Mucopolysaccharidosis I (MPS I) (Hurler Syndrome) – a lesser developed window

Mucopolysaccharidosis (MPS) is a group of rare, hereditary and incurable “storage diseases”, which is named after mucopolysaccharides (sugars bound to proteins). The stored mucopolysaccharides are called as glycosaminoglycans (GAGs).  GAGs are building blocks for bones, cartilage, tendons and many other tissues of the body. Normally the GAGs are catabolized with use of enzymes found in the lysosomes and eliminated from the body. Whereas in MPS the cycle breakdowns and each MPS disorder is caused by a deficiency in the activity of a single, specific lysosomal enzyme required for GAG degradation. As a result, the partially degraded GAGs are accumulated in the body within lysosomes and the elevation of GAG fragments in urine, blood and cerebral spinal fluid are commonly observed. This results in progressive cellular damage, which can affect multiple organ systems and lead to organ failure, cognitive impairment and reduced life expectancy. Skeletal and joint abnormalities are a prominent feature of many of the MPS disorders; patients often present with skeletal dysplasia, decreased joint mobility, short stature and CTS.

There are several types of MPS diseases such as MPS-I (Hurler syndrome), MPS II (Hunter syndrome), MPS III (Sanfilippo syndrome), MPS IV (Morquio syndrome), MPS VI (Maroteaux–Lamy syndrome), MPS VII (Sly syndrome) and others. Among all these MPS I is by far the most common form.

Hurler Syndrome is a rare disease with the prevalence of at 1/200,000 estimated in Europe in 2014. Incidence and prevalence of MPS calculated for United States in 2016 was found to be 1.2 per 100,000 live births and 1.8 per 1 million respectively. MPS I has the highest incidence and prevalence of 0.34 per 100,000 and 0.50 per 1,000,000.

The pipeline activity for Mucopolysaccharidosis I (MPS I) is little laidback with no developmental products in late stage (phase III). There are few products in the mid-stage developments. The early phase holds four products and a larger chunk of developmental molecules belongs to pre-clinical and discovery stage.

Few companies such as Jupiter Orphan Therapeutics, Magenta Therapeutics and ArmaGen are the key players for developing the potential candidates in phase II. JOT102 is being developed by Jupiter Orphan Therapeutics by its proprietary JOTROL platform technology. On the other hand, Magenta Therapeutics is developing MGTA-456 which is an allogeneic stem cell therapy. MGTA-456 has the potential to allow patients to be treated with higher cell doses than would otherwise be possible.

Valanafusp alfa, product of Armagen is a recipient of Fast-Track Designation, Rare Pediatric Disease Designation and Orphan Drug Designation by the United States Food and Drug Administration (USFDA). This novel investigational enzyme replacement therapy is under development by utilizing a proprietary “Trojan Horse” technology. The positive attributes of therapeutic candidate demonstrates a bright chance to reach the market.

The nominal pipeline activities emphasizes the prominent scope for more developments in the area. The intermittent pipeline activity offers the scope of development and a prompt chance of further enhancement to the early stage products. MPS disorders produce a wide variety of clinical presentations and therefore the diagnosis of this indication is often delayed, particularly in those patients without cognitive impairment. Considering the clinical heterogeneity and rarity of MPS, newborn screening may be the key to identifying individuals before the onset of irreversible clinical disease.

Vidhi Khosla

Associate Analyst