Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preclinical data indicate that the administration of the amino acid L-threonine increases glycine levels in rat spinal cord. In order to investigate glycinergic mechanisms in spasticity, and other signs of the upper motor syndrome, we gave 4.5 and 6.0 g/day of L-threonine to 18 patients with familial spastic paraparesis (FSP) according to a double-blind, crossover protocol. The response to treatment at the end of each 2-week period was based upon three measures: the physician's global impressions; the patients' global impressions; and semiquantitative ratings of strength, muscle tone, DTRs, walking, hopping, and running. Blood and CSF were collected during each treatment period for amino acid analyses. Based upon the severity rating scales, there was a statistically significant (p less than 0.02) decrease in motor impairment and spasticity during L-threonine administration compared to placebo treatment; significant treatment effects were not found on the physician's and patients' global impressions. Plasma and CSF levels of threonine increased significantly during L-threonine treatment but glycine levels did not change. These data indicate that L-threonine significantly suppressed the signs of spasticity even though the benefits were not clinically valuable.
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PMID:L-threonine in the treatment of spasticity. 174 49

We conducted a double-blind, placebo-controlled, crossover study of oral L-threonine at 6 g/day in patients with spinal spasticity. Muscle tone from selected leg muscles, measured by the Ashworth Scale, was the principal measure of spasticity and was evaluated before and at the end of each treatment period. A 10% reduction in Ashworth score was regarded as a positive response to a treatment. The results were analyzed sequentially, patients being classified as threonine-responders, placebo-responders or non-responders (those who responded to both treatments by either less or greater than 10%) and a level of significance of p = 0.05 was chosen. The trial concluded in favour of L-threonine after 33 patients. Side-effects were minimal. L-threonine has a modest but definite antispastic effect, and its possible role in modifying spinal glycinergic transmission is discussed.
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PMID:A double-blind study of L-threonine in patients with spinal spasticity. 829 31

Hereditary spastic paraplegias (HSPs) are a large group of genetically-diverse neurologic disorders characterized clinically by a common feature of lower extremity spasticity and gait difficulties. Current therapies are predominantly symptomatic, and even then usually provide inadequate relief of symptoms. Going forward, HSP therapeutics development requires a systematic analysis of quantifiable measures and tools to assess treatment response. This review summarizes promising therapeutic targets, assessment measures, and previous clinical trials for the HSPs. Oxidative stress, signaling pathways, microtubule dynamics, and gene rescue/replacement have been proposed as potential treatment targets or modalities. Quantitative evaluation of pre-clinical rodent HSP models emphasize rotarod performance, foot base angle, grip strength, stride length, beam walking, critical speed, and body weight. Clinical measures of HSP in humans include 10-m gait velocity, the Spastic Paraplegia Rating Scale (SPRS), Ashworth Spasticity Scale, Fugl-Meyer Scale, timed up-and-go, and the Gillette Functional Assessment Questionnaire. We conducted a broad search for past clinical trials in HSPs and identified trials that investigated pharmacological agents including atorvastatin, gabapentin, L-threonine, botulinum toxin, dalfampridine, methylphenidate, and baclofen. We provide recommendations for future HSP treatment directions based on these prior research experiences as well as regulatory insight.
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PMID:Clinical Trial Designs and Measures in Hereditary Spastic Paraplegias. 3062 15