Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Botulinum neurotoxin serotype A (BoNT/A) has revolutionised the treatment of a variety of autonomic hypersecretory disorders. Several open and controlled studies indicate that BoNT/A is a safe and effective treatment for focal hyperhidrosis of the axillae and palms, for gustatory sweating, and for some other rare conditions associated with focal hyperhidrosis. There is class I evidence for the efficacy of botulinum toxin in axillary hyperhidrosis and class II evidence for palmar hyperhidrosis and gustatory sweating. BoNT/A has the potential to replace current invasive and surgical techniques and should at least be considered as a viable alternative. The results of pilot studies to treat sialorrhea are encouraging. However, the optimal dose, best mode of application, side effects, and duration of BoNT/A action in this condition remain uncertain. We need further formal clinical trials to evaluate risks and benefits of BoNT/A for palliative treatment in of sialorrhea in Parkinson's disease and in bulbar amyotrophic lateral sclerosis. Based on the few reports published, BoNT/A injections into the lacrimal gland for hyperlacrimation may be an elegant method to treat this sometimes disabling condition. Again, larger studies are needed to evaluate the risks and long-term benefits of this treatment option.
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PMID:Botulinum toxin treatment of secretory disorders. 1502 66

Seven children between 2 and 15 years of age with cerebral palsy and upper extremity dystonia were enrolled in an open-label, dose-escalation pilot clinical trial of botulinum toxin type B (Myobloc), injected into the biceps and brachioradialis muscles of I or both arms. The primary outcome measure was the change in maximum speed of hand movement during attempted forward reaching. Escalating doses of 12.5, 25, and 50 U/kg per muscle were injected at each of 3 visits. Reaching speed improved in response to injection, and dystonia scores on the Burke-Fahn-Marsden dystonia scale, the Unified Dystonia Rating Scale, and the Unified Parkinson's Disease Rating Scale improved. There was not a dose-related effect on efficacy. There were no serious adverse events. Two children reported transient weakness. These results support the use of botulinum toxin type B as a safe and effective treatment for upper extremity dystonia in children with cerebral palsy. Larger controlled trials are needed to confirm these results.
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PMID:Botulinum toxin type B improves the speed of reaching in children with cerebral palsy and arm dystonia: an open-label, dose-escalation pilot study. 1760 20

The protein botulinum neurotoxin A (BoNT/A) is one of seven distinct neurotoxins produced by Clostridium botulinum. BoNT/A blocks cholinergic synapses with an extremely high specificity and potency. Appropriately purified and diluted, BoNT/A serves as a reliable and well tolerated drug that is applied by local injection.The efficacy of BoNT/A is evident in the symptomatic therapy of disorders in which muscular hyperactivity plays a prominent role, such as focal dystonias and hemifacial spasm; in these disorders, BoNT/A is considered first-line therapy. BoNT/A is also beneficial in the treatment of both adults and children with spasticity of various causes. The pain that frequently accompanies these conditions is effectively reduced by BoNT/A. A genuine analgesic effect for BoNT/A unrelated to skeletal muscle spasmolysis has been suggested on the basis of in vitro and in vivo (animal) data. However, studies in humans designed to detect such an effect were negative, as were controlled studies of BoNT/A in patients with primary headache disorders.BoNT/A also acts on cholinergic synapses of the autonomic nervous system, and injection of BoNT/A into salivary glands significantly decreases the production of saliva. This may be beneficial for patients with Parkinson's disease, in whom the excessive production of saliva may be problematic.Overall, BoNT/A has been confirmed as an efficacious, predictable and well tolerated drug in an ever-increasing number of neurological disorders.
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PMID:Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety. 1869 73

Recent reports indicate that interruption of acetylcholine release by intrastriatal injection of botulinum neurotoxin type A (BoNT/A) in a rat Parkinson's disease model reduces pathogenic behavior without adverse side effects such as memory dysfunction. Current knowledge suggests that BoNT/A subtype 1 (BoNT/A1) and BoNT/A subtype 2 (BoNT/A2) exert different effects. In the present study, we compared the effects of BoNT/A1 and BoNT/A2 on rotation behavior and in vivo cleavage of presynaptic protein SNAP-25 in a rat unilateral 6-hydroxydopamine-induced Parkinson's disease model. BoNT/A2 more effectively reduced pathogenic behavior by efficiently cleaving SNAP-25 in the striatum compared with that of BoNT/A1. Our results suggest that BoNT/A2 has greater clinical therapeutic value for treating subjects with Parkinson's disease compared to that of BoNT/A1.
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PMID:Botulinum neurotoxin A subtype 2 reduces pathological behaviors more effectively than subtype 1 in a rat Parkinson's disease model. 2471 2

Botulinum neurotoxin type A (BoNT/A) cleaves SNAP-25 and interrupts the release of acetylcholine. We previously reported that BoNT/A subtype 2 (BoNT/A2) ameliorates pathologic behavior more effectively than subtype 1 (BoNT/A1) in a rat Parkinson's disease model. Here, we further show BoNT/A2 has fewer adverse effects than BoNT/A1. We first confirmed that intrastriatal treatments of both BoNT/As had no-effect on dopaminergic terminals in the striatum. SNAP-25 cleaved by BoNT/A2 was strictly localized to the striatum on the injected side; however, SNAP-25 cleaved by BoNT/A1 diffused contralaterally. Furthermore, treatment with BoNT/A1 caused a significant reduction in body weight, while BoNT/A2 treatment did not. These results suggest that BoNT/A2 is more beneficial for clinical application against Parkinson's disease than BoNT/A1.
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PMID:Botulinum neurotoxin type A subtype 2 confers greater safety than subtype 1 in a rat Parkinson's disease model. 2484 52

Neurodegenerative disorders have been and remain persistent sources of enormous suffering throughout human history. The tragedy of their impact on human relationships, physical vitality, and fundamental dignity cannot be understated. Parkinson's disease (PD), one of the most common of these terrible illnesses, has a global incidence of approximately two-to-four percent of the human population, along with devastating social and economic impact. The present review analyzes aspects of PD pathophysiology that offer particularly attractive strategies for the development of improved prevention and therapy. The occurrence, symptoms, pathogenesis, and etiology of PD are considered, with focus on how the Alpha synuclein protein, which normally regulates neurotransmitter release, is aggregated by oxidative stressors into toxic inclusions, prominently including Lewy bodies and insoluble fibrils that disrupt the organization of brain areas responsible for motor control. The contribution to a progressively prooxidant tissue environment resulting from interaction between advanced glycation end products (AGEs) and their cognate receptors (RAGEs) is examined here as a significant driver of PD. This review also explores strategies currently being developed by a U.S.-Russian team that may reduce the risk and severity of PD by use of recombinant atoxic derivatives (ad) of botulinum neurotoxins (BoNT/A ad), that traffic inducers of the cytoprotective enzyme heme oxygenase to selected midbrain neurons, at which Alpha synuclein aggregation occurs. Considered together, the topic material presented here provides both researchers and clinicians with a short but concise overview of the current understanding of PD pathology and approaches to biotherapeutic (precision) countermeasures to its onset and progression.
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PMID:Parkinson's Disease: Alpha Synuclein, Heme Oxygenase and Biotherapeutic Countermeasures. 3001 39