WHAT IS mucopolysaccharidosis (MPS)?
Mucopolysaccharidosis (MPS) is a group of rare genetic disorders characterized by a deficiency of lysosomal enzymes responsible for the normal degradation of glycosaminoglycans (GAGs) or mucopolysaccharides. The enzyme deficiency leads to progressive accumulation of GAGs in the lysosomes leading to the development of various somatic and neurologic symptoms. Only a few thousand patients worldwide are affected by any MPS subtype.
MPS is categorized into seven subtypes (I, II, III, IV, VI, VII and IX) based on the enzyme affected. Currently, patients are being treated with enzyme replacement therapies (ERT) whose efficacy is limited by poor distribution in the body. Therefore, ERT do not to address many clinical manifestations such as heart problems, stiff joints, spinal cord compression and visual impairment. In addition, ERT require weekly infusions in a hospital setting.
In MPS VI (Maroteaux-Lamy syndrome), which is the lead indication for odiparcil, the deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B; ASB) leads to the accumulation of dermatan sulfate and chondroitin sulfate. Patients present several clinical manifestations including a short stature, corneal clouding with visual impairment, hearing loss, dysostosis multiplex, hepatosplenomegaly, cardiac valve disease and reduced pulmonary function without intellectual deficit. As with other MPS subtypes, the time of onset, rate of progression and extent of the disease may vary between the affected individuals.
ODIPARCIL – OUR SOLUTION
Inventiva is developing odiparcil, a small orally available molecule with excellent distribution throughout the body and a good safety profile, for the treatment of several MPS subtypes.
Odiparcil’s ability to produce two forms of soluble GAGs (dermatan sulfates; chondroitin sulfates), which can be excreted via urine, makes it particularly suited to becoming the first GAG clearance therapy treating MPS I, II, IVA, VI and VII patients, where these types of GAGs accumulate.
Odiparcil is currently being tested in a Phase IIa clinical trial in adult MPS VI patients, the iMProveS trial. Headline results are expected in the second half of 2019. In addition, SAFE-KIDDS (SAFEty, pharmacoKInetics and pharmacoDynamics, Dose escalating Study), a Phase Ib study with odiparcil in pediatric population with MPS VI, is in preparation and due to start later in 2018.
HOW IS mucopolysaccharidosis (MPS) DIAGNOSED?
Most MPS patients are diagnosed as young children. Since MPS are rare diseases with only a few thousand patients worldwide for each subtype, family doctors may not be familiar with the disease and may initially not find the right diagnosis. New-born screening has only been implemented in very few countries and not for all MPS subtypes.
The doctor will initially test the patient’s urine for its GAG content. If elevated GAG levels are found, the doctor will measure enzyme activity in white blood cells or the skin and eventually confirm the diagnosis by testing the patient’s DNA for genetic changes. As MPS is an inherited disease, screening siblings of MPS patients may help diagnose affected children earlier than they would have been otherwise.
Patient associations can be found in almost all countries where people are effected by MPS. A reference to national MPS societies can be found on the website of the MPS Society (UK).