Enzyme replacement therapy for alpha‐mannosidosis: 12 months follow‐up of a single centre, randomised, multiple dose study

Abstract

These data suggest that rhLAMAN may be an encouraging new treatment for patients with alpha-mannosidosis.The study is designed to continue for a total of 18 months. Longer-term follow-up of patients in this study and the future placebo-controlled phase 3 trial are needed to provide greater support for the findings in this study.

Cognitive profile and activities of daily living: 35 patients with alpha‐mannosidosis

“…Data reported in this paper are based on baseline data in two randomised clinical trials studying the efficacy and safety of enzyme replacement therapy (ERT) with a recombinant human alpha-mannosidase for patients with AM (rhLAMAN-02 (EudraCT number: 2010-022084-36) and rhLAMAN-05 (EudraCT number: 2012-000979-17) (Borgwardt et al 2013). The baseline data of the cognitive function testing of 35 persons have been reviewed with special focus on visual function, reasoning, visuo-spatial skills, memory and attention.…”

“…Exclusion criteria were, among others, a known chromosomal abnormality or other syndromes affecting psychomotor development, history of bone marrow transplantation or psychosis within the previous 3 months (rhLAMAN-02) or current psychosis, also in remission (rhLAMAN-05) (Borgwardt et al 2013).…”

“…Intellectual and behavioural disabilities are typical signs in patients with alpha-mannosidosis (OMIM 248500) (AM). Other signs include hearing impairment, language disabilities, coarse facial features, skeletal deformities and motor function disturbances including abnormal balance, hypotonia and ataxia as well as muscular pain (Borgwardt et al 2013). The clinical spectrum of the disease is wide varying from mild to severe for each of the signs (Malm and Nilssen 2012).…”

Human recombinant lysosomal enzymes produced in microorganisms

“…Recombinant lysosomal α-mannosidase has been produced in CHO cells, tobacco plants, and P. pastoris [104][105][106][107]. Recently, results of 12 month follow-up of an ERT for α-mannosidosis using a recombinant enzyme produced in CHO cells showed improvements in somatic manifestations, and cerebral function and biomarkers [108]. Regarding the expression in microorganisms, α-mannosidase was expressed in P. pastoris obtaining a specific activity of 4 nmol min − 1 mg − 1 in the extracellular crude extract, and 287 nmol min − 1 mg − 1 after purification [107].…”

Chronic enzyme replacement therapy ameliorates neuropathology in alpha‐mannosidosis mice

“…However, immunological responses to the injected enzyme associated with high mortality precluded long‐term ERT of this mouse strain. To evaluate the chronic curative effect of enzyme application, we have generated an immune‐tolerant mouse model and studied the effect of high‐dose long‐term ERT on CNS pathology, using industrial produced rhLAMAN which is used to treat alpha‐mannosidosis patients in a phase I‐II clinical ERT trial 19. Strikingly, despite the low number of patients, a significant improvement of motor and to some extent also of cognitive function was observed.…”