Dystrophy R&D Lab Inaugurated in Bangalore

Ravdeep Singh Anand’s quest for finding a cure for his son, Karanveer’s muscular dystrophy is coming to fruition with the inauguration of the Dystrophy Annihilation Research Trust’s (DART) Research & Development Centre in Bangalore. The R & D Centre was inaugurated on 27^th July 2015 by Shree. U.T Khader, Minister for Health & Family Welfare, Government of Karnataka. The lab’s in-vitro testing facility was inaugurated by Prof. Steve Wilton, Director of the Western Australian Neuroscience Research Institute. The DART lab has a world-class clean room environment for hosting cell culture and in-vitro and bio-banking facilities. Dr. Arun Shastry is the Chief Scientific Officer, who has a keen interest in innovative therapeutic approaches to find a cure for muscular dystrophy.

The idea of setting up a lab to host innovative R&D work for muscular dystrophy came about in 2010 when Anand contacted Dr Steve Wilton. Dr Wilton was working on a novel research approach to limiting the muscle damage and injury in muscular dystrophy through a procedure known as exon skipping. In exon skipping, sections of the genetic code (exons) are skipped to enable production of functional dystrophin.

In boys with Duchenne Muscular Dystrophy (DMD), degeneration of skeletal muscles is due to absence of dystrophin, a protein essential for preserving muscle mass and enabling smooth muscle movement. In Dr Wilton’s approach, the in-vitro cultured cell lines (obtained through skin biopsy) indicated dystrophin production. The compound he used to enable dystrophin production is called anti-sense oligonucleotides (AONS). AONS enable the muscle fibers to ignore the faulty parts of the genetic code for dystrophin production.

The Lab’s Research

According to Anand, the lab will now focus on in-vitro development of cell lines for about 14 children with muscular dystrophy. The cell lines will be created using muscle and skin biopsies. Muscle biopsy will be done using the painless needle biopsy procedure where the fibroblasts will be aspirated through a needle. The lab now has experts specializing in this painless procedure. The cell lines will be used to determine the amount of dystrophin being produced and calculate the required amount. Since each child presents with a different genetic mutation, it is essential to establish the cell line to determine the right amount of dystrophin needed.

The lab will conduct in-vitro culture using the AONS (compound) to produce dystrophin. Currently, the lab is getting the compound from other agencies but soon they hope to produce the compound themselves using expertise and knowledge from established agencies. In muscular dystrophy, the right amount of dystrophin will prevent further degeneration of skeletal muscles. If the lab can show successful research with the in-vitro dystrophin production, they can go ahead and apply to ICMR (Indian Council of Medical Research) for permission to conduct in-vivo research. Anand is clear about the lab’s two significant principles, “safety” and “efficacy.” The lab will use safe, non-toxic compounds to produce dystrophin. Anand believes that with their current research they will be able to tackle most mutations of muscular dystrophy.

What is Muscular Dystrophy?

Muscular dystrophy is a group of muscular disorders which cause degeneration and progressive loss of muscle mass. Abnormal mutations caused by genes lead to low or non-production of the proteins (dystrophin) required in keeping muscles healthy. Muscular dystrophy is also caused when some exons on the DNA get deleted, duplicated or shifts exons in the strand.

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There are different genotypes of muscular dystrophy caused by various gene mutations:

• Duchenne muscular dystrophy (DMD)
• Becker
• Limb girdle
• Facioscapulohumeral
• Congenital
• Myotonic

The most common and severest form of muscular dystrophy is DMD. This is an X-linked disorder surfacing in 1 among 3500 live male births. Females are usually the carriers. Children with DMD show signs and symptoms as early as 12 months as they struggle to achieve common milestones like sitting up and attempting to stand and walk. Most children gradually lose the ability to walk. Scoliosis or curvature of the spine is also common. Many children develop respiratory issues and some progress to a ventilator state.

Muscular dystrophy is usually diagnosed when blood tests indicate high levels of CPK (creatine phosphokinase). A DNA analysis is also done along with a muscle biopsy if needed.

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There is no cure for muscular dystrophy, but therapeutics like exon skipping can at least halt further degeneration and prevent complications.

About DART (Dystrophy Annihilation Research Trust)

DART was established in 2012 with the idea of providing support to affected children and their families in dealing with muscular dystrophy. Anand is the founder of DART, current President and the driving force behind the organization.

Some of the objectives of the organization are:

• Providing information about muscular dystrophy
• Raising awareness about the disorder
• Working to create access and inclusion in education, employment and public places
• Working towards research for “orphan” diseases
• Counseling support for children and families
• Medical advisory and rehabilitation support
• Assistance to families on tax concession provided by the Government of India
• Collaborate with NGOs to raise awareness about the needs of children with disabilities
• Organizing and coordinating meetings and conferences on muscular dystrophy

The setting up of the R&D lab holds out much hope for children with muscular dystrophy. Families can take comfort in the fact that critical research is being carried out within their reach. Though international research is in progress, not everybody can get access to such research. The lab is much needed to provide critical intervention in muscular dystrophy.

References:

1. http://community.parentprojectmd.org/forum/topics/dystrophy-annihilation-research-trust-india

2. http://www.ninds.nih.gov/disorders/md/md.htm

3. http://www.ncbi.nlm.nih.gov/pubmed/23528047

4. https://www.mda.org/disease/duchenne-muscular-dystrophy/research

5. http://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/basics/definition/con-20021240

Source-Medindia