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Neuro-oncology Advances 2022Disseminated pediatric low-grade gliomas and glioneuronal tumors (dpLGG/GNTs) are associated with a poorer prognosis than nondisseminated pLGG/GNTs. To date there is no...
BACKGROUND
Disseminated pediatric low-grade gliomas and glioneuronal tumors (dpLGG/GNTs) are associated with a poorer prognosis than nondisseminated pLGG/GNTs. To date there is no comprehensive report characterizing the genome profile of dpLGG/GNTs and their relative survival. This systematic review aims to identify the pattern of genetic alterations and long-term outcomes described for dpLGG/GNT.
METHODS
A systematic review of the literature was performed to identify relevant articles. A quality and risk of bias assessment of articles was done using the GRADE framework and ROBINS-I tool, respectively.
RESULTS
Fifty studies published from 1994 to 2020 were included in this review with 366 cases reported. There was sporadic reporting of genetic alterations. The most common molecular alterations observed among subjects were 1p deletion (75%) and fusion (55%). BRAF p.V600E mutation was found in 7% of subjects. A higher proportion of subjects demonstrated primary dissemination compared to secondary dissemination (65% vs 25%). First-line chemotherapy consisted of an alkylation-based regimen and vinca alkaloids. Surgical intervention ranged from biopsy alone (59%) to surgical resection (41%) and CSF diversion (28%). Overall, 73% of cases were alive at last follow-up. Survival did not vary by tumor type or timing of dissemination. All studies reviewed either ranked low or moderate for both quality and risk of bias assessments.
CONCLUSIONS
Chromosome 1p deletion and fusion were the most common alterations identified in dpLGG/GNT cases reviewed. The relative molecular heterogeneity between DLGG and DLGNT, however, deserves further exploration and ultimately correlation with their biologic behavior to better understand the pathogenesis of dpLGG/GNT.
PubMed: 36382112
DOI: 10.1093/noajnl/vdac122 -
Orphanet Journal of Rare Diseases Jun 2023CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain... (Review)
Review
CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP.We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis - Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications.In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.
Topics: Humans; Neuroglia; Leukoencephalopathies; Brain; Mutation; Nervous System Malformations; Atrophy
PubMed: 37349768
DOI: 10.1186/s13023-023-02772-9 -
Medicine Jul 2019Researchers have evaluated the associations between mitochondrial DNA (mtDNA) 4977 bp deletion and presbycusis. This study aimed to assess the differences of mtDNA... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Researchers have evaluated the associations between mitochondrial DNA (mtDNA) 4977 bp deletion and presbycusis. This study aimed to assess the differences of mtDNA 4977 bp deletion between presbycusis patients and controls by conducting a meta-analysis of published studies.
METHODS
Databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched to collect case-control studies on the correlation between mitochondrial DNA 4977 bp deletion and presbycusis. The research findings of related articles were collected according to the inclusion criteria. Pooled odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated. Meanwhile, subgroup analysis was performed to examine the source of heterogeneity. Revman 5.3 and Stata 12.0 software were used for data synthesis.
RESULTS
Eight English and Chinese studies were included in the meta-analysis, the results of which showed that mitochondrial DNA 4977 bp deletion could increase the risk of presbycusis (OR = 8.16, 95% CI: 3.51-18.99), and the difference was statistically significant (P <. 01). Analysis of the polled OR showed the incidence of mtDNA 4977 bp deletion was 8.50 times higher in Asians with presbycusis than in the control group. And the OR in the studies of occidentals was 7.24. Sample source analysis was also performed with the sample source divided by temporal bone source and other sources (hair and blood). The OR was 4.18 and 22.36 for the temporal bone and other sources, respectively.
CONCLUSION
Mitochondrial DNA 4977 bp deletion could increase the risk of presbycusis.
Topics: Case-Control Studies; DNA, Mitochondrial; Humans; Presbycusis; Sequence Deletion
PubMed: 31277167
DOI: 10.1097/MD.0000000000016302 -
Journal of Oncology 2022To compare the efficacy of EGFR-TKIs combined with antiangiogenic agents between non-small cell lung cancer patients with exon 19 deletion and patients with exon 21...
Comparison of the Efficacy of EGFR-TKIs Combined with Antiangiogenic Agents between Patients with Exon 19 Deletion and Patients with Exon 21 Leu858 Arg Mutation: A Systematic Review and Meta-Analysis.
PURPOSE
To compare the efficacy of EGFR-TKIs combined with antiangiogenic agents between non-small cell lung cancer patients with exon 19 deletion and patients with exon 21 Leu858 Arg mutation.
METHODS
Electronic databases (PubMed, Embase, and the Cochrane Central Register of Controlled Trials) were systematically searched for studies published until March 2022. Randomized control trials comparing the survival of EGFR-TKIs plus antiangiogenic agents with EGFR-TKI were extracted. The primary endpoint was progression-free survival (PFS).
RESULTS
Five randomized control trials involving 1533 patients were as follows: 818 patients had exon 19 deletion, and 715 patients with exon 21 Leu858 Arg mutation. The methodological quality of the 5 randomized control trials was high. EGFR-TKIs plus antiangiogenic agents improved PFS in patients with exon 19 deletion (hazard ratio [HR] = 0.62, 95% confidence interval [CI]: 0.51-0.75) and exon 21 Leu858 Arg mutation (HR = 0.61, 95% CI: 0.50-0.75). PFS did not differ between the exon 19 deletion and exon 21 Leu858 Arg mutation groups ( = 0.07, =0.94).
CONCLUSIONS
PFS was comparable between patients receiving EGFR-TKIs combined with antiangiogenic agents with exon 19 deletion and those with exon 21 Leu858 Arg mutation.
PubMed: 36312218
DOI: 10.1155/2022/9399797 -
Malaria Journal Jan 2022The usefulness of histidine-rich protein-2/3 (HRP2/3)-based rapid diagnostic tests of malaria due to Plasmodium falciparum has been threatened by the appearance of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The usefulness of histidine-rich protein-2/3 (HRP2/3)-based rapid diagnostic tests of malaria due to Plasmodium falciparum has been threatened by the appearance of mutant PfHRP2/3 genes. This study was undertaken to determine the global pooled estimates of PfHRP2/3gene deletions.
METHODS
Relevant publications were identified from electronic databases such as; PubMed, EMBASE, and MEDLINE online. Besides, all the relevant literatures were retrieved through Google and Google Scholar. STATA software was used for data analysis. The pooled estimates were calculated using random effect model. The summary estimates were presented using forest plots and tables.
RESULTS
A total of 27 studies were included in the systematic review. However, only 24 and 17 studies were included for PfHRP2 and 3 gene deletion meta-analysis, respectively. The prevalence of PfHRP2 gene deletion across the individual studies ranged from the highest 100% to the lowest 0%. However, the meta-analysis result showed that the global pooled prevalence of PfHRP2 and PfHRP3 gene deletions were 21.30% and 34.50%, respectively. The pooled proportion of PfHRP2 gene deletion among false negative PfHRP2-based RDTs results was found to be 41.10%. The gene deletion status was higher in South America and followed by Africa. The pooled estimate of PfHRP2 gene deletion among studies, which did not follow the WHO PfHRP2/3 gene deletion analysis protocol was higher than their counter parts (21.3% vs 10.5%).
CONCLUSIONS
This review showed that there is a high pooled prevalence of PfHRP2/3 gene deletions in Plasmodium falciparum confirmed isolates and also a high proportion of their deletions among false-negative malaria cases using PfHRP2-based RDT results. Hence, malaria diagnosis based on PfHRP2-based rapid tests seems to be less sensitive and warrants further evaluation of PfHRP2/3 gene deletions.
Topics: Antigens, Protozoan; Gene Deletion; Humans; Malaria, Falciparum; Plasmodium falciparum; Prevalence; Protozoan Proteins
PubMed: 35093092
DOI: 10.1186/s12936-022-04051-7 -
BMC Medical Genetics Jan 2020Psoriasis is a multifactorial disorder, impacted by both genetic and environmental factors. Herein, a meta-analysis assessed the association of angiotensin-converting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psoriasis is a multifactorial disorder, impacted by both genetic and environmental factors. Herein, a meta-analysis assessed the association of angiotensin-converting enzyme gene insertion/deletion (ACE I/D) polymorphism and psoriasis susceptibility.
METHODS
A systematic search was used in databases of PubMed/Medline, Scopus, Web of Science, and Cochrane Library up to January 2019 without language restriction. A dichotomous analysis was carried out by RevMan 5.3 using crude odds ratio (OR) and 95% confidence interval (CI) to investigate the association between ACE I/D polymorphisms and the risk of psoriasis. A funnel plot analysis was used by CMA 2.0 to estimate a significant existence of publication bias.
RESULTS
Out of 61 studies retrieved from the databases, 16 studies were included in the meta-analysis. The pooled ORs for models of D vs. I, DD vs. II, ID vs. II, ID + DD vs. II, and DD vs. II + ID genotypes were 0.96 [95%CI: 0.82, 1.12; P = 0.58], 0.99 [95%CI, 0.73, 1.36; P = 0.96], 0.81 [95%CI, 0.72, 0.91; p: 0.0003], 0.91 [95%CI, 0.73, 1.13; P = 0.40], and 1.05 [95%CI, 0.85, 1.30; P = 0.68], respectively. A significant difference between ACE polymorphisms in patients with/without family history for the disease [OR = 1.44; 95%CI: 1.24, 1.67; P < 0.001] and also in patients mild/severe psoriasis [OR = 0.70; 95%CI: 0.55, 0.88; P = 0.002] was identified.
CONCLUSION
The results of the meta-analysis showed that ACE I/D polymorphism may be associated with psoriasis susceptibility, while ID genotype seemed to have a protective role in Caucasian patients affected by psoriatic arthritis and in studies with hospital-based controls.
Topics: Angiotensins; Genetic Predisposition to Disease; Genotype; Humans; INDEL Mutation; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Psoriasis; White People
PubMed: 31914957
DOI: 10.1186/s12881-019-0943-3 -
Child's Nervous System : ChNS :... Jul 2020The Pierre-Robin sequence (PRS) is a pattern of congenital facial abnormalities comprising micrognathia, glossoptosis, and airway obstruction. Associated spinal... (Review)
Review
INTRODUCTION
The Pierre-Robin sequence (PRS) is a pattern of congenital facial abnormalities comprising micrognathia, glossoptosis, and airway obstruction. Associated spinal pathologies have rarely been reported with PRS.
METHODS
We explore the molecular genetic basis of this association through a systematic review of spinal disease in patients with PRS. We also present an illustrative case of a PRS patient with tethered cord in the setting of chromosome 10q terminal deletion.
RESULTS
Our systematic literature review of spinal disease in patients with PRS revealed several patterns in the underlying genetic syndromes causing these conditions to co-occur. These principles are illustrated in the case of a 6-month-old female with PRS and a 14.34-Mb terminal deletion of chromosome 10q, who was found to have a sacral dimple during a routine outpatient checkup. Magnetic resonance imaging of the spine revealed a lumbar syrinx associated with tethered spinal cord. Surgical de-tethering was undertaken, with subsequent improvement in motor function and decrease in the size of the syrinx. The deletion of chromosome 10q in our patient had not previously been described in association with tethered cord or PRS.
CONCLUSION
Spinal pathologies are understudied contributors to disease burden in patients with PRS. The range of predisposing syndromes and mutations in patients with both PRS and spinal disorders remains poorly characterized but may be more defined than previously conceived. Clinical screening is most critical during neonatal and adolescent developmental periods with continued neurological assessment. This study emphasizes the need for early genetic testing and counseling in this patient population, in parallel with research efforts to develop molecular classifications to guide clinical management.
Topics: Adolescent; Airway Obstruction; Chromosome Deletion; Chromosomes, Human, Pair 10; Female; Humans; Infant; Infant, Newborn; Pierre Robin Syndrome; Spinal Diseases
PubMed: 32399800
DOI: 10.1007/s00381-020-04642-2 -
Cancer Cytopathology Feb 2022Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not... (Meta-Analysis)
Meta-Analysis Review
Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1-associated protein 1 (BAP1), methylthioadenosine (MTAP), 5-hydroxymethylcitosine (5-hmC), glucose transporter 1 (GLUT1), insulin like-growth factor II messenger RNA-binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta-analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy-one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval [CI], 0.59-0.71) and a specificity of 0.99 (CI, 0.93-1.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38-0.57) and 0.62 (CI, 0.53-0.71), respectively. BAP1 loss and CDKN2A HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78-0.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70-0.90) and 0.65 (CI, 0.41-0.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68-0.77) and a specificity of 0.90 (CI, 0.84-0.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and CDKN2A with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.
Topics: Biomarkers, Tumor; Glucose Transporter Type 1; Homozygote; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Sequence Deletion
PubMed: 34478240
DOI: 10.1002/cncy.22509 -
Amyotrophic Lateral Sclerosis &... Feb 2024Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by... (Review)
Review
OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by progressive muscle weakness, atrophy, and paralysis. The mutation-associated ALS has been classified as ALS6. We reported a case of ALS6 with de novo mutation and investigated retrospectively the characteristics of cases with mutation.
METHODS
We reported a male patient with a new heterozygous variant of the gene and comprehensively reviewed 173 ALS cases with mutation. The literature was reviewed from the PubMed MEDLINE electronic database (https://www.ncbi.nlm.nih.gov/pubmed) using "Amyotrophic Lateral Sclerosis and mutation" or " mutation" as key words from 1 January 2009 to 1 January 2022.
RESULTS
We report a case of ALS6 with a new mutation point (c.1225-1227delGGA) and comprehensively review 173 ALS cases with mutation. Though ALS6 is all with mutation, it is still a highly heterogenous subtype. The average onset age of ALS6 is 35.2 ± 1.3 years, which is much lower than the average onset age of ALS (60 years old). Juvenile FUS mutations have an aggressive progression of disease, with an average time from onset to death or tracheostomy of 18.2 ± 0.5 months. gene has the characteristics of early onset, faster progress, and shorter survival, especially in deletion mutation p.G504Wfs *12 and missense mutation of p.P525L.
CONCLUSIONS
ALS6 is a highly heterogenous subtype. Our study could allow clinicians to better understand the non-ALS typical symptoms, phenotypes, and pathophysiology of ALS6.
Topics: Humans; Male; Amyotrophic Lateral Sclerosis; Mutation; Mutation, Missense; Neurodegenerative Diseases; Retrospective Studies; RNA-Binding Protein FUS
PubMed: 37926865
DOI: 10.1080/21678421.2023.2272170 -
The Cochrane Database of Systematic... Jan 2020Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a (point) mutation in the second SMN1 allele. This results in degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. This is an update of a review first published in 2009 and previously updated in 2011.
OBJECTIVES
To evaluate if drug treatment is able to slow or arrest the disease progression of SMA types II and III, and to assess if such therapy can be given safely.
SEARCH METHODS
We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and ISI Web of Science conference proceedings in October 2018. In October 2018, we also searched two trials registries to identify unpublished trials.
SELECTION CRITERIA
We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a homozygous deletion or hemizygous deletion in combination with a point mutation in the second allele of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis. The primary outcome measure was change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full-time ventilation and adverse events attributable to treatment during the trial period. Treatment strategies involving SMN1-replacement with viral vectors are out of the scope of this review, but a summary is given in Appendix 1. Drug treatment for SMA type I is the topic of a separate Cochrane Review.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
The review authors found 10 randomised, placebo-controlled trials of treatments for SMA types II and III for inclusion in this review, with 717 participants. We added four of the trials at this update. The trials investigated creatine (55 participants), gabapentin (84 participants), hydroxyurea (57 participants), nusinersen (126 participants), olesoxime (165 participants), phenylbutyrate (107 participants), somatotropin (20 participants), thyrotropin-releasing hormone (TRH) (nine participants), valproic acid (33 participants), and combination therapy with valproic acid and acetyl-L-carnitine (ALC) (61 participants). Treatment duration was from three to 24 months. None of the studies investigated the same treatment and none was completely free of bias. All studies had adequate blinding, sequence generation and reporting of primary outcomes. Based on moderate-certainty evidence, intrathecal nusinersen improved motor function (disability) in children with SMA type II, with a 3.7-point improvement in the nusinersen group on the Hammersmith Functional Motor Scale Expanded (HFMSE; range of possible scores 0 to 66), compared to a 1.9-point decline on the HFMSE in the sham procedure group (P < 0.01; n = 126). On all motor function scales used, higher scores indicate better function. Based on moderate-certainty evidence from two studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: creatine (median change 1 higher, 95% confidence interval (CI) -1 to 2; on the Gross Motor Function Measure (GMFM), scale 0 to 264; n = 40); and combination therapy with valproic acid and carnitine (mean difference (MD) 0.64, 95% CI -1.1 to 2.38; on the Modified Hammersmith Functional Motor Scale (MHFMS), scale 0 to 40; n = 61). Based on low-certainty evidence from other single studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: gabapentin (median change 0 in the gabapentin group and -2 in the placebo group on the SMA Functional Rating Scale (SMAFRS), scale 0 to 50; n = 66); hydroxyurea (MD -1.88, 95% CI -3.89 to 0.13 on the GMFM, scale 0 to 264; n = 57), phenylbutyrate (MD -0.13, 95% CI -0.84 to 0.58 on the Hammersmith Functional Motor Scale (HFMS) scale 0 to 40; n = 90) and monotherapy of valproic acid (MD 0.06, 95% CI -1.32 to 1.44 on SMAFRS, scale 0 to 50; n = 31). Very low-certainty evidence suggested that the following interventions had little or no effect on motor function: olesoxime (MD 2, 95% -0.25 to 4.25 on the Motor Function Measure (MFM) D1 + D2, scale 0 to 75; n = 160) and somatotropin (median change at 3 months 0.25 higher, 95% CI -1 to 2.5 on the HFMSE, scale 0 to 66; n = 19). One small TRH trial did not report effects on motor function and the certainty of evidence for other outcomes from this trial were low or very low. Results of nine completed trials investigating 4-aminopyridine, acetyl-L-carnitine, CK-2127107, hydroxyurea, pyridostigmine, riluzole, RO6885247/RG7800, salbutamol and valproic acid were awaited and not available for analysis at the time of writing. Various trials and studies investigating treatment strategies other than nusinersen (e.g. SMN2-augmentation by small molecules), are currently ongoing.
AUTHORS' CONCLUSIONS
Nusinersen improves motor function in SMA type II, based on moderate-certainty evidence. Creatine, gabapentin, hydroxyurea, phenylbutyrate, valproic acid and the combination of valproic acid and ALC probably have no clinically important effect on motor function in SMA types II or III (or both) based on low-certainty evidence, and olesoxime and somatropin may also have little to no clinically important effect but evidence was of very low-certainty. One trial of TRH did not measure motor function.
Topics: Adolescent; Amines; Child; Child, Preschool; Creatine; Cyclohexanecarboxylic Acids; Humans; Hydroxyurea; Neuroprotective Agents; Randomized Controlled Trials as Topic; Spinal Muscular Atrophies of Childhood; Thyrotropin-Releasing Hormone; gamma-Aminobutyric Acid
PubMed: 32006461
DOI: 10.1002/14651858.CD006282.pub5