Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retrograde axonal transport of recombinant adenoviral vectors has been used successfully to deliver genes to motoneurons in rodents after injection of the vectors into muscles. However, only a small proportion of motoneurons take up and retrogradely transport adenoviral particles, limiting the value of this gene delivery method for the treatment of motor neuron diseases (MNDs). Here we validate a new pharmacological approach for enhancing motoneuronal gene transfer after intramuscular injection of recombinant adenoviruses. We injected botulinum neurotoxin A (BoNT) into muscles of normal C57BL/6 mice and transgenic mice expressing the G93A mutation in the superoxide dismutase 1 gene (SOD1-G93A mutation, a model of amyotrophic lateral sclerosis) several days before inoculation with adenoviruses. Treatment with BoNT significantly enhanced gene transfer to motoneurons innervating the injected muscles. Modifications in motoneuron transduction appear to be a consequence of toxin-induced nerve sprouting at the end plates. These findings have major implications for devising protocols for preclinical and clinical studies using intramuscular injection of retrogradely transported gene vectors.
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PMID:Adenoviral retrograde gene transfer in motoneurons is greatly enhanced by prior intramuscular inoculation with botulinum toxin. 1181 79

Primary focal hyperhidrosis is a common autonomic disorder that significantly impacts quality of life. It is characterized by excessive sweating confined to circumscribed areas, such as the axillae, palms, soles, and face. Less frequent types of focal hyperhidrosis secondary to underlying causes include gustatory sweating in Frey's syndrome and compensatory sweating in Ross' syndrome and after sympathectomy. Approval of onabotulinumtoxinA for severe primary axillary hyperhidrosis in 2004 has revolutionized the treatment of this indication. Meanwhile further type A botulinum neurotoxins like abobotulinumtoxinA and incobotulinumtoxinA, as well as the type B botulinum neurotoxin rimabotulinumtoxinB are successfully used off-label for axillary and various other types of focal hyperhidrosis. For unexplained reasons, the duration of effect differs considerably at different sites. Beside hyperhidrosis, botulinum neurotoxin is also highly valued for the treatment of sialorrhea affecting patients with Parkinson's disease, cerebral palsy, amyotrophic lateral sclerosis, motor neuron disease, and other neurologic conditions. With correct dosing and application, side effects are manageable and transient.
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PMID:Botulinum Toxin Treatment of Autonomic Disorders: Focal Hyperhidrosis and Sialorrhea. 2686 92

Pain is an important non-motor symptom in several neurological diseases, such as Parkinson's disease, cervical dystonia, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness and dementia, as well as in oncology and neuroinfectivology. To overcome the lack of evidence-based data on pain management in these diseases, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) has defined criteria for good clinical practice among Italian neurorehabilitation professionals. Here a review of the literature (PubMed, EMBASE and gray literature) on pain characteristics, treatment and impact of pain in a neurorehabilitation setting is provided. Despite the heterogeneity of data, a consensus was reached on pain management for patients with these diseases: it is an approach originating from an analysis of the available data on pain characteristics in each disease, the evolution of pain in relation to the natural course of the disease and the impact of pain on the overall process of rehabilitation. There was unanimous consensus regarding the utility of a multidisciplinary approach to pain therapy, combining the benefits of pharmacological therapy with the techniques of physiotherapy and neurorehabilitation for all the conditions considered. While some treatments could be different depending on pathology, a progressive approach to the pharmacological treatment of pain is advisable, starting with non-opioid analgesics (paracetamol) and nonsteroidal anti-inflammatory drugs as a first-line treatment, and opioid analgesics as a second-line treatment. In cases of pain secondary to spasticity, botulinum neurotoxin, and, in some cases, intrathecal baclofen infusion should be considered. Randomized controlled trials and prospective multicenter studies aimed at documenting the efficacy of pain treatment and their risk-benefit profile are recommended for these conditions.
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PMID:Assessing and treating pain in movement disorders, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness, dementia, oncology and neuroinfectivology. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation. 2757 82

Fifteen ALS patients, with troublesome symptoms linked to masseter spasticity, benefited from BoNT-A injections in each masseter. Based on the medical records of patients, the effect of the first injection was assessed one month later. We retrospectively collected information for 12 patients. Eight of them reported a beneficial effect after the injection for the following symptoms: trismus, tongue, lip and cheek biting, and jaw clonus. Five patients indicated that dental care was easier after injection. Our study showed that injections of BoNT-A unequivocally reduced masseter spasticity in ALS patients who subsequently enjoyed greater comfort in their daily living.
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PMID:Botulinum toxin therapy improves masseter spasticity in Amyotrophic Lateral Sclerosis. 3265 15