Hematopoietic stem cell transplantation for Morquio A syndrome

Abstract

Morquio A syndrome features systemic skeletal dysplasia. To date, there has been no curative therapy for this skeletal dysplasia. No systemic report on a long-term effect of hematopoietic stem cell transplantation (HSCT) for Morquio A has been described. We conducted HSCT for 4 cases with Morquio A (age at HSCT: 4–15 years, mean 10.5 years) and followed them at least 10 years (range 11–28 years; mean 19 years). Current age ranged between 25 and 36 years of age (mean 29.5 years). All cases had a successful full engraftment of allogeneic bone marrow transplantation without serious GVHD. Transplanted bone marrow derived from HLA-identical siblings (three cases) or HLA-identical unrelated donor. The levels of the enzyme activity in the recipient’s lymphocytes reached the levels of donors’ enzyme activities within two years after HSCT. For the successive over 10 years post-BMT, GALNS activity in lymphocytes was maintained at the same level as the donors. Except one case who had osteotomy in both legs one year later post BMT, other three cases had no orthopedic surgical intervention. All cases remained ambulatory, and three of them could walk over 400 m. Activity of daily living (ADL) in patients with HSCT was better than untreated patients. The patient who underwent HSCT at four years of age showed the best ADL score. In conclusion, the long-term study of HSCT has demonstrated therapeutic effect in amelioration of progression of the disease in respiratory function, ADL, and biochemical findings, suggesting that HSCT is a therapeutic option for patients with Morquio A.

Elosulfase alfa (BMN 110) for the treatment of mucopolysaccharidosis IVA (Morquio A Syndrome)

“…All cases remained ambulatory-3 patients could walk over 400 m and activities of daily living (ADL) for patients with HSCT were better than for untreated patients. A patient who underwent HSCT at 4 years of age showed the best ADL score [26]. The authors concluded that "the long-term study of HSCT has demonstrated therapeutic effect in slowing of progression of the disease in respiratory function, ADL, and biochemical findings, suggesting that HSCT is a therapeutic option for patients with Morquio A."…”

“…Hematopoietic stem cell transplantation (HSCT) has been tried in an effort to provide a source of normal enzyme for Morquio A patients and remains under investigation [19,20,25,26].…”

“…Additionally, as in other MPS disorders, HSCT has not been shown to effectively treat the severe skeletal manifestations of Morquio A [25]; this is likely due to lower vascularization of bone tissue. In a more recent paper by Yabe and colleagues, HSCT was shown to yield significant long-term improvements in quality of life (QOL) for Morquio A patients [26]. Investigators followed 4 patients for over 10 years after HSCT and reported that "the levels of the enzyme activity in the recipients' lymphocytes reached the levels of donors' enzyme activities within 2 years after HSCT.…”

Diagnosis of Morquio-A patients in Mexico: How far are we from prompt diagnosis?

“…International series describe a widespread amount of skeletal manifestations such as short trunk and neck, hip and knee dysplasia, spinal abnormalities, pigeon chest, among other less frequent characteristics (12,13). Early onset findings are kyphosis, scoliosis, growth retardation and altered gait (4,14).…”

Gene therapy for Mucopolysaccharidoses

“…Although ERT and HSCT have some advantages to slow progression of the disease for MPS, there are several limitations of ERT: i) requiring weekly injection, ii) short circulation of the drug in blood, iii) high cost, and iv) limited penetration to bone and CNS lesions [8–11]. HSCT is promising and far more cost-effective compared with ERT [12,13]; however, this cell-based therapy may not be applicable to all patients because of the limited availability of matched donors and the mortality risk of the procedure such as graft- versus -host disease (GVHD), infection disease, and additional complications [2–5,7,8,10,11]. Therefore, more effective and feasible therapy for MPS is urgently required.…”