Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis
Objectives: Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder resulting from deficient lysosomal alpha-mannosidase activity. Clinical manifestations include progressive balance disorders, immune deficiency, skeletal abnormalities and cognitive deficits beginning in early ch...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-06-01
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| Series: | Molecular Genetics and Metabolism Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221442692030032X |
| _version_ | 1818203317935800320 |
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| author | Dawn Phillips Julia B. Hennermann Anna Tylki-Szymanska Line Borgwardt Mercedes Gil-Campos Nathalie Guffon Yasmina Amraoui Silvia Geraci Diego Ardigò Federica Cattaneo Allan M. Lund |
| author_facet | Dawn Phillips Julia B. Hennermann Anna Tylki-Szymanska Line Borgwardt Mercedes Gil-Campos Nathalie Guffon Yasmina Amraoui Silvia Geraci Diego Ardigò Federica Cattaneo Allan M. Lund |
| author_sort | Dawn Phillips |
| collection | DOAJ |
| description | Objectives: Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder resulting from deficient lysosomal alpha-mannosidase activity. Clinical manifestations include progressive balance disorders, immune deficiency, skeletal abnormalities and cognitive deficits beginning in early childhood. Enzyme replacement therapy with recombinant human alpha-mannosidase (velmanase alfa) is scheduled for clinical development in the US beginning in 2020 and has been approved in the EU for treatment of non-neurological manifestations in cases of mild to moderate disease. This study assessed effects of velmanase alfa on fine and gross motor proficiency in children and adults. Methods: Integrated Bruininks-Oseretsky (BOT-2) test of Motor Proficiency data from velmanase alfa clinical trials was stratified by age for 14 adults and 19 children treated for up to 4 years. Results: Patients showed global developmental delays at baseline. For the combined adult and pediatric group there was a statistically significant increase (improvement) in BOT-2 total point score of 13% (p = .035, 95% CI 1.0, 25.0) from baseline to last observation. When stratified by pediatric versus adult patients, there was improvement in BOT-2 total point score in patients <18 years (mean percent increase from baseline to last observation 23%) compared to adults (mean decrease of −0.7%). Subtest analysis of individual BOT-2 items captured some improvement following velmanase alfa treatment in pediatric patients. Conclusions: There was limited ability to assess the BOT-2 change responses in adults. Pediatric patients showed stability or improvement in scaled scores relative to healthy peers, indicating continued skill acquisition, which may increase independence and contribute to improved patient quality of life. |
| first_indexed | 2024-12-12T03:23:26Z |
| format | Article |
| id | doaj.art-42c0c4184ba14c41947932f1981d6d3c |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-12T03:23:26Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-42c0c4184ba14c41947932f1981d6d3c2022-12-22T00:40:06ZengElsevierMolecular Genetics and Metabolism Reports2214-42692020-06-0123Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosisDawn Phillips0Julia B. Hennermann1Anna Tylki-Szymanska2Line Borgwardt3Mercedes Gil-Campos4Nathalie Guffon5Yasmina Amraoui6Silvia Geraci7Diego Ardigò8Federica Cattaneo9Allan M. Lund10UNC Chapel Hill, Division of Physical Therapy, School of Medicine, Chapel Hill, NC, United States of America; Corresponding author at: 1104 Willow Drive, Chapel Hill, NC 27517, United States of America.University Medical Centre Mainz, Dept. Pediatric and Adolescent Medicine, Villa Metabolica, Mainz, GermanyDepartment of Paediatric, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, PolandCentre for Inherited Metabolic Diseases, Department of Paediatrics and Department of Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkMetabolism and Pediatric Research Unit, Reina Sofia University Hospital, IMIBIC, University of Cordoba, Unidad de Metabolismo e Investigación Pediátrica, Hospital Universitario Reina Sofía, Universidad de Córdoba, CIBERObn, Córdoba, SpainReference Center for Inherited Metabolic Diseases, Femme Mere Enfant Hospital, Lyon, FranceSphinCS GmbH, Clinical Science for LSD, Hochheim, GermanyChiesi Farmaceutici S.p.A, Parma, ItalyChiesi Farmaceutici S.p.A, Parma, ItalyChiesi Farmaceutici S.p.A, Parma, ItalyCentre for Inherited Metabolic Diseases, Department of Paediatrics and Department of Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkObjectives: Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder resulting from deficient lysosomal alpha-mannosidase activity. Clinical manifestations include progressive balance disorders, immune deficiency, skeletal abnormalities and cognitive deficits beginning in early childhood. Enzyme replacement therapy with recombinant human alpha-mannosidase (velmanase alfa) is scheduled for clinical development in the US beginning in 2020 and has been approved in the EU for treatment of non-neurological manifestations in cases of mild to moderate disease. This study assessed effects of velmanase alfa on fine and gross motor proficiency in children and adults. Methods: Integrated Bruininks-Oseretsky (BOT-2) test of Motor Proficiency data from velmanase alfa clinical trials was stratified by age for 14 adults and 19 children treated for up to 4 years. Results: Patients showed global developmental delays at baseline. For the combined adult and pediatric group there was a statistically significant increase (improvement) in BOT-2 total point score of 13% (p = .035, 95% CI 1.0, 25.0) from baseline to last observation. When stratified by pediatric versus adult patients, there was improvement in BOT-2 total point score in patients <18 years (mean percent increase from baseline to last observation 23%) compared to adults (mean decrease of −0.7%). Subtest analysis of individual BOT-2 items captured some improvement following velmanase alfa treatment in pediatric patients. Conclusions: There was limited ability to assess the BOT-2 change responses in adults. Pediatric patients showed stability or improvement in scaled scores relative to healthy peers, indicating continued skill acquisition, which may increase independence and contribute to improved patient quality of life.http://www.sciencedirect.com/science/article/pii/S221442692030032X |
| spellingShingle | Dawn Phillips Julia B. Hennermann Anna Tylki-Szymanska Line Borgwardt Mercedes Gil-Campos Nathalie Guffon Yasmina Amraoui Silvia Geraci Diego Ardigò Federica Cattaneo Allan M. Lund Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis Molecular Genetics and Metabolism Reports |
| title | Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis |
| title_full | Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis |
| title_fullStr | Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis |
| title_full_unstemmed | Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis |
| title_short | Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis |
| title_sort | use of the bruininks oseretsky test of motor proficiency bot 2 to assess efficacy of velmanase alfa as enzyme therapy for alpha mannosidosis |
| url | http://www.sciencedirect.com/science/article/pii/S221442692030032X |
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