Disease progression and outcome measures in spinobulbar muscular atrophy

2018 ◽  
Vol 84 (5) ◽  
pp. 754-765 ◽  
Author(s):  
Julia R. Dahlqvist ◽  
Freja Fornander ◽  
Josefine de Stricker Borch ◽  
Sofie T. Oestergaard ◽  
Nanna S. Poulsen ◽  
...  
Keyword(s):  
Disease Progression ◽  
Outcome Measures ◽  
Muscular Atrophy ◽  
Spinobulbar Muscular Atrophy

scholarly journals Treatment satisfaction in 5q-spinal muscular atrophy under nusinersen therapy

2021 ◽  
Vol 14 ◽  
pp. 175628642199890 ◽  
Author(s):  
Alma Osmanovic ◽  
Gresa Ranxha ◽  
Mareike Kumpe ◽  
Claudia D. Wurster ◽  
Benjamin Stolte ◽  
...  
Keyword(s):  
Side Effects ◽  
Spinal Muscular Atrophy ◽  
Outcome Measures ◽  
Treatment Satisfaction ◽  
Treatment Duration ◽  
Treatment Effectiveness ◽  
Muscular Atrophy ◽  
Patients Satisfaction ◽  
Motor Outcome ◽  
Ambulatory Patients

Background: Nusinersen was the first approved disease-modifying therapy for all 5q-spinal muscular atrophy (SMA) patients regardless of age or disease severity. Its efficacy in adults has recently been demonstrated in a large cohort by motor outcome measures, which were only partially suitable to detect changes in very mildly or severely affected patients. Patient-reported outcome measures (PROs) have been suggested as a valuable addition. Here, we aimed to assess treatment satisfaction and investigate whether it may be a useful PRO to monitor SMA patients. Methods: We enrolled 91 mainly adult 5q-SMA patients treated with nusinersen in a national, multicenter, cross-sectional observational study. 21 patients underwent longitudinal follow up. Patients’ satisfaction with treatment in four dimensions (global, effectiveness, convenience, side effects) was assessed by the Treatment Satisfaction Questionnaire for Medication German version 1.4 (TSQM-1.4©) and related to clinical parameters, motor scores, and treatment duration. Results: More than 90% of SMA patients were consistently satisfied over a median treatment duration of 10 months. Highest mean scores were observed in the dimensions ‘side effects,’ ‘global satisfaction,’ and ‘effectiveness’ (93.5 ± 14.8 versus 73.1 ± 21.0 and 64.8 ± 20.6, respectively). Patients’ satisfaction with the convenience of treatment was considerably lower (43.6 ± 20.2). Interestingly, satisfaction with the effectiveness was higher in ambulatory ( p = 0.014) compared with non-ambulatory patients and directly correlated to motor outcome measures. Five non-ambulatory patients withdrew from therapy. All of them presented with a deterioration of motor outcome measures and reported dissatisfaction with treatment effectiveness and convenience. Conclusion: Most patients were satisfied with nusinersen treatment effectiveness. Less severely affected patients indicated higher satisfaction. The TSQM-1.4© helped to identify therapy non-responders, who mainly addressed dissatisfaction with effectiveness and convenience. We suggest introducing the TSQM-1.4© as an additional PRO in SMA into clinical practice.

Disease progression in multiple sclerosis: combining physicians’ and patients’ perspectives?

2010 ◽  
Vol 17 (2) ◽  
pp. 234-240 ◽  
Author(s):  
JJ Kragt ◽  
JM Nielsen ◽  
FAH van der Linden ◽  
CH Polman ◽  
BMJ Uitdehaag
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcome ◽  
Disease Progression ◽  
Outcome Measures ◽  
Added Value ◽  
Impact Scale ◽  
Disability Status ◽  
The Impact ◽  
Nine Hole Peg Test ◽  
Combine Outcome

Background: To assess disease progression in multiple sclerosis (MS) several outcome measures are available. The interrelation of changes on different scales has not been studied extensively and the concept of combining scales has only recently been introduced in MS. Objective: To explore combining different clinical outcome measures in the evaluation of disease progression in MS. Methods: In 553 patients we studied the presence of relevant changes according to standard definitions on the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW) and the Multiple Sclerosis Impact Scale (MSIS-29). We examined ‘exclusive worsening’ (worsening on one measure while not worsening on any other measure) and ‘opposing changes’ (worsening on one measure while improving on another measure). Finally, we investigated the impact of combining assessments. Results: Based on the EDSS alone, 140 patients progressed. However, almost twice as many (275) showed worsening on any of the clinical outcome measures. Exclusive worsening was observed in 37 patients on the EDSS, 13 on the 9HPT, 39 on the T25FW and 44 on the MSIS physical. Of all worsened patients 76 (28%) showed opposing changes, a phenomenon predominantly observed when combining physician-based and patient-derived outcome measures. Conclusion: When assessing disease progression in MS, sensitivity to change can be increased by combining different outcome measures. The added value is especially present when combining measures from different perspectives. However, further research is needed to evaluate the optimal way to combine outcome measures before implementing this strategy in clinical studies.

scholarly journals Side chain to main chain hydrogen bonds stabilize a polyglutamine helix in the activation domain of a transcription factor

2018 ◽  
Author(s):  
Albert Escobedo ◽  
Busra Topal ◽  
Micha Ben Achim Kunze ◽  
Juan Aranda ◽  
Giulio Chiesa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Hydrogen Bonds ◽  
Transcriptional Activity ◽  
Main Chain ◽  
Muscular Atrophy ◽  
Helical Structure ◽  
Structural Basis ◽  
Tract Length ◽  
Spinobulbar Muscular Atrophy ◽  
Polyq Tract

Polyglutamine (polyQ) tracts are regions of low sequence complexity of variable length found in more than one hundred human proteins. These tracts are frequent in activation domains of transcription factors and their length often correlates with transcriptional activity. In addition, in nine proteins, tract elongation beyond specific thresholds causes polyQ disorders. To study the structural basis of the association between tract length, transcriptional activity and disease, here we addressed how the conformation of the polyQ tract of the androgen receptor (AR), a transcription factor associated with the polyQ disease spinobulbar muscular atrophy (SBMA), depends on its length. We found that the tract folds into a helical structure stabilized by unconventional hydrogen bonds between glutamine side chains and main chain carbonyl groups. These bonds are bifurcate with the conventional main chain to main chain hydrogen bonds stabilizing α-helices. In addition, since tract elongation provides additional interactions, the helicity of the polyQ tract directly correlates with its length. These findings suggest a plausible rationale for the association between polyQ tract length and AR transcriptional activity and have implications for establishing the mechanistic basis of SBMA.

scholarly journals The Use of Korean Medicine to Treat Patients with Spinobulbar Muscular Atrophy, Kennedy’s Disease - A Case Study

2017 ◽  
Vol 20 (1) ◽  
pp. 57-60
Author(s):  
Sungchul Kim ◽  
Seongjin Lee ◽  
Eunhye Cha ◽  
Jongcheol Lee ◽  
Jongdeok Lee ◽  
...  
Keyword(s):  
Muscular Atrophy ◽  
Korean Medicine ◽  
Spinobulbar Muscular Atrophy ◽  
Kennedy’S Disease ◽  
Kennedy's Disease

Laryngospasm: An underdiagnosed symptom of X-linked spinobulbar muscular atrophy

Neurology ◽  
2005 ◽  
Vol 64 (4) ◽  
pp. 753-754 ◽  
Author(s):  
A.-D. Sperfeld ◽  
C. O. Hanemann ◽  
A. C. Ludolph ◽  
J. Kassubek
Keyword(s):  
Muscular Atrophy ◽  
Spinobulbar Muscular Atrophy

scholarly journals Native Functions of the Androgen Receptor Are Essential to Pathogenesis in a Drosophila Model of Spinobulbar Muscular Atrophy

Neuron ◽  
2010 ◽  
Vol 67 (6) ◽  
pp. 936-952 ◽  
Author(s):  
Natalia B. Nedelsky ◽  
Maria Pennuto ◽  
Rebecca B. Smith ◽  
Isabella Palazzolo ◽  
Jennifer Moore ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Muscular Atrophy ◽  
Spinobulbar Muscular Atrophy ◽  
Drosophila Model

scholarly journals Assessment of Androgen Receptor Function in Genital Skin Fibroblasts Using a Recombinant Adenovirus to Deliver an Androgen-Responsive Reporter Gene1

1997 ◽  
Vol 82 (6) ◽  
pp. 1944-1948
Author(s):  
Michael J. McPhaul ◽  
Hans-Udo Schweikert ◽  
Diane R. Allman
Keyword(s):  
Androgen Receptor ◽  
Recombinant Adenovirus ◽  
Muscular Atrophy ◽  
Normal Subjects ◽  
Testicular Feminization ◽  
Spinobulbar Muscular Atrophy ◽  
Vitro Binding ◽  
The Family ◽  
Androgen Resistance

Abstract Mutations of the androgen receptor (AR) cause defects in virilization and can result in a spectrum of phenotypic abnormalities of male sexual development that includes patients with a completely female phenotype (complete testicular feminization) and individuals with less severe defects of virilization, such as Reifenstein syndrome. These phenotypes are not specific for mutations of the AR gene, however, and defects in other genes can also result in similar abnormalities of male development. For this reason, the diagnosis of an AR defect is laborious and requires data from endocrine studies, the family history, and in vitro binding experiments. To assist in the evaluation of patients with possible AR defects, we previously employed the use of a recombinant adenovirus to deliver an androgen-responsive gene into fibroblast cultures to assay AR function in normal subjects and patients with complete forms of androgen resistance. Although these studies demonstrated measurable differences between these two groups of subjects, we did not assay samples from patients with partial defects of androgen action. In the current study, we have modified this method to examine AR function in three groups of patients with known or suspected defects of AR function: patients with Reifenstein syndrome, patients with spinobulbar muscular atrophy, and patients with severe forms of isolated hypospadias. When assayed using this method, the AR function of patients with Reifenstein syndrome was intermediate between that of normal control subjects and that of patients with complete testicular feminization. Using the parameters established by the aforementioned experiments, we found that defective AR function can be detected in fibroblasts established from patients with spinobulbar muscular atrophy and in some patients with severe forms of isolated hypospadias, including two with a normal AR gene sequence. These results suggest that this method may have some utility in screening samples to detect defects of AR function, particularly when viewed in the context of other AR assays results.

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