A rare disease a day: Morquio syndrome

Day 4 of ‘a rare disease a day’ following on from Hunter syndrome, Gaucher disease and Tay-Sachs, it is the turn of Morquio syndrome (referred to as mucopolysaccharidosis IV or Morquio’s). This disease is an autosomal recessive lysosomal storage disease. There are two forms of Morquio syndrome: Type A and Type B. Type A –  do not have a or have a lower amount of an enzyme called N-acetylgalactosamine-6 sulfatase (GALNS) resulting in the accumulation of keratan sulfate. Type B do not produce enough of an enzyme called beta-galactosidase.

A patient with Morquio disease may display an array of symptoms such as: Abnormal heart development, Abnormal skeletal development, Hypermobile joints, Large fingers, Knock-knees, Widely spaced teeth, Bell-shaped chest (flared ribs), Compression of spinal cord, Enlarged heart, Dwarfism, Heart Murmur, below average height for certain age. And this is just for starters there are many other symptoms too. The severity of the disease can result in some patients living for 2 or 3 years or living upto 60 or 70 years.

As with so many of these rare (or perhaps ultra rare) diseases, parents of children with the disease have created dynamic foundations to raise funds for research and educate and support other families. Morquio disease has The Carol Ann Foundation which has created a registry of over 400 patients with Morquio A.

Treatment for Morquio A so far is focused on enzyme replacement therapy, BioMarin’s experimental drug for Morquio A syndrome is an enzyme replacement of GALNS called BMN 110 not to be confused with the recombinant human arylsulfatase B; galsulfase, Naglazyme®, also marketed by BioMarin Pharmaceutical Inc.  used and approved for MPS VI. BioMarin has multiple clinical trials underway for MPS IV. So far only one clinical study has completed. (UPDATE: ERT submitted but not yet FDA approved).

Small molecule chaperones have been the subject of research for Morquio B (and here, here , here , here ). Interestingly one of the earliest chaperones described  a galactose derivative, N-octyl-4-epi--valienamine (NOEV) which is relatively similar to miglustat (see image), which makes you wonder if that drug has been tested  for this disease (a quick search of PubMed for miglustat and morquio retrieves no hits). Chaperone therapy is only likely to be useful in 20-40% of patients.. The structure of GALNS was solved in 2012 which offers some insight for function of this and related enzymes. There has been relatively little research towards using gene therapy for Morquio A using adeno-associated virus (AAV)-based vectors, which carry human GALNS cDNA. It would seem there is plenty of scope for further research for type B.

morquio chaperone search

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