- Email: [email protected]
G.P.97
824
Abstracts / Neuromuscular Disorders 24 (2014) 791–924
determine the correction of TA physiology at this dose are underway. Similarly, dose ranging experiments using IV tail vein injections with 5 doses (N = 3 per dose) ranging from 1 1012 to 1 1014 vg/kg are underway, and results of both protein expression and physiology studies will be presented. Our results show that U7snRNA-mediated exon skipping in Dup2 is both titratable and highly efficient. The establishment of a IV MED for this vector will allow planning of INDenabling GLP toxicology studies.
http://dx.doi:10.1016/j.nmd.2014.06.110
DMD 2 THERAPEUTIC EVALUATIONS AND APPROACHES G.P.97 Prophylactic oral bisphosphonate therapy in Duchenne muscular dystrophy: The Newcastle upon Tyne experience A. Sarkozy 1, R. Srinivasan 2, D. Rawlings 3, M. Guglieri 4, C. Owen 5, V. Straub 4, T. Cheetham 5, K. Bushby 4 1 Dubowitz Neuromuscular Centre, ICH Institute of Child Health and Great Ormond Street Hospital, London, UK; 2 University Hospital of North Tees, Stockton on Tees, UK; 3 Regional Medical Physics Department, Freeman Hospital, Newcastle upon Tyne, UK; 4 Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, UK; 5 Department of Paediatrics, Royal Victoria Infirmary, Newcastle upon Tyne, UK Duchenne muscular dystrophy (DMD) is an X-linked condition characterized by progressive muscle weakness. Glucocorticoids (GC) are a key pharmacological intervention that is associated with prolonged ambulation, reduction of scoliosis and better-preserved respiratory function. However long-term GC therapy, in particular daily regimens, is a significant risk factor for osteoporosis and vertebral fractures. While bisphosphonates (BP) are recommended in case of fractures, prophylactic use of BP remains controversial. Here we summarize our experience of prophylactic BP therapy on a group of DMD patients on daily GC on follow up at the paediatric neuromuscular clinic in Newcastle upon Tyne. Patients were offered prophylactic BP (oral Risedronate) under the guidance of the local paediatric endocrinology team from January 2008. Patients were reviewed 6 monthly for tolerability, side effects, bone pain, frequency of fractures and impact on bone mineral density (BMD) determined by yearly DXA analysis. Vitamin D supplementation (800–1000 IU/L daily) was provided and insufficiencies/deficiencies were treated. Out of a total of 52 patients included in this study, 9 stopped treatment because of side effects (in particular abdominal or joint pain and flu like symptoms). 43 boys continued BP therapy for an average of 24 months (range 12–54 months). Median lumbar spine adjusted BMD (BMAD) Z-scores remained stable during treatment, being 0.11 at baseline and 0.21 at the 3rd year follow up. Z-scores for total body mineral content (minus head) were stable during the period of treatment. 7 patients suffered long bone fracture during therapy and 3 had vertebral fractures (VF), the majority having been on GC for >36 months at the time of fracture. Patients who suffered VF all had lumbar spine BMAD Z-scores < 1 at baseline. In summary, our results indicate that prophylactic BPs therapy is well tolerated by most patients and may have a role in preventing steroid-induced osteoporosis in DMD.
http://dx.doi:10.1016/j.nmd.2014.06.111
G.P.98 Changes in height and age adjusted DXA bone indices with oral bisphosphonate treatment in Duchenne muscular dystrophy C. Tian 1, M. Rutter 1, L. Hornung 1, J. Khoury 1, L. Miller 2, J. Bange 1, I. Rybalsky 1, B. Wong 1 1 Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 2 University of Connecticut, Storrs, USA Osteoporosis is a major problem in Duchenne Muscular Dystrophy (DMD) due to long term glucocorticoid (GC) therapy and impaired mobility. There are currently no standard of care guidelines for detection or treatment of osteoporosis in DMD. There is limited data on bisphosphonate (BP) treatment of osteoporosis in pediatric DMD patients. This is the first study using height and age adjusted Z scores to assess changes in bone mineral density (BMD) and bone mineral content (BMC) in DMD boys treated with oral BP. To assess changes in bone mineral density (BMD) and bone mineral content (BMC) in DMD boys treated with oral BP. Retrospective study of total body (TB) and lumbar spine (LS) BMD and BMC by DXA in DMD boys treated with oral alendronate, studied between January 2005 and July 2012. Height- and age-adjusted Z-scores (HAZ) were derived. Paired t-tests were used to compare changes in BMD and BMC one year prior and one year post BP treatment. We studied 26 BP-treated DMD boys (mean age ± SD 10.9 ± 3.8 yrs and daily GC duration 3.3 ± 1.5 yrs at BP start). BP treatment duration at the end of the study period was 2.8 ± 1.1 yrs. Prior to starting BP, TB BMD and BMC-HAZ decreased progressively, while LS BMD and BMC-HAZ remained stable. Mean TB BMD and BMC-HAZ were 1.89 and 2.90 and mean LS BMD and BMC-HAZ were 0.89 and 1.07 at BP initiation. DXA bone indices stabilized or improved with BP treatment. There was significant improvement in LS BMD-HAZ (p < 0.0001) and BMC-HAZ (p < 0.0001), and TB BMC-HAZ (p = 0.0092) after one year of BP treatment. Oral BP treatment stabilized further decline of TB bone indices, and improved LS BMD and BMC HAZ and TB BMC HAZ. Our study suggests that oral BP may be beneficial for bone health in DMD boys. Further study to assess clinical correlation of changes in DXA bone indices is needed to evaluate efficacy of oral BP treatment for osteoporosis in DMD patients. http://dx.doi:10.1016/j.nmd.2014.06.112
G.P.99 The Wilmington Robotic Exoskeleton (WREX) improves upper extremity function in patients with Duchenne muscular dystrophy T. Estilow, A. Glanzman, J. Flickinger, K.M. Powers, A. Moll, L. Medne, G. Tennekoon, S.W. Yum Children’s Hospital of Philadelphia, Philadelphia, USA Non-ambulatory patients with Duchenne muscular dystrophy (DMD) have arm weakness limiting anti-gravity movement resulting in severe functional impairments. The Wilmington Robotic Exoskeleton (WREX), by employing a unique 4 bar link technology married with a variable linear elastic band power source, allows for 3 dimensional gravity reduced movement of the arms to enhance function for the completion of Activities of Daily Living (ADL). To establish the utility of WREX in patients with DMD, we report our experience from 2011 to 2014. Nine boys with DMD, aged 11–17y/o (median age 16y/o), were evaluated. Active range of motion (AROM) and functional task completion (self-feeding, drinking from a glass, access to face for grooming, manage eyeglasses, and access their environment, computer, cell phone, and other technology) were completed both with and without the WREX. AROM (without WREX/with WREX) was the following: shoulder flexion 0–30 degrees/45–100 degrees, shoulder abduction 0–30 degrees/45–100 degrees, and elbow flexion was 0–100
Abstracts / Neuromuscular Disorders 24 (2014) 791–924
determine the correction of TA physiology at this dose are underway. Similarly, dose ranging experiments using IV tail vein injections with 5 doses (N = 3 per dose) ranging from 1 1012 to 1 1014 vg/kg are underway, and results of both protein expression and physiology studies will be presented. Our results show that U7snRNA-mediated exon skipping in Dup2 is both titratable and highly efficient. The establishment of a IV MED for this vector will allow planning of INDenabling GLP toxicology studies.
http://dx.doi:10.1016/j.nmd.2014.06.110
DMD 2 THERAPEUTIC EVALUATIONS AND APPROACHES G.P.97 Prophylactic oral bisphosphonate therapy in Duchenne muscular dystrophy: The Newcastle upon Tyne experience A. Sarkozy 1, R. Srinivasan 2, D. Rawlings 3, M. Guglieri 4, C. Owen 5, V. Straub 4, T. Cheetham 5, K. Bushby 4 1 Dubowitz Neuromuscular Centre, ICH Institute of Child Health and Great Ormond Street Hospital, London, UK; 2 University Hospital of North Tees, Stockton on Tees, UK; 3 Regional Medical Physics Department, Freeman Hospital, Newcastle upon Tyne, UK; 4 Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, UK; 5 Department of Paediatrics, Royal Victoria Infirmary, Newcastle upon Tyne, UK Duchenne muscular dystrophy (DMD) is an X-linked condition characterized by progressive muscle weakness. Glucocorticoids (GC) are a key pharmacological intervention that is associated with prolonged ambulation, reduction of scoliosis and better-preserved respiratory function. However long-term GC therapy, in particular daily regimens, is a significant risk factor for osteoporosis and vertebral fractures. While bisphosphonates (BP) are recommended in case of fractures, prophylactic use of BP remains controversial. Here we summarize our experience of prophylactic BP therapy on a group of DMD patients on daily GC on follow up at the paediatric neuromuscular clinic in Newcastle upon Tyne. Patients were offered prophylactic BP (oral Risedronate) under the guidance of the local paediatric endocrinology team from January 2008. Patients were reviewed 6 monthly for tolerability, side effects, bone pain, frequency of fractures and impact on bone mineral density (BMD) determined by yearly DXA analysis. Vitamin D supplementation (800–1000 IU/L daily) was provided and insufficiencies/deficiencies were treated. Out of a total of 52 patients included in this study, 9 stopped treatment because of side effects (in particular abdominal or joint pain and flu like symptoms). 43 boys continued BP therapy for an average of 24 months (range 12–54 months). Median lumbar spine adjusted BMD (BMAD) Z-scores remained stable during treatment, being 0.11 at baseline and 0.21 at the 3rd year follow up. Z-scores for total body mineral content (minus head) were stable during the period of treatment. 7 patients suffered long bone fracture during therapy and 3 had vertebral fractures (VF), the majority having been on GC for >36 months at the time of fracture. Patients who suffered VF all had lumbar spine BMAD Z-scores < 1 at baseline. In summary, our results indicate that prophylactic BPs therapy is well tolerated by most patients and may have a role in preventing steroid-induced osteoporosis in DMD.
http://dx.doi:10.1016/j.nmd.2014.06.111
G.P.98 Changes in height and age adjusted DXA bone indices with oral bisphosphonate treatment in Duchenne muscular dystrophy C. Tian 1, M. Rutter 1, L. Hornung 1, J. Khoury 1, L. Miller 2, J. Bange 1, I. Rybalsky 1, B. Wong 1 1 Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 2 University of Connecticut, Storrs, USA Osteoporosis is a major problem in Duchenne Muscular Dystrophy (DMD) due to long term glucocorticoid (GC) therapy and impaired mobility. There are currently no standard of care guidelines for detection or treatment of osteoporosis in DMD. There is limited data on bisphosphonate (BP) treatment of osteoporosis in pediatric DMD patients. This is the first study using height and age adjusted Z scores to assess changes in bone mineral density (BMD) and bone mineral content (BMC) in DMD boys treated with oral BP. To assess changes in bone mineral density (BMD) and bone mineral content (BMC) in DMD boys treated with oral BP. Retrospective study of total body (TB) and lumbar spine (LS) BMD and BMC by DXA in DMD boys treated with oral alendronate, studied between January 2005 and July 2012. Height- and age-adjusted Z-scores (HAZ) were derived. Paired t-tests were used to compare changes in BMD and BMC one year prior and one year post BP treatment. We studied 26 BP-treated DMD boys (mean age ± SD 10.9 ± 3.8 yrs and daily GC duration 3.3 ± 1.5 yrs at BP start). BP treatment duration at the end of the study period was 2.8 ± 1.1 yrs. Prior to starting BP, TB BMD and BMC-HAZ decreased progressively, while LS BMD and BMC-HAZ remained stable. Mean TB BMD and BMC-HAZ were 1.89 and 2.90 and mean LS BMD and BMC-HAZ were 0.89 and 1.07 at BP initiation. DXA bone indices stabilized or improved with BP treatment. There was significant improvement in LS BMD-HAZ (p < 0.0001) and BMC-HAZ (p < 0.0001), and TB BMC-HAZ (p = 0.0092) after one year of BP treatment. Oral BP treatment stabilized further decline of TB bone indices, and improved LS BMD and BMC HAZ and TB BMC HAZ. Our study suggests that oral BP may be beneficial for bone health in DMD boys. Further study to assess clinical correlation of changes in DXA bone indices is needed to evaluate efficacy of oral BP treatment for osteoporosis in DMD patients. http://dx.doi:10.1016/j.nmd.2014.06.112
G.P.99 The Wilmington Robotic Exoskeleton (WREX) improves upper extremity function in patients with Duchenne muscular dystrophy T. Estilow, A. Glanzman, J. Flickinger, K.M. Powers, A. Moll, L. Medne, G. Tennekoon, S.W. Yum Children’s Hospital of Philadelphia, Philadelphia, USA Non-ambulatory patients with Duchenne muscular dystrophy (DMD) have arm weakness limiting anti-gravity movement resulting in severe functional impairments. The Wilmington Robotic Exoskeleton (WREX), by employing a unique 4 bar link technology married with a variable linear elastic band power source, allows for 3 dimensional gravity reduced movement of the arms to enhance function for the completion of Activities of Daily Living (ADL). To establish the utility of WREX in patients with DMD, we report our experience from 2011 to 2014. Nine boys with DMD, aged 11–17y/o (median age 16y/o), were evaluated. Active range of motion (AROM) and functional task completion (self-feeding, drinking from a glass, access to face for grooming, manage eyeglasses, and access their environment, computer, cell phone, and other technology) were completed both with and without the WREX. AROM (without WREX/with WREX) was the following: shoulder flexion 0–30 degrees/45–100 degrees, shoulder abduction 0–30 degrees/45–100 degrees, and elbow flexion was 0–100