MPS I is mostly an irreversible progressive degenerative disease; however, some people are able to make a full recovery with an appropriate lifestyle and medication if diagnosed early enough before the onset of symptoms. At this time, there is no known cure for MPS I, but there have been several successful surgical procedures, medical treatments, and supportive care plans to help the patient live a full and active life. An intervention combining medication, surgery, therapeutic physical work, speech therapy, and massage is still being studied, but many patients are able to lead a full and normal life if treated in advance with medication and surgery. This has been done successfully at several universities, notably New York's Children's Hospital.
The signs of mucopolysaccharidoses can be variable and subtle. However, the signs are of great interest to the general practitioner because they can give valuable clues about the diagnosis to be made at a later stage. A careful history and examination helps to form an appropriate diagnosis and gives clues to the signs that can be noticed in particular individuals. In particular, ocular signs such as ptosis or strabismus are of special interest to the paediatric surgeon. The major symptom is usually progressive and requires extensive multidisciplinary care.
MPS is an incurable genetic disease involving accumulation of glycosphingolipids in the cell and in the extracellular space and is diagnosed based on symptoms, rather than a definite laboratory test. Children with MPS typically have symptoms with either a lethal or a late onset. There are four MPS diseases with different clinical features (Hurler, Scheie, Sanfilippo and Morquio A disease). MPS-II and MPS-III are often fatal in infancy due to pneumonia while MPS-IVA and MPS-IVB can be treated by splenectomy but have very variable outcomes.
MPS I can be as devastating as MPS II with an estimated 3.7 new cases per 2 million U.S. population per year. The lifetime risk of death in MPS I and MPS II is 7.9% and 19.4%, respectively, indicating that MPS I and MPS II are among the most common genetic disorders in the U.S. population.
Data from a recent study suggest that defects in glycosaminoglycan metabolism result in a syndrome more severe in the MPS II group and that a lack of expression of a mutant enzyme protein may be responsible for the disease. This may explain why there are no known correlations between the disease phenotype seen in MPS II patients and either a specific glycosaminoglycan defect or the presence of free-GAGs.
MPS I is treatable and manageable if symptomatic patients receive early intervention. Treatment strategies include enzyme replacement therapies, surgical intervention to decrease or eliminate brain damage, and therapies to suppress immune responses. MPS II and III are more serious, and many patients will need a combination of treatment approaches. MPS IV, which is non-neurological in its presentation, has been treated successfully with enzyme replacement and, in a few cases, gene therapy. Treatments that may be considered include hematopoietic stem-cell transplantation, organ transplantation, or stem-cell replacement therapy.
The development of ABO-102 has increased dramatically since its inception in the late 1980s. The major advance in ABO-102 in the past 5 years is the formulation of a more stable ABO-102-derived protein in a single dose formulation that is rapidly absorbed but very efficiently distributed. All the clinical parameters so far studied in conjunction with ABO-102 were well tolerated, demonstrating that further clinical trials should be pursued to determine whether a single-dose formulation would be more appropriately suited for clinical use. Further long-term safety and efficacy studies should be performed to evaluate the optimal dosage for a chronic infusion over the course of about 7 years.
The safety of abo-102 is not compromised in people with MPS I or II. In contrast to previous reports, abo-102 is well-tolerated in patients with MPS I and II.
Our cohort of patients confirms the results of randomized controlled trials and identifies patients likely to be eligible for enrollment in clinical trials and clinical studies. The majority of pediatric patients with MPS who do not qualify for inclusion in a clinical study are unable to complete these studies on patient and parental/provider request. Patients and clinicians should consider the potential benefits of enrollment in clinical trials and clinical studies.
Abo-102 is effective at reducing urinary GAL-derived MPS in patients with mucopolysaccharidoses. The improvement of quality of life for those with mucopolysaccharidoses should be considered as important benefits of this treatment.
In mucopolysaccharidoses type I and II, the primary defect and its underlying cause are the result of mutations at a distinct gene on chromosome 17. In mucopolysaccharidoses type III, the primary defect is the result of the abnormal function of the enzyme β-N-acetylglucosaminidase and the underlying cause is autosomal recessive inheritance of the mutated gene. In mucopolysaccharidoses type IV, there is no known cause. As with most genetic conditions, there is no cure for MPS. However, early diagnosis and appropriate treatment can greatly improve quality of life for individuals with mucopolysaccharidoses, which have no known cure.
Overall, all of the clinical trials so far indicated that ABO-102 has no detectable pharmacological activity. Although all patients receiving ABO-102 developed at least some level of clinical benefit, the trials to date demonstrated no differences between the two cohorts in terms of disease duration, overall survival, or quality of life.