Niemann-Pick Disease Type A (NP-A) and Niemann-Pick Disease Type B (NP-B) were once thought to be separate diseases, but are now understood to be opposite ends of a spectrum of the same disease. They are both caused by a deficiency of the enzyme acid sphingomyelinase (ASM) and therefore are known as Acid Sphingomyelinase Deficiency (ASMD) Niemann-Pick disease. Many variations exist within this spectrum, in terms of clinical symptoms and rate of progression.
NP-B is a very rare inherited lysosomal storage disorder in which harmful quantities of a fatty substance called sphingomyelin build up in the body’s cells and organs. In NP-B this build up mainly occurs in the liver, spleen and lungs. Unlike NP-A, NP-B does not affect the brain and, although growth may be slow, those affected will survive into adulthood with many being able to lead a full and active life. A small number of patients may be described as having A/B variant, falling in the middle of the spectrum and exhibiting neurological problems which may become more apparent over time.
It is inherited when two copies of a faulty gene (a mutation) are passed on to a child. In every pregnancy of a couple who each carry a copy of the faulty Niemann-Pick gene, there is a 1 in 4 chance (25%) that their child will have Niemann-Pick disease. This is known as autosomal recessive inheritance.
The incidence of NP-B is estimated as 1 in 250,000 in the general population.
Niemann-Pick Disease Type B (NP-B) is caused by a severe deficiency of the enzyme acid sphingomyelinase. This is required to break down a fatty substance called sphingomyelin. Failure to break down sphingomyelin causes an accumulation and enlargement of the liver and spleen.
Niemann-Pick Disease Type B (NP-B) is diagnosed by measuring the level of the enzyme acid sphingomyelinase in the white blood cells. This can be done by testing a small blood sample. The diagnosis is usually confirmed by DNA sequencing to identify mutations.
The enzyme deficiency at the cause of NP-B arises from mutations in a gene on chromosome 11.
The first symptoms of Niemann-Pick Disease Type B (NP-B) are usually an enlarged liver and/or spleen in early childhood.
Symptoms can include:
There is usually no neurological involvement in NP-B. Most patients will survive into adulthood, but not without experiencing health problems.
There is currently no specific approved treatment, or cure, for Niemann-Pick Disease Type B (NP-B). However, patients will benefit from palliative treatments (individual medications that will help to treat the symptoms related to the condition). These improve the quality of life of patients who are experiencing symptoms.
There are clinical trials currently taking place investigating new therapeutic options for patients with NP-B.
Kim Stratton, Chief Executive Officer at Orphazyme, commented, “We are delighted with FDA’s decision to grant Breakthrough Therapy Designation to arimoclomol for NPC. Arimoclomol has been shown to have a clinically meaningful effect on disease progression in NPC that is further supported by a biomarker effect indicating an effect on the biological underpinnings of the disease and a favorable safety and tolerability profile. We are committed to bringing this product to patients as soon as possible. Breakthrough Therapy Designation is designed to expedite the development and review of products for serious diseases with the direct involvement of senior staff and we look forward to working closely with the FDA to further advance arimoclomol. Our preparations for filing in the US are underway and we are on track to submit a New Drug Application in H1 2020.”Read more