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  Cardiac arrhythmia treatment methodsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Whole Live Micro-organism, Cell, Or Virus Containing, Genetically Modified Micro-organism, Cell, Or Virus (e.g., Transformed, Fused, Hybrid, Etc.)The Patent Description & Claims data below is from USPTO Patent Application 20070048284. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATION [0001] The present application claims priority to U.S. Provisional Application No. 60/230,311, filed on Sep. 6, 2000, and U.S. Provisional Application No. 60/295,889, filed on Jun. 5, 2001, the disclosure of which are both incorporated herein by reference. FIELD OF THE INVENTION [0003] The invention generally features methods for the prevention or treatment of heart arrhythmia. Preferred methods generally involve administering at least one therapeutic polynucleotide to a mammal sufficient to modulate at least one electrical property of the heart. Modulation of the electrical property addresses the arrhythmia typically by encouraging normal heart electrical function. BACKGROUND [0004] The mammalian heart is understood to maintain an intrinsic rhythm by creating electric stimuli. Generally, the stimuli form a depolarization wave that propagates within specialized cardiac conducting tissue and the myocardium. The usually well-ordered wave movement facilitates coordinated contractions of the myocardium. These contractions are the engine that moves blood throughout the body. See generally The Heart and Cardiovascular System. Scientific Foundations. (1986) (Fozzard, H. A. et al. eds) Raven Press, NY. [0005] Under most circumstances, cardiac stimuli are controlled by recognized physiological mechanisms. However there has been long-standing recognition that abnormalities of excitable cardiac tissue can lead to abnormalities of the heart rhythm. These abnormalities are generally referred to as arrhythmias. Most arrhythmias are believed to stem from defects in cardiac impulse generation or propagation that can substantially compromise homeostasis, leading to substantial patient discomfort or even death. For example, cardiac arrhythmias that cause the heart to beat too slowly are known as bradycardia, or bradyarrhythmia. In contrast, arrhythmias that cause the heart to beat too fast are referred to as tachycardia, or tachyarrhythmia. See generally Cardiovascular Arrhythmias (1973) (Dreifus, L. S. and Likoff, W. eds) Grune & Stratton, NY. [0006] The significance of these and related heart disorders to public health cannot be exaggerated. Symptoms related to arrhythmias range from nuisance, extra heart beats, to life-threatening loss of consciousness. Complete circulatory collapse has also been reported. Morbidity and mortality from such problems continues to be substantial. In the United States alone for example, cardiac arrest accounts for 220,000 deaths per year. There is thought to be more than 10% of total American deaths. Atrial fibrillation, a specific form of cardiac arrhythmia, impacts more than 2 million people in the United States. Other arrhythmias account for thousands of emergency room visits and hospital admissions each year. See eg., Bosch, R. et al. (1999) in Cardiovas Res. 44: 121 and references cited therein. [0007] Cardiac electrophysiology has been the subject of intense interest. Generally, the cellular basis for all cardiac electrical activity is the action potential (AP). The AP is conventionally divided into five phases in which each phase is defined by the cellular membrane potential and the activity of potassium, chloride, and calcium ion channel proteins that affect that potential. Propagation of the AP throughout the heart is thought to involve gap junctions. See Tomaselli, G. and Marban, E. (1999) in Cardiovasc. Res. 42: 270 and references cited therein. [0008] There have been limited attempts to treat cardiac arrhythmias and related heart disorders. [0009] Specifically, many of the past attempts have been confined to pharmacotherapy, radiofrequency ablation, use of implantable devices, and related approaches. Unfortunately, this has limited options for successful patient management and rehabilitation. [0010] In particular, radiofrequency ablation has been reported to address a limited number of arrhythmias eg., atrioventricular (AV) node reentry tachycardia, accessory pathway-mediated tachycardia, and atrial flutter. However, more problematic arrhythmias such as atrial fibrillation and infarct-related ventricular tachycardia, are less amenable to this and related therapies. Device-based therapies (pacemakers and defibrillators, for instance) have been reported to be helpful for some patients with bradyarrhythmias and lifesaving for patients with tachyarrhythmias. However, such therapies does not always prevent tachyarrhythmias. Moreover, use of such implementations is most often associated with a prolonged commitment to repeated procedures, significant expense, and potentially catastrophic complications including infection, cardiac perforation, and lead failure. [0011] Drug therapy remains a popular route for reducing some arrhythmic events. However, there has been recognition that systemic effects are often poorly tolerated. Moreover, there is belief that proarrhythmic tendencies exhibited by many drugs may increase mortality in many situations. See generally Bigger, J. T and Hoffman, B. F. (1993) in The Pharmacological Basis of Therapeutics 8.sup.th Ed. (Gilman, A. G et al. eds) McGraw-Hill, NY and references cited therein. [0012] It would be desirable to have more effective methods for treating or preventing cardiac arrhythmias. It would be especially desirable to have gene therapy methods for treating or preventing such arrhythmias. SUMMARY OF THE INVENTION [0013] The present invention provides methods of preventing or treating cardiac arrhythmia in a mammal. In general, the methods involve administering to the mammal at least one polynucleotide that preferably modulates at least one electrical property of the heart. Use of the polynucleotides according to the invention modulates the heart electrical property, thereby preventing or treating the cardiac arrhythmia. [0014] There has been a long-felt need for more effective anti-arrhythmic therapies. The invention addresses this need by providing, for the first time, therapeutic methods for administering one or more therapeutic polynucleotides to the heart under conditions sufficient to modulate (increase or decrease) at least one heart electrical property. Preferred use of the invention modulates heart electrical conduction preferably reconfigures all or part of the cardiac action potential (AP). That use helps achieve a desired therapeutic outcome. Significant disruption of normal electrical function is usually reduced and often avoided by the present methods. Moreover, use of the invention is flexible and provides, also for the first time, important anti-arrhythmic strategies that can be tailored to the health requirements of one patient or several as needed. [0015] The invention provides other advantages that have been heretobefore difficult or impossible to achieve. For example, and unlike prior practice, the invention methods are genetically and spatially controllable ie., they provide for administration of at least one pre-defined polynucleotide to an identified heart tissue or focal area. Since there is recognition that many protein encoding polynucleotides can be expressed successfully in heart tissue, the invention is a generally applicable anti-arrhythmia therapy that can be employed to supply the heart with one or a combination of different therapeutic proteins encoded by the polynucleotides. Such proteins can be provided transiently or more long-term as needed to address a particular cardiac indication. [0016] The invention provides further benefits and advantages. For example, practice of prior anti-arrhythmic approaches involving pharmacotherapy, radiofrequency ablation, and implantable device approaches is reduced and oftentimes eliminated by the invention. Moreover, the invention provides, highly localized gene delivery. Importantly, treated cells and tissue usually remain responsive to endogenous nerves and hormones in most cases. In particular invention methods discussed below, localized coronary circulation provides targeted delivery to isolated regions of the heart. In some embodiments, proximity to endocardium allows access by intracardiac injection. Therapeutic effects are often readily detected eg., by use of standard electrophysiological assays as provided herein. Also importantly, many gene transfer-induced changes in accord with the present invention can be rescued, if needed, by conventional electrophysiological methods. [0017] Accordingly, and in one aspect, the invention provides methods for preventing or treating cardiac arrhythmia. More specific methods include administering to a mammal a therapeutically effective amount of at least one polynucleotide that can increase or decrease at least one electrical property as determined by one or more standard electrophysiological assays. Examples of preferred administration routes, polynucleotides, and assays are provided in the discussion that follows. Preferably, the invention further includes expressing the polynucleotide in the mammal sufficient to prevent or treat the cardiac arrhythmia. In general, polynucleotide expression conducive to using the invention is apparent as a shift in a recording (relative to baseline) obtained from at least one of the standard electrophysiological assays. [0018] In additionally preferred invention methods, the electrical property is increased or decreased by at least about 10% relative to a baseline function. More preferably, the increase or decrease is at least about 20%, more preferably at least about 30% to about 50% or more. That baseline function can be readily ascertained eg., by performing the electrophysiological assay on a particular mammal prior to conducting the invention methods. Alternatively, related baseline function can be determined by performing a parallel experiment in which a control polynucleotide is administered instead of the polynucleotide of interest. It will be apparent that once a reliable baseline function has been established (or is available from public sources) determination of the baseline function by the practitioner may not always be necessary. Examples of relevant electrical properties are known and include, but are not limited to, at least one of refractoriness, speed of conduction, focal automaticity, and spatial excitation pattern. [0019] The invention is widely applicable to the prevent and treatment of a wide range of ventricular or atrial arrhythmias including atrial fibrillation. Accordingly, the invention provides, in one embodiment, methods for treating atrial fibrillation that include administering to a mammal a therapeutically effective amount of at least one polynucleotide encoding an inhibitory G protein subunit, preferably G.alpha..sub.i2 subunit; or a functional fragment thereof. Preferred method practice involves expressing the polynucleotide in the mammal to treat the atrial fibrillation, particularly by controlling heart rate. Additional prevention and treatment methods are provided below. [0020] In another aspect, the invention provides a kit for performing one or a combination of the invention methods disclosed herein. Preferably, the kit includes at least one suitable myocardium nucleic acid delivery system and preferably at least one desired polynucleotide. Preferably, that polynucleotide is operably linked to the system i.e., it is in functional and/or physical association therewith sufficient to provide for good administration of the polynucleotide into the heart. Additionally preferred kits include means for administering the polynucleotide to the mammal such as a syringe, catheter and the like. [0021] The invention also includes a device useful for the therapeutic methods disclosed herein. Preferred devices include those unitary, integral devices elate position of the device within a subject, particularly proximate to a patient's heart, as well as deliver a therapeutic agent to a patient, particularly a nucleic acid therapeutic to a mammalian heart. Specifically preferred devices comprise an elongate member, particularly a flexible catheter member that can be advanced to a patient's heart. The catheter unit suitably comprises a administration member, e.g. a needle member, for delivering a therapeutic agent especially a polynucleotide to cardiac tissue of the patient. The catheter unit also includes positioning detection apparatus such as detectable electrodes at the catheter's distal end. Continue reading... Full patent description for Cardiac arrhythmia treatment methods Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Cardiac arrhythmia treatment methods patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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