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Biomedical subjects

M J Parton

Publications and source records attributed to M J Parton.

8 recordsLinked to original sources

No association of the SOD1 locus and disease susceptibility or phenotype in sporadic ALS.

Mutations in the copper zinc superoxide dismutase gene (SOD1) are found in 20% of familial and 3% of sporadic ALS patients. SOD1 protein aggregation can be detected in motor neurons of mutation-negative sporadic cases but a pathogenic role for wild-type SOD1 in ALS has not been demonstrated. In this study of 233 ALS cases and 248 controls the authors found no significant association between four individual single nucleotide polymorphisms and a deletion spanning the SOD1 locus (or their combined haplotypes), and disease susceptibility, or phenotype.

Amyotrophic Lateral Sclerosis↗

Prolonged survival in motor neuron disease: a descriptive study of the King's database 1990-2002.

Motor neuron disease is a clinically heterogeneous disease with significant differences in survival. The authors have characterised a subset of long term survivors seen in a tertiary clinic over a 12 year period in terms of clinical variables and demographics, comparing them with short term survivors and the remaining population. Thirty of 769 patients survived more than 10 years, corresponding to 4% of the total population. Significantly younger onset of disease symptoms and a predominance of pure upper motor neuron signs at presentation characterised the long term survivors, but factors traditionally regarded as being associated with poor prognosis were also well represented. For a few people with motor neuron disease there remains the hope, whatever the initial presentation, that their subsequent survival will be longer than expected.

Adult↗

Clinical trials in ALS: an overview.

Clinical trials in amyotrophic lateral sclerosis (ALS) have been conducted for over half a century now and have incorporated a wide variety of drugs. Most of these trials have had negative results and a cure remains elusive. The explosion in our understanding of molecular biology and parallel developments in clinical epidemiology have opened up a vast number of novel therapeutic strategies. However, advances in statistical analysis, computing, and global communications have also put greater pressure on scientific investigators to improve the design and implementation of clinical trials so that they permit rigorous testing of hypotheses within a solid ethical framework. This article documents the first published trial for all drugs tried clinically in the treatment of ALS, focusing in more detail on the large, multicenter trials of recent years, namely those involving riluzole, ciliary neurotrophic factor, insulin-like growth factor-I, brain-derived neurotrophic factor, and SR57746A. The problems in the design of trials in ALS are discussed, including the selection of end points and surrogate markers of disease progression, and the major parameters in ALS assessment are reviewed.

Amyotrophic Lateral Sclerosis↗

Detection of reverse transcriptase activity in the serum of patients with motor neurone disease.

The recognition that both human and murine retroviruses can cause motor neurone disease-like syndromes has raised the possibility that a retrovirus may be involved in the aetiology of motor neurone disease. This possibility was explored by looking for evidence of reverse transcriptase in the serum of motor neurone disease patients. Sera from 56 patients with motor neurone disease and 58 controls were tested by the product-enhanced reverse transcriptase assay, a technique that is approximately a million fold more sensitive than conventional reverse transcriptase assays and capable of detecting very low numbers of retroviral particles. Cell-free reverse transcriptase activity was detected in the serum of 33 of the 56 motor neurone disease patients (59%) but in only 3 of the controls (P < 0.00001). The reverse transcriptase activity was detectable in the presence of a large excess of an effective inhibitor of human cellular DNA polymerases and was therefore tentatively considered to be compatible with a retroviral origin. The reverse transcriptase activity, however, was not found to be due to the presence of known human exogenous retroviruses including HIV-1, HIV-2, HTLV-I, HTLV-II, HRV-5 or human foamy virus, as assessed by PCR-based assays. Further investigations will be required to determine the source of the reverse transcriptase activity observed in these motor neurone disease patient sera.

Adult↗