Stem Cell Therapy in DMD

Stem Cell Therapy in DMD

Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder. It occurs due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein in the muscles that causes degeneration of skeletal and cardiac muscles. Genetic analysis of DMD patients show deletions/duplications in the exons of dystrophin gene. It is done by MLPA technique. Since dystrophin is a bigger gene the testing using NGS technique is preferred. Presently there is no definitive cure available so DMD is termed as one of incurable diseases but there are several options by which the progression of disease can be slowed. Currently only approved treatment for this disease is the use of steroids which help in slowing down the disease progression but other options like STEM CELL THERAPY by use of placenta or umbilical cord derived mesenchymal stem cells or use of autologous mono nuclear cell transplant, have proven their safety and efficacy. This type of stem cell therapy in DMD is the most upcoming treatment, because of high degree of safety and easy availability of treatment.

In the last few years, an increasing number of strategies have been developed as a possible therapeutic approach to restore dystrophin production and to preserve muscle mass. Exon skipping drugs like exondys 51 or eteplirsen is effective only in the cases where deletion of exon 51 is found in dystrophin gene. Currently stem cell therapy is effective in only 10 to 15 percent of DMD cases and is prohibitively expensive.
One more treatment option for nonsense mutation in dystrophin gene is translarna or ataluren, which works on stop codon read through technique. Currently it is under clinical trial only.

Gene Therapy
Recently clinical trial using micro dystrophin gene has also being carried out at some of the centres in USA, its early phase results are encouraging.
Role of Stem Cell Therapy in DMD
Use of placenta or umbilical cord derived Stem Cell Therapy in DMD is safe and effective Use of Autologous bone marrow derived stem cells is effective but of limited use Allogenic cord derived mesenchymal stem cells are nonreactive and easily available so can be received from any donor.
Stem cells not only decrease the swelling of muscles but also perform some amount of regeneration so effective for a longer period. Stem cells can be used repeatedly depending upon the condition of patient.
It has no side effects like high blood sugar or weight gain or moon facies, which we get with long term use of steroids Stem cells should be used with the aim of improving quality of life and longevity Stem cell therapy is not curative but adjuvant or supportive therapy.

Role of stem cells therapy in DMD with cardio respiratory insufficiency Allogenic MSCs have shown very good improvement in the extreme cases of DMD where patients come with the features of cardio respiratory insufficiency. It can be used as a life saving procedure as well.

Other Adjuvant therapies in DMD
1 Use of L carnitine, omega 3 fatty acids & Ubiquinol ( QURANERV-M )
2 Use of Tissue/ Cell regenerators ( Nutristem )
3 Use of Anti inflammatory and neuromuscular regenerators ( Lyprinol)
4 Daflazacort
5 Physical therapy
6 Braces/ Wheel chair
7 Oxygen therapy/ BIPAP

Over all about DMD
Duchenne muscular dystrophy (DMD) is one of the most prevalent neuromuscular disorders, affecting up to 1/3500 male births worldwide . It is caused by mutations in the dystrophin gene on the X chromosome, so it an X- linked recessive disorder, so usually it does not affect girls. Usually symptoms appear at the age of four years. The disease progresses very quickly and usually the patients necessitate a wheelchair by the age of 10 years. The life expectancy can be significantly extended by using Stem cell therapy, corticosteroid treatment and respiratory supports but usually they die by the age of 30 years due to cardio respiratory complications . DMD patients develop a severe cardiomyopathy that generally at about 10 years of age.
Becker muscular dystrophy (BMD) is the milder form of dystrophinopathy, with an incidence of 1 in 18,518 male births. BMD typically presents later than DMD, between ages of 5 and 15 years.The severity or course of disease is better than DMD patients.

Why muscles waste in Duchenne muscular Dystrophy
The essential function of dystrophin in the muscle is to stabilize the fibers during contractions Since DMD is associated with mutations as deletions (65%), duplications (6%–10%), small mutations (10%), or other smaller rearrangements , these mutations lead to loss of dystrophin protein expression resulting in a severe muscle wasting leading to respiratory and cardiac failure and death before the age of 30. Moreover, in DMD patients. The regenerative ability of myofibers is also compromised due to chronic injury that induce satellite cells exhaustion and replacement of muscle with fibro fatty tissue.

Stem cell therapy in DMD as ray of hope for patients.
Since there is no cure available for DMD, and the current interventions are based on prevention and management of complications, the researchers are working hard to develop a possible therapy to reduce both primary and secondary pathologic effects . Here Stem cell therapy has come up in last few years as the ray of hope for DMD patients.