Treating Niemann-Pick type C disease

There is no cure for Niemann-Pick type C disease (NP-C) and no universal NP-C management or treatment guidelines exist yet.^1,2 The future development and implementation of screening programs, validated assessment techniques and  treatment consensus guidelines are needed in order to optimize patient outcomes.

Management strategies include non-specific, symptomatic treatments and NP-C-specific therapies. Symptomatic therapies may be at least partially successful in treating some symptoms of NP-C but have no impact on disease progression or long-term outcomes (Table 1).^1,2

NP-C-specific therapies

Recent advances in the understanding of NP-C pathophysiology has led to the development of a new NP-C-specific treatment that has a direct impact on the course of the disease. Other NP-C-specific treatments are currently in development and will significantly improve the outlook for patients.

In January 2009, a glycosphingolipid synthesis inhibitor was approved in the European Union for the treatment of progressive neurological manifestations in adult and pediatric patients with NP-C. By inhibiting glucosylceramide synthase, this drug prevents the synthesis of glycosphingolipids and in doing so reduces the accumulation of these lipids in patients with NP-C. This glycosphingolipid synthesis inhibitor is the first treatment to be approved for patients with NP-C and has been proven to stabilize or slow down neurological disease progression in NP-C patients.³

Several other promising approaches to NP-C-specific therapy are under investigation, including cholesterol depletion therapy, cell-signalling target therapies, neurosteroid replacement therapy ^1,4 and sterol-binding agents.⁵

References

1. Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its potential treatment. UK Blackwell Publishing, 2007.
2. Patterson MC. Niemann-Pick disease Type C. Gene Reviews 2007a (updated 9 July). Accessible at: www.geneclinics.org. Accessed October 2008.
3. Patterson MC, Vecchio D, Prady H et al. Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet, Published online August 2 2007.
4. Patterson MC. A riddle wrapped in a mystery: understanding Niemann-Pick disease, type C. Neurologist 2003; 9: 301-10.
5. Liu B, Turley SD, Burns DK et al.  Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse. PNAS 2009; 106; 7: 2377-2382