Dataset Information

Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS).

ABSTRACT: BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a progressive lethal disorder of large motor neurons of the spinal cord and brain. In approximately 20% of the familial and 2% of sporadic cases the disease is due to a defect in the gene encoding the cytosolic antioxidant enzyme Cu, Zn-superoxide dismutase (SOD1). The underlying molecular defect is known only in a very small portion of the remaining cases and therefore involvement of other genes is likely. As SOD1 receives copper, essential for its normal function, by the copper chaperone, CCS (Copper Chaperone for SOD), we considered CCS as a potential candidate gene for ALS. RESULTS:We have characterized the genomic organization of CCS and determined exon-intron boundaries. The 823 bp coding region of the CCS is organized in 8 exons. We have evaluated involvement of the CCS in ALS by sequencing the entire coding region for mutations in 20 sporadic ALS patients. CONCLUSIONS:No causative mutations for the ALS have been detected in the CCS gene in 20 sporadic ALS patients analyzed, but an intragenic single nucleotide polymorphism has been identified.

SUBMITTER: Silahtaroglu AN

PROVIDER: S-EPMC107843 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature

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Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS).

Silahtaroglu Asli N AN Brondum-Nielsen Karen K Gredal Ole O Werdelin Lene L Panas Marios M Petersen Michael B MB Tommerup Niels N Tümer Zeynep Z

BMC genetics 20020419

<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a progressive lethal disorder of large motor neurons of the spinal cord and brain. In approximately 20% of the familial and 2% of sporadic cases the disease is due to a defect in the gene encoding the cytosolic antioxidant enzyme Cu, Zn-superoxide dismutase (SOD1). The underlying molecular defect is known only in a very small portion of the remaining cases and therefore involvement of other genes is likely. As SOD1 receives copper, essent ...[more]

PMID: 11991808

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Project description:Thoughtful clinical trial design is critical for efficient therapeutic development, particularly in the field of amyotrophic lateral sclerosis (ALS), where trials often aim to detect modest treatment effects among a population with heterogeneous disease progression. Appropriate outcome measure selection is necessary for trials to provide decisive and informative results. Investigators must consider the outcome measure's reliability, responsiveness to detect change when change has actually occurred, clinical relevance, and psychometric performance. ALS clinical trials can also be performed more efficiently by utilizing statistical enrichment techniques. Innovations in ALS prediction models allow for selection of participants with less heterogeneity in disease progression rates without requiring a lead-in period, or participants can be stratified according to predicted progression. Statistical enrichment can reduce the needed sample size and improve study power, but investigators must find a balance between optimizing statistical efficiency and retaining generalizability of study findings to the broader ALS population. Additional progress is still needed for biomarker development and validation to confirm target engagement in ALS treatment trials. Selection of an appropriate biofluid biomarker depends on the treatment mechanism of interest, and biomarker studies should be incorporated into early phase trials. Inclusion of patients with ALS as advisors and advocates can strengthen clinical trial design and study retention, but more engagement efforts are needed to improve diversity and equity in ALS research studies. Another challenge for ALS therapeutic development is identifying ways to respect patient autonomy and improve access to experimental treatment, something that is strongly desired by many patients with ALS and ALS advocacy organizations. Expanded access programs that run concurrently to well-designed and adequately powered randomized controlled trials may provide an opportunity to broaden access to promising therapeutics without compromising scientific integrity or rushing regulatory approval of therapies without adequate proof of efficacy.

Dataset Information

Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS).

Publications

Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS).

Similar Datasets

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