Lysosomal storage disorders (LSD) are a heterogeneous group of about 50 metabolic rare diseases caused by an abnormal accumulation of toxic materials in the body’s cells as a result of enzyme deficiencies. Most lysosomal storage disorders are inherited, due to gene mutations, and currently there is no available treatment for many of them.
LSD may affect different parts of the body, including the skeleton, brain, skin or heart, and those affecting central nervous system, with high incidence in early childhood, are among the most severe.
Inborn errors of metabolism behind LSD cause the absence or deficiency of enzymes required to metabolize large molecules such as lipids, glycoproteins or mucopolysaccharides. Lysosomal storage diseases are generally classified by the accumulated substrate and include the sphingolipidoses (Farber Disease, GM1 and GM2 Gangliosidosis, Gaucher Disease…), oligosaccharidoses, mucolipidoses, mucopolysaccharidoses (Hunter Syndrome, Sanfilippo Syndrome, Morquio A and B…), lipoprotein storage disorders, lysosomal transport defects, neuronal ceroid lipofuscinoses and others.
Minoryx research in LSDs benefits from a grant of the Retos-Colaboración program 2016 (MINECO). [Know more]
Minoryx has developed a proprietary technological platform, Site-directed Enzyme Enhancement Therapy (SEE-Tx), to discover new pharmacological chaperones capable of restoring enzymatic functionality.
To validate the mechanism of action of the new compounds, the company has focused its research in GM1 Gangliosidosis and Morquio B, two diseases caused by the deficiency of the enzyme Beta-Galactosidase due to mutations in the GLB1 gene. This lysosomal enzyme cleaves galactose from different substrates, which in its absence are accumulated in GM1 patients.
GM1 Gangliosidosis has been classified into three major clinical types according to the age of onset and severity of symptoms: type I (infantile), type II (late infantile/juvenile) and type III (adult). The disease is estimated to occur approximately in 1 of every 100,000 or 200,000 live births.
Morquio B, also called Mucopolysaccharidosis IVB, is characterized by severe skeletal deformities and contrary to GM1, there is no neurological damage. Its incidence is around 1 of every 250,000 live births.
Nowadays around 160 mutations have been reported on the GLB1 gene causing either GM1 or Morquio B. About 70% are missense mutations which are suitable for Pharmacological Chaperone Therapy.