High frequency application of botulinum toxin therapy

Abstract

The present invention relates to methods for treating diseases and disorders by administering a composition containing the neurotoxic component of a Clostridium botulinum toxin complex, wherein the composition may be devoid of any other protein of the Clostridium botulinum toxin complex and wherein the composition is administered at short intervals and/or in high doses.

1 . A method of treating a disease or condition caused by or associated with hyperactive cholinergic innervation of muscles in a patient, the method comprising administering a composition comprising a therapeutically effective amount of a neurotoxic component of a  Clostridium botulinum  toxin complex, the composition being devoid of any other protein component of the  Clostridium botulinum  toxin complex, to remove partially or completely the treated disease or condition symptoms, wherein
 (a) the patient is a human,   (b) the composition is locally administered by injection of a non-lethal dose to a muscle exhibiting hyperactive cholinergic innervation, and   (c) the composition is administered at an interval that provides a stable quality of life for the patient, the interval comprising a first treatment and a second treatment, wherein the second treatment is carried out at a point in time when the efficacy of the first treatment begins to decline.   
     
     
         2 . The method of  claim 1 , wherein the second treatment is performed in order to improve the treatment effect of the first treatment. 
     
     
         3 . The method of  claim 1 , wherein the patient is a human, who has been treated with a  Clostridium botulinum  toxin but who complains about a decrease of the treatment effect and who requires an additional treatment within 3 months of a previous treatment. 
     
     
         4 . The method of  claim 1 , wherein the disease or condition is or involves dystonia of a muscle. 
     
     
         5 . The method of  claim 4 , wherein the dystonia
 (a) is selected from the group consisting of cranial dystonia, blepharospasm, oromandibular dystonia of the jaw opening type, oromandibular dystonia of the jaw dosing type, bruxism, Meige syndrome, lingual dystonia, apraxia of the eyelid opening, cervical dystonia, antecollis, retrocollis, laterocollis, torticollis, pharyngeal dystonia, laryngeal dystonia, spasmodic dysphonia of the adductor type, spasmodic dysphonia of the abductor type, spasmodic dyspnea, limb dystonia, arm dystonia, task specific dystonia, writer's cramp, musician's cramp, golfer's cramp, leg dystonia involving thigh adduction, thigh abduction, knee flexion, knee extension, ankle flexion, ankle extension, equinovarus deformity, foot dystonia involving striatal toe, toe flexion, toe extension, axial dystonia, Pisa syndrome, belly dancer dystonia, segmental dystonia, hemidystonia, generalized dystonia, dystonia in Lubag, dystonia in corticobasal degeneration, tardive dystonia, dystonia in spinocerebellar ataxia, dystonia in Parkinson's disease, dystonia in Huntington's disease, dystonia in Hallervorden Spatz disease, dopa-induced dyskinesia, dopa-induced dystonia, tardive dyskinesia, tardive dystonia, paroxysmal dyskinesia, paroxysmal dystonia, paroxysmal kinesiogenic dyskinesia, paroxysmal non-kinesiogenic dyskinesia, and paroxysmal action-induced dyskinesia; or   (b) involves a clinical pattern selected from the group consisting of torticollis, laterocollis, retrocollis, anterocollis, flexed elbow, pronated forearm, flexed wrist, thumb-in-palm and clenched fist.   
     
     
         6 . The method of  claim 4 , wherein the muscle is selected from the group consisting of ipsilateral splenius, contralateral sternocdeidomastoid, ipsilateral stemocleidomastoid, splenius capitis, scalene complex, levator scapulae, postvertebralis, ipsilateral trapezius, levator scapulae, bilateral splenius capitis, upper trapezius, deep postvertebralis, bilateral stemocleidomastoid, scalene complex, submental complex, brachioradialis, biceps  brachialis , pronator quadratus pronator  teres , flexor carpi radialis, flexor carpi ulnaris, flexor pollicis longus, adductor pollicis, flexor pollicis  brevis , flexor pollicis  opponens , flexor digitorum superficialis, and flexor digitorum  profundus.    
     
     
         7 . The method of  claim 1 , wherein the disease or condition is or involves spasticity of a muscle. 
     
     
         8 . The method of  claim 7 , wherein the spasticity is or is associated with a spastic condition in encephalitis and myelitis relating to autoimmune processes, multiple sclerosis, transverse myelitis, Devic syndrome, viral infections, bacterial infections, parasitic infections, fungal infections, hereditary spastic paraparesis, postapoplectic syndrome resulting from hemispheric infarction, postapoplectic syndrome resulting from brainstem infarction, postapoplectic syndrome resulting from myelon infarction, a central nervous system trauma involving a hemispheric lesion, a central nervous system trauma involving a brainstem lesion, a central nervous system trauma involving a myelon lesion, a central nervous system hemorrhage, an intracerebral hemorrhage, a subarachnoidal hemorrhage, a subdural hemorrhage or an intraspinal hemorrhage, a neoplasia, a hemispheric tumor, a brainstem tumor, a myelon tumor, post-stroke spasticity, or spasticity caused by cerebral palsy. 
     
     
         9 . The method of  claim 7 , wherein the muscle is a smooth or striated muscle. 
     
     
         10 . The method of  claim 1 , wherein the neurotoxic component is selected from the group consisting of type A, B, C, D, E, F, G or a mixture thereof. 
     
     
         11 . A method of treating a disease or condition caused by or associated with hyperactive cholinergic innervation of muscles in a patient, the method comprising administering a composition comprising a therapeutically effective amount of a neurotoxic component of a  Clostridium botulinum  toxin complex, to remove partially or completely the treated disease or condition symptoms, wherein
 (a) the patient is a human,   (b) the composition is locally administered by injection of a non-lethal dose to a muscle exhibiting hyperactive cholinergic innervation, and   (c) the composition is administered at an interval that provides a stable quality of life for the patient, the interval comprising a first treatment and a second treatment, wherein the second treatment is carried out at a point in time when the efficacy of the first treatment begins to decline.