A scratch on skin, a hug to my son, combing my hair, raising up from my chair, lifting a glass to sip water/tea, a walk on road, wiping a tear from my eye, lighting a diya – all of this seems so trivial an activity yet can be extremely challenging for a person affected by muscular dystrophy like me. I am a 42- year-old married woman, suffering from dysferlinopathy, a form of Limb-Girdle Muscular Dystrophy (LGMD2B), for last 20 years. These limitations and many more are severely impacting, my quality of life and lakhs of many more, making it worse, day by day. Whatever limited set of activities I am able to do at present, and that includes writing this article, I may not be able to do in future.

Muscular dystrophy is a group of rare genetic diseases that cause progressive weakness and loss of muscle mass over the years. Muscular dystrophies are caused by genetic mutations that interfere with the production of muscle proteins that are needed to build and maintain healthy muscles. Early symptoms include a wadding gait, pain and stiffness in muscles, difficulty sitting up or standing, walking on toes, frequent falls etc.

Most common and severe form of muscular dystrophy is Duchenne Muscular Dystrophy (DMD) which typically affects young boys. Less severe is Becker Muscular Dystrophy (BMD) which is similar in symptoms but is milder and progresses more slowly. It is estimated that every year there are over 1,600 children born with DMD in India.

Yet another large group of muscular dystrophies that usually strike during adulthood is Limb-Girdle Muscular Dystrophies. LGMDs are a group of rare neuromuscular diseases that are inherited and cause muscle weakness and wasting similar to other dystrophies. More than 34 forms of LGMDs exist with new forms being discovered each year. Some LGMDs have dominant Inheritance (D) and some have a recessive inheritance(R) pattern. Muscles most affected are closest to the body (proximal muscles), including muscles of shoulders, arms, pelvic area, thighs.

The diagnosis of DMD is relatively easier than LGMDs as DMD has been known to affect young boys (onset 3-5 years old). A primary diagnosis via blood test to check CPK levels along with clinical examination followed by an MLPA test can confirm the diagnosis. MLPA (Multiplex Ligation-dependent Probe Amplification) is a multiplex PCR method detecting abnormal copy numbers of up to 50 different genomic DNA or RNA sequences, which is able to distinguish sequences differing in only one nucleotide. This test costs anywhere between Rs 3000 to Rs 7000.

Diagnosis of LGMDs, along with their subtypes, requires a comprehensive series of clinical examinations including CPK testing followed by genetic testing via Next Generation Sequencing (NGS) technology of DNA extracted from blood samples of Muscular Dystrophy afflicts. Unless whole-genome tests are carried out using NGS, LGMDs are very difficult to diagnose. Also, these diagnostic tests are not affordable by the common man. They cost anywhere between Rs 40,000-50,000. All across India, there are just 5-6 laboratories offering these tests. In the diagnostic workup of suspected LGMD in India, after biochemistry and electrophysiology tests, muscle biopsy is often performed. It is done to establish the dystrophic nature of the process and to rule out alternative causes of muscle weakness. Hence for a confident diagnosis of an LGMD subtype, it is preferable to study all available immunostains, quantitate them by western blotting and also study the genes. To avoid invasive muscle biopsies, Genetic Testing is the most efficient diagnostic tool to identify LGMDs.

LGMDs are categorised according to the defective gene corresponding to the loss of production of protein made by that particular gene. For instance, if a protein Calpain is missing in a person, due to defective gene CAPN3, he is known to have Calpainopathy or LGMD2A. Similarly, if Dysferlin protein is missing in a person due to defective gene DYSF, he is known to have Dysferlinopathy or LGMD2B. According to a recent study with hospital-based data regarding the prevalence of LGMD phenotypes names, it seems that Dysferlinopathy, Calpainopathy and other myopathies like GNE myopathy are common LGMDs in India. LGMDs are the most common adult-onset muscular dystrophy encountered in our country.

I was ironically lucky to have been genetically diagnosed by an International NGO working towards a cure for specifically my subtype, LGMD2B/ dysferlinopathy. But there are lakhs of muscular dystrophy afflicts in India who remain undiagnosed and need proper genetic testing to ascertain their subtypes of LGMDs. According to an article published by Dr Satish Khadilkar in Neurology India, “Due to the complexity of LGMD genetics, it seems to have lagged behind other common neuromuscular disorders. Due to the heterogeneity of LGMD and the lack of diagnostic specificity, estimates of prevalence for all forms of LGMD have ranged from 1 per 14,500 to 1 per 1,23,000 populations. In the Indian setting, it is difficult to know the exact prevalence. In a hospital-based survey in a neuromuscular clinic in Mumbai, approximately one-fourth of all Muscular Dystrophy afflicts had LGMD. In adulthood, LGMD formed the most common diagnosis in the group of muscular dystrophies.”

Worldwide, there are patient registries for specific subtypes to seek information, education about the disease, participate in forums and learning about studies and clinical trials.

The need of the hour is to efficiently manage those afflicted with Muscular Dystrophy with utmost care and compassion. Regular checkups for cardio functions, pulmonary functions along with Physiotherapy including stretching and strengthening exercises must be done. A combination of a healthy diet coupled with regular exercises and dietary supplements for calcium, magnesium, vitamins, etc go a long way to help preserve muscle mass and mobility.

In wake of recent developments in the domain of genetic therapies as a cure for these genetic disorders, there is a strong and urgent need for all muscular dystrophy patient bodies, muscular dystrophy associations and NGOs working for muscular dystrophy afflicts to come together on one platform and collectively address the needs of muscular dystrophy afflicts cohesively. For example, a recent initiative, Parent Project Muscular Dystrophy, brings together parents of children affected by muscular dystrophy.

The priority is to build and maintain a strong database which will enlist all kinds of dystrophies across India. To initiate this drive we are trying to collect patient data from various sources such as different WhatsApp groups running across different states, state-level associations and many more sources including direct registrations. Our attempt is to generate a nationwide patient registry for muscular dystrophies for:

a) Approaching scientific community for clinical studies
b) Government for policy decisions and
c) Organisations for raising funds to support clinical studies

We need strong patient advocacy disease-specific groups to create awareness about all forms of muscular dystrophies. Together we must all integrate to build a single platform with a strong objective to eradicate muscular dystrophy and achieve higher goals.

Emerging therapeutic strategies for cure of muscular dystrophies include:

Pharmacological/Molecular drug therapies: In India, few organisations have been relentlessly working towards finding a cure for killer muscular dystrophies mainly DMD using small molecules to manipulate genes to either halt the progression of the disease and/or reverse the disease. These drugs are fast moving towards clinical trials and are as promising as gene replacement therapies.

Studies are also being carried out in the world to evaluate the efficacy and safety of drugs that are believed to induce the muscle repair process which may prevent or repair muscle damage in muscular dystrophy.

Gene therapies: Gene therapy is a way to treat a disease changing gene expression it has been studied for 40 years and can help stop slow the effects of the disease. Gene therapy is the introduction, removal or change in genetic material specifically DNA or RNA into the cells of a patient to treat a particular disorder. The transferred genetic material changes how a protein/ group of proteins is/are produced by the cell. This new genetic material (healthy gene) is delivered into the cell by using viral vectors such as Adeno Associated Virus vectors. One such study is being carried out by Dr Arka Shubhra Ghosh for the first time for DMD, GROW laboratory, Narayana Nethralaya, Bengaluru. Dr Ghosh, in his post-doctoral in US, developed gene therapy systems using AAV vectors for DMD. He has also been instrumental in formulating national guidelines for use of gene therapy in India.

Gene editing: An ideal approach would be to repair harmful DNA through a combination of gene therapies including genome editing procedure that would alter Muscular Dystrophy afflicts’ genetic code with the CRISPR- Cas9 “molecular scalpel” permanently and directly reverse the cause of a disease. Scientists in Delhi based Institute of Genomics and Integrative Biology (IGIB) of the Council of Scientific and Industrial Research (CSIR) have developed a new variant of currently popular gene-editing CRISPR Cas 9. They have shown that this variance can increase precision in editing genome while avoiding unintended changes in DNA.

As we look ahead, we should involve stakeholders such as government policymakers, scientific community including researches scientists, clinicians, hospitals, patient groups, and NGOs to come forward together to find effective and safe solutions for all of us Muscular Dystrophy Muscular Dystrophy afflicts.

(Gitika Khanna has been living with muscular dystrophy for the last 20 years)

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Views expressed above are the author's own.

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