GM2 gangliosidosis is a rare but devastating neurodegenerative disease which is caused by mutations in the GM2 gangliosidoses synthase-1 genes. The underlying cause is defective activity of the GM2 gangliosidase, a lysosomal cysteine beta-hexosaminidase that attacks terminal glucosamine residues of the GM2 ganglioside.
Achieving and maintaining a low disease burden is considered one of the most important considerations in assessing potential treatment for patients with GM2. Patients in a low disease burden are more likely to be able to achieve good functional and cognitive outcome with treatment.
The number of new cases of GMB2 was estimated to be approximately 1,700 for every 100,000 live births in the US during 1994. This is more than double the number estimated to occur globally. In the US, some new cases have been reported to have occurred in infants and children of all ethnicities. The cause of disease remains undetermined, although a strong association exists between GM2 and premature births and other fetal abnormalities. A recent report of one infant born with a missense mutation in the GM2 gene in Brazil (where the disease phenotype is also well established) suggests a more global prevalence than previously known.
Results from a recent clinical trial provides information that can be useful in clinical practice. The frequency of the findings related to the clinical signs of gangliosidosis, GM2 type was similar to that reported in previous reports from western European countries, suggesting a similar distribution and a similar etiology. However, the study does not show any evidence that the clinical signs of gangliosidoses are a reliable indicator of the presence of GM2 gangliosidosis. We cannot, however, exclude the possibility that the pattern of presentation in these countries is different from that observed in our region.
Findings from a recent study provides information about the mechanisms leading to accumulation of GM2 gangliosides in the brain during the preclinical disease period. A defect is probably present at about the 4th to 8th month. A similar process in sialidosis is suggested to occur in the kidneys, skeletal muscles and other organs.
When patients are asymptomatic and diagnosed by newborn screening, no specific treatment is required. However, if patients are symptomatic, a variety of treatments are available for lysosomal storage diseases, and some have a multidisciplinary support network.
Gangliosidoses, GM2 is a genetically heterogeneous lysosomal storage disorder, caused by a deficiency of the enzyme beta-hexosaminidase A. There is a wide variation in the clinical presentation, and there is a strong correlation between clinical severity and the enzyme assay value. Enzyme replacement therapy is the most recent treatment method applied in the therapy, but it was only introduced in the 1980s.
The safety data of Ib1001 does not necessarily imply safety of Ib1001 in combination with any other treatments. Ib1001-combinations are often described as a first line therapy in many conditions. The efficacy, however, does not change the safety profile. Further studies with Ib1001 alone would reveal safety profiles that deserve further scrutiny.
For members of families with GM2 gangliosidosis, our results suggest that, while there may be a significant environmental or genetic risk, the majority of cases (70%) occur randomly.
The primary cause of gm2 is most likely to be a mutation in the GM2 synthase gene. Although GM2-gangliosidosis was first reported in 1944 as a single case, it has a well-documented autosomal recessive mode of inheritance. The gene responsible for GM2-gangliosidosis has been mapped to chromosome 8q24 by linkage analysis, and a DNA test for GM2-gangliosidosis has been developed.
These data demonstrate the common safety profile of ib1001 and the possibility to expand its role in the treatment of patients suffering from diseases affecting the peripheral nervous system, like GM2-gangliosidoses.
Ib1001 is an effective and well-tolerated drug for patients with progressive neuropathic disease. Clinical trials of Ib1001 to treat neuropathic pain are ongoing and results have not yet been announced. However, Ib1001 has been administered to >400 patients in clinical trials. On the basis of the positive patient feedback and our own clinical experience, Ib1001 may be an alternative for patients who can tolerate the side effects of conventional drugs used to treat pain in progressive neuron degenerative diseases.