40 countries worldwide but not the US). […] The disappointing regulatory outcomes for the recent Phase 2b/3 trials for arimoclomol and for 2-hydroxypropyl–cyclodextrin underscore the challenges in conducting an interventional clinical trial for this disorder. […] For this reason, it would be highly desirable to use reliable, non-invasive biomarkers to assess response to interventions. […] Plasma C-triol, TCG, and PPCS biomarkers have been shown to be useful, but limited, tools for monitoring treatment responses in NPC1 patients.

• #37 Advancing diagnosis and treatment of Niemann-Pick C disease through biomarker discovery

  https://www.explorationpub.com/Journals/ent/Article/100412

  However, in the Phase 1/2 trial of intrathecal HPCD, neither plasma nor CSF levels correlated with the demonstrated clinical benefit in slowing neurodegeneration. […] By contrast, there is increasing evidence that proteomic rather than metabolomic biomarkers may be better suited to monitoring CNS treatment efficacy. […] The discovery of NPC-specific blood-based biomarkers and their rapid dissemination over the past decade into clinical laboratories have transformed the approach to disease diagnosis. […] Finally, the drug development landscape for NPC remains challenging. At present, the field lacks a validated, non-invasive biomarker to monitor the course of disease and CNS response to therapy. Thus, there is an urgent need for new biomarkers that could serve as surrogate endpoints to accelerate drug approval.

• #38 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  The treatment landscape for Niemann-Pick Disease Type C (NPC) is undergoing a significant transformation, with traditional symptom management approaches increasingly giving way to more targeted and disease-modifying therapies. […] Emerging therapies, such as substrate reduction therapy (SRT), chaperone therapies, and investigational gene therapies, are offering more personalized and effective solutions aimed at slowing disease progression and improving neurological and systemic outcomes. […] This debilitating trajectory underscores the critical and urgent need for therapies that go beyond simply managing symptoms and actively modify the course of this devastating disease. […] Advanced treatments like gene therapy, substrate reduction therapy (SRT), and chaperone therapies can be tailored with this granular perspective to maximize their efficacy and reduce any potential side effects.

• #39 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  The treatment landscape for Niemann-Pick Disease Type C (NPC) is witnessing significant innovation due to extensive research and development activities by leading pharmaceutical companies. […] Given the progress toward personalized and precision medicine strategies, tailoring therapies according to patients’ genetic profiles as well as a history of disease progression increasingly assumes importance. […] In September 2024, The U.S. Food and Drug Administration approved Miplyffa (arimoclomol), an oral therapy for the treatment of Niemann-Pick Disease Type C (NPC). […] The Niemann-Pick Disease Type C (NPC) treatment market is rapidly evolving, fuelled by innovative therapies and a growing emphasis on personalized medicine. […] This growth is primarily attributed to a departure from conventional treatments and a focus on targeted approaches like substrate reduction therapies (SRT), chaperone therapies, and gene therapies.

• #40 Niemann-Pick Disease Type C Market Expected to Exhibit a CAGR of 17.05% During 2025-2035, Impelled by Rising Awareness and Early Diagnosis – BioSpace

  https://www.biospace.com/press-releases/niemann-pick-disease-type-c-market-expected-to-exhibit-a-cagr-of-17-05-during-2025-2035-impelled-by-rising-awareness-and-early-diagnosis

  This transformation in NPC management underscores a commitment to individualized treatment strategies, where while therapies like hydroxypropyl-beta-cyclodextrin (HPCD) have demonstrated value, newer avenues such as gene therapy and neuroprotective agents are offering options for patients with severe or rapidly progressing disease.

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