The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases

Abstract

The glycoprotein disorders are a group of lysosomal storage diseases (α-mannosidosis, aspartylglucosaminuria, β-mannosidosis, fucosidosis, galactosialidosis, sialidosis, mucolipidosis II, mucolipidosis III, and Schindler Disease) characterized by specific lysosomal enzyme defects and resultant buildup of undegraded glycoprotein substrates. This buildup causes a multitude of abnormalities in patients including skeletal dysplasia, inflammation, ocular abnormalities, liver and spleen enlargement, myoclonus, ataxia, psychomotor delay, and mild to severe neurodegeneration. Pharmacological treatment options exist through enzyme replacement therapy (ERT) for a few, but therapies for this group of disorders is largely lacking. Hematopoietic cell transplant (HCT) has been explored as a potential therapeutic option for many of these disorders, as HCT introduces functional enzyme-producing cells into the bone marrow and blood along with the engraftment of healthy donor cells in the central nervous system (presumably as brain macrophages or a type of microglial cell). The outcome of HCT varies widely by disease type. We report our institutional experience with HCT as well as a review of the literature to better understand HCT and outcomes for the glycoprotein disorders.

Fucosidosis—Clinical Manifestation, Long-Term Outcomes, and Genetic Profile—Review and Case Series

“…In a case of a symptomatic 3-year-old girl who underwent an umbilical cord blood (UCB) HSCT, a remarkable regression of neurological symptoms after HSCT was detected, cranial MRI results at two years post-HCT improved, a prior lactic acid peak disappeared on MRS, but no impact on dysostosis multiplex was observed [ 67 ]. Two out of three other patients showed decelerating of neurologic progress and a dramatic reduction in respiratory infections after HSCT [ 90 , 91 ]. Other HSCT-related trials were completed in 2008 [ 92 ].…”

“…It was confirmed that the enzyme was higher near the injection site (39–73% of normal) and lower in deep brain structures (2.6–5.5% of normal), but it reached all areas of the CNS. The direct CNS delivery of the enzyme was shown to be safe and in a follow-up study (in the same experiment) partial improvement in neuropathology following intracisternal ERT has been shown, implying that perhaps a more intensive ERT protocol is required to improve outcomes [ 91 , 93 ].…”

Mucolipidoses Overview: Past, Present, and Future

“…Despite the limitations, BMT did appear to point towards some beneficial effects on growth and intellectual development, although the mechanism remained unclear [ 111 ]. Naumchik et al described the role of hematopoietic cell transplants in several glycoproteins including ML (sialidosis, mucolipidosis II, mucolipidosis III) [ 112 ]. With the current understandings of HSCT, further modifications to the therapy are encouraged as well as the use of the therapy along with other different treatments.…”

Is hematopoietic stem cell transplantation a therapeutic option for mucolipidosis type II?

“…Hereby, metabolic “cross-correction” is achieved. Although the efficacy of HSCT has been explored in MLII [ [8] , [9] , [10] , [11] , [12] , [13] ], in-depth data are still scarce. This report summarizes the outcome of a 6.3-year-old MLII patient, who received HSCT at 9 months of age with the intention to preserve neurocognitive function.…”