What is Niemann-Pick Disease Type C?

Niemann-Pick Disease Type C (NPC) is a rare Lysosomal disorder characterized by the accumulation of cholesterol and other lipids in the lysosomes of various tissues, leading to progressive neurological deterioration. In NPC, there is problem that prevents the body from carrying lipids (cholesterol ) inside of cells. NPC is caused by mutations in the NPC1 and NPC2 gene.

Patients with Niemann-Pick disease Type C may experience the first symptoms of the disease at any age. NPC is characterized by its highly variable presentation, with symptoms ranging from subtle to severe and onset from infancy to adulthood. NPC affects multiple systems and is known for its significant neurological impact. 

How to diagnose?
Diagnosis involves clinical evaluation and genetic testing to confirm mutations in the NPC1 or NPC2 genes. Other diagnostic methods may include staining for cholesterol (filipin staining) to detect intracellular cholesterol accumulation and measuring derivatives of cholesterol in the blood (biomarker analysis).
 
What is the treatment?
While there is no cure for NPC, treatment is symptomatic and supportive, focusing on improving quality of life and prolonging survival.

Miglustat is approved in some countries to treat neurological symptoms. Therapies may include medications to manage symptoms such as cataplexy and seizures, physical therapy, and supportive care for feeding and respiratory issues.

Beta-Cyclodextrin and NPC
Beta-cyclodextrin (specifically, 2-hydroxypropyl-beta-cyclodextrin) has emerged as a potential therapeutic agent for NPC disease due to its ability to facilitate cholesterol removal from cells. Research has shown that beta-cyclodextrin can enhance the mobilization of cholesterol from lysosomes, the cellular compartments where it accumulates abnormally in NPC. This effect has the potential to alleviate some of the cellular dysfunction caused by lipid accumulation.

Clinical trials and studies have been conducted to evaluate the efficacy and safety of beta-cyclodextrin in NPC patients. While some results are promising, showing improvement in neurological function and a slowing of disease progression, the treatment is not without risks. Potential side effects, such as hearing loss and lung toxicity, have been observed, necessitating careful consideration and monitoring during therapy.

Ongoing research is focused on optimizing dosing, minimizing side effects, and understanding the long-term impacts of beta-cyclodextrin treatment in NPC patients. This therapeutic approach represents a significant step forward in the management of NPC, offering hope for improved outcomes in this challenging disease.

+1000 Estimated New Cases of NPC Worldwide and 30+ in the US Each Year

Symptoms
Neurological Manifestations: Progressive neurological deterioration including:
  • ataxia (difficulty coordinating movements)
  • dysarthria (difficulty speaking)
  • dysphagia (difficulty swallowing), along with seizures and tremors
  • cognitive decline
  • seizures
    Cataplexy (sudden, temporary loss of muscle tone and strength. Consciousness is maintained throughout the episode, which differentiates cataplexy from seizure
Systemic Features:
  • Hepatosplenomegaly (enlarged liver and spleen)
  • Jaundice in neonates
  • Respiratory difficulties due to aspiration
Psychiatric Symptoms: In adolescents and adults, psychiatric manifestations may be initial signs
  • Psychosis
  • Depression
  • Behavioral changes
Treatments

Oral Treatments for Type C