Muscular dystrophy

Description:

Muscular dystrophy represents group of chronic hereditary diseases of the skeletal muscles of the person which are shown weakness and a degeneration of muscles. There are nine various forms of muscular dystrophy. They differ according to such characteristics as age at which the disease, localization of the affected muscles, expressiveness of muscular weakness, speed of progressing of dystrophy and type of its inheritance begins. Most often two forms meet: muscular dystrophy of Dyushenn and miotonichesky muscular dystrophy.

Symptoms of Muscular dystrophy:

Dyushenna dystrophy. H-chromosomal recessive mutation of a distrofin-gene. Clinical signs: the beginning aged up to 5 years; the progressing weakness of muscles of a pelvic and shoulder girdle; inability to go after 12 years; kyphoscoliosis; respiratory insufficiency at the age of 20-30 years. Involvement of other systems of bodies: cardiomyopathy; decrease in intelligence.

Becker dystrophy. H-chromosomal recessive mutation of a distrofin-gene. Clinical signs: the beginning at early or late age; slowly progressing weakness of muscles of a pelvic and shoulder girdle; preservation of ability to go after 15 years; respiratory insufficiency after 40 years. Involvement of other systems of bodies: cardiomyopathy.

Miotonichesky dystrophy. Autosomal dominant; expansion of the unstable site of DNA of a chromosome 19ql3,3. Clinical signs: the beginning at any age; slowly progressing weakness of muscles a century, persons, necks, distal muscles of extremities; myatonia. Involvement of other systems of bodies: disturbance of cordial conductivity; mental disturbances; cataracts, frontal alopecia; atrophy of gonads.

Shoulder - scapular and front dystrophy.

Autosomal and dominant; often chromosome mutations 4q35. Clinical signs: the beginning aged up to 20 years; slowly progressing muscular weakness of front area, a shoulder girdle, foot dorsiflexion. Involvement of other systems of bodies: hypertensia; deafness.

Shoulder and pelvic girdle (several diseases are possible). Autosomal and recessive or dominant. Clinical signs: began with the early childhood to middle age; slowly progressing weakness of muscles of a shoulder and pelvic girdle. Involvement of other systems of bodies: cardiomyopathy.
Glazo-glotochnaya dystrophy. Autosomal and dominant (French Canada or Spain). Clinical signs: the beginning in 50-60 years; slowly progressing weakness of muscles: outside eye, century, persons and drinks; cricopharingeal achalasia. Involvement of other systems of bodies: cerebral, eye.
Inborn dystrophy. Includes several diseases, including types Fukuyama and a tserebro-ocular dysplasia). Autosomal and recessive. Clinical signs: the beginning at the birth; hypotonia, contractures, arrest of development; in one cases — early respiratory insufficiency, in others — more favorable disease.

Reasons of Muscular dystrophy:

The disease is caused by an autosomal and dominant gene with sharply varying expressivity (the possibility of risk of transfer on relatives of the 1st degree makes 50%). The disease is caused by amplification, i.e. increase in number of CTG - triplets in a certain locus of the 19th chromosome (type 1 of miotonichesky dystrophy) or CCTG in the 3rd chromosome (tip2 miotonichesky dystrophy). Type 2 of miotonichesky dystrophy is studied poorly. It is considered that it meets only in 2% of cases (but maybe is much more often); it is not interconnected with type 1; most likely is not the reason of inborn forms of dystrophy when the carrier is mother. For 1 type it is proved that the number of repetitions of nucleotides increases by transfer of a mutation from generation to generation. Disease severity accurately correlates with a number of these repetitions. Their greatest number is defined at an inborn severe form of a disease [Brook J. D. et al., 1992]. The revealed mechanism explains an antitsipation phenomenon — weighting and more and more early onset of the illness in the descending generations. For example, if the genetic analysis showed that the parent has a certain number of repetitions of CTG, then a bigger number of repetitions of this triplet will be found in his child.

Treatment of Muscular dystrophy:

Today there are no ways to prevent or slow down progressing of this disease. Therapy is directed mainly to fight against complications, such as the deformation of a backbone developing owing to weakness of muscles of a back or the predisposition to pneumonia caused by weakness of respiratory muscles. Phenytoinum, procaineamide, quinine are applied in treatment of a myatonia, but care is required from patients with heart diseases (danger of deterioration in cordial conductivity). Implantation of the driver of a cordial rhythm is necessary for patients with a syncope or cordial blockade. At treatment of cordial disturbances drug Phenihydinum is recommended. Use of orthoses can strengthen "trailing" feet, stabilize ankle joints, reduce the frequency of falling. Well picked up training can also exert positive impact on the course of this disease. In the presence of an atrophy apply anabolic steroids (retabolil, Nerobolum), fortifying therapy. When there is much an expressed miotonichesky symptomatology, appoint dipheninum courses on 0,03 — 0,05 g 3 times a day, lasting 2 — 3 weeks. Assume that dipheninum has the oppressing effect on synaptic conduction and reduces post-tetanic activity in muscles. At the increased drowsiness which is quite often accompanying miotonichesky dystrophy, the positive effect is observed at reception of a selegilin. Also reception of some dietary supplements is recommended: Q10 coenzyme (100 mg/day), vitamin E (200 ME/day) and selenium (200 mkg/day), lecithin (20 g/day).

Effective treatment from this disease is possible only by means of gene therapy which now intensively develops. Numerous experiments show improvement of a condition of muscle fibers at treatment of some forms of muscular dystrophy. At Dyushen and Becker's dystrophies insufficient production of muscle protein of a distrofin is observed. The gene responsible for production of this protein is the biggest of all known genes therefore for performing gene therapy scientists created the tiny version of this gene. The best conductors of a gene to muscles scientists recognized adenoviruses. Therefore in adenovirus they placed the necessary gene and entered it to the mice suffering from a lack of a distrofin. Results of experience were encouraging. In other similar works as carriers of this gene liposomes, microspheres, lactoferrin are. Original approach to genoterapevtichesky treatment of MDD is developed at the Oxford university by group under the direction of Kay Davies. The essence of a method consists in attempt of derepression of an autosomal homolog of a distrofin – a gene of an utrofin which product of an expression could be capable to compensate a lack of a distrofin of all groups of muscles. In an embryogenesis of the person approximately up to seven weeks of development дистрофин does not express and its function in muscles is performed by protein утрофин. In an interval between the seventh and 19 weeks of development both proteins express and after the 19th week there is substitution of a muscular utrofin on дистрофин. After the 19th week of embryonic development утрофин it is found only in the field of neuromuscular contacts. Protein утрофин, having autosomal localization strikingly reminds дистрофин the N-and S - the trailer domains playing a crucial role as a distrofin. Results of experiments indicate a basic possibility of correction of defects in the muscle fibers deprived of a distrofin by means of an utrofin Is established that two drugs (L-arginine and heregulin) increase production of protein атрофин in muscle cells of mice. The increased quantity of an atrofin probably partially will compensate absence or a lack of protein дистрофин which is observed at different types of muscular dystrophy. Before these drugs will be used in treatment of people, scientists still should investigate their safety and efficiency. In a human body there is a protein Myostatinum (myostatin) which limits muscle growth. Researchers noted improvement of a condition of muscles of the mice sick with muscular dystrophy of Dyushen, after blocking of this protein. The biotechnological company works on creation of drug which will be able to block Myostatinum at mice, and plans further tests which would allow to use this technology at treatment of different types of muscular dystrophy at people.