Heart related complications in muscular dystrophies are serious concern. The cardiomyopathy and cardiac arrhythmias are caused by defects in cardiomyocyte and cardiac conduction system function. Unlike the skeletal muscle degenerative process, for which treatment options are currently limited, therapy is available for the cardiovascular complications. New therapies for muscle degeneration are moving into clinical trials and are expected to also improve the cardiac function, longevity and wellbeing of muscular dystrophy patients.
The muscular dystrophies are muscle destroying disorders. There are at least 21 different monogenic causes of muscular dystrophy, and cardiovascular complications are commonly associated with some subtypes.[1] Currently there is no established cure but data available to support various anti-oxidants and ayurvedic herbs such as Curcuma longa and Terminalia arjuna, based approaches to management of cardio myopathy. Cardiomyopathy in the muscular dystrophies can develop to heart failure.
There are several subtypes of muscular dystrophies, which are categorized based on genetics and molecular pathogenesis:-
(1) The Dystrophin Glycoprotein Complex: Being important for membrane stability, it plays a particularly important part in the muscular dystrophies, because mutations in the genes that encode its constituent proteins result in a distinct group of progressive degenerative muscle disorders. [2,3] Mutations in the genes encoding dystrophin or the SARCOGLYCAN proteins cause myofibers and cardio myocytes to be abnormally susceptible to contraction-induced damage.[4—6] The loss of the dystrophin protein, as occurs in most forms of Duchenne muscular dystrophy, is associated with destabilization of all the dystrophin-associated proteins, including the sarcoglycans. [7] Membrane instability in cardiomyocyte and skeletal myofibers is associated with leakage of muscle-specific enzymes into the serum. Creatine kinase levels are substantially raised in these patients, and both the MM and MB isoforms are detected. Elevation of the MB isoform often indicates cardiomyocyte degeneration.
(2) Telethonin, Titin and Myotilin: Mutations in these genes lead to rare forms of muscular dystrophy.[9—13] Telethonin is thought to be important for passive stretch in cardiomyocytes.
(3) Nuclear Membrane Proteins: The LMNA gene encodes the inner nuclear membrane proteins lamin A & C. They regulate a number of nuclear processes, including DNA replication, transcription, chromatin attachments and nuclear transport.[14]
(4) Additional Membrane-Associated Proteins: Dysferlin is a transmembrane protein that binds phospholipids in a calcium dependent manner and is highly expressed in skeletal and cardiac muscle.[15—18] Mutations in DYSF result in abnormal muscle membrane repair.
New experimental therapies for muscular dystrophies are now emerging. Gene replacement therapy, Ayurvedic Rasayana based therapies are also being explored for the regeneration of muscles. The cardiac problems associated with some forms of muscular dystrophy sometimes need treatment. Terminalia Arjuna has remarkable cardio protective, heart muscle strengthening properties. Current scientific research has proved that plant contains specific medically active constituents namely triterpine glycosides like arjunetosides I, II, III, IV, arjunine and arjunetein, phytosterols, rich in minerals like calcium, magnesium, zinc and copper. Regular use of Arjuna improves pumping activity of heart, improves cardiac muscle strength, decrease in LDL cholesterol levels. It has been reported to possess protective cardiovascular and hypolipidemic properties.[19-20] Finally, growth-factor-based gene therapy is emerging as a successful approach for stimulating muscle growth.
Cardiac arrhythmias can be life threatening, and muscular dystrophy patients should be monitored closely for signs and symptoms of cardiac arrhythmia events. As with all cardiomyopathy patients, treatment aimed at arrhythmia prevention should be sought. And from this point of view, ayurvedic therapies and remedies are good options. Mamsagmi Rasayana is a promising molecule being scientifically verified. Get more assess at http://www.ayush-samiti.in
References:
1. Laval SH and Bushby KM (2004) Limb-girdle muscular dystrophies?from genetics to molecular pathology. Neuropathol Appl Neurobiol 30: 91-105
2. Lapidos KA et al. (2004) The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma. Circ Res 94: 1023-1031
3. Blake DJ and Martin-Rendon E (2002) Intermediate filaments and the function of the dystrophin-protein complex. Trends Cardiovasc Med 12: 224-228
4. Petrof BJ et al. (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci U S A 90: 3710-3714
5. Danialou G et al. (2001) Dystrophin-deficient cardiomyocytes are abnormally vulnerable to mechanical stress-induced contractile failure and injury. Faseb J 15: 1655-1657
6. Dellorusso C et al. (2001) Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury. J Muscle Res Cell Motil 22: 467-475
7. Matsuda R et al. (1995) Visualization of dystrophic muscle fibers in mdx mouse by vital staining with Evans blue: evidence of apoptosis in dystrophin-deficient muscle. J Biochem (Tokyo) 118: 959-964
8. McLaurin MD et al. (1997) Cardiac troponin I, cardiac troponin T, and creatine kinase MB in dialysis patients without ischemic heart disease: evidence of cardiac troponin T expression in skeletal muscle. Clin Chem 43: 976-982
9. Moreira ES et al. (2000) Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 24: 163-166
10. Hauser MA et al. (2000) Myotilin is mutated in limb girdle muscular dystrophy 1A.
Hum Mol Genet 9: 2141-2147
11. Hackman P et al. (2002) Tibial muscular dystrophy is a titinopathy caused by mutations in TTN,
the gene encoding the giant skeletal-muscle protein titin. Am J Hum Genet 71: 492-500
12. Knoll R et al. (2002) The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 111: 943-955
13. Omens JH et al. (2002) Muscle LIM protein deficiency leads to alterations in passive ventricular mechanics. Am J Physiol Heart Circ Physiol 282: H680-H687
14. Ostlund C and Worman HJ (2003) Nuclear envelope proteins and neuromuscular diseases. Muscle Nerve 27: 393-406
15. Bashir R et al. (1998) A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet 20: 37-42
16. Anderson LV et al. (1999) Dysferlin is a plasma membrane protein and is expressed early in human development. Hum Mol Genet 8: 855-861
17. Davis DB et al. (2002) Calcium-sensitive phospholipid binding properties of normal and mutant ferlin C2 domains. J Biol Chem 277: 22883-22888
18. Liu J et al. (1998) Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet 20: 31-36
19. Alpana Rama, P. Lauria, R Gupta, et al (1997): Hypocholesterolaemic effects of Terminalia Arjuna, Journal of Ethno pharmacology, Vol 55:3, 1997, Pages 165-169
20. Jain Mukesh D (2003): Ayurvedic Management of Duchenne Muscular dystrophy: A research report: Light on Ayurveda, Journal of Health, winter issue 2, Mashpee (USA)
Article Source: http://www.articlesbase.com
About the Author
The Ayush Muscular Dystrophy Society has been active in the field of authentic Ayurvedic supportive treatment and rehabilitation since 1995. A number of families of afflicted children are registered with AMD society, which is involved in helping families with information about all aspects of NMD including Ayurvedic and other complementary medical support, physiotherapy, diet, monitoring the breathing, and updates about what is new in the form treatments that may be in the pipeline.
