'There are newer treatment options'

Published : Oct 21, 2005 00:00 IST



Interview with Dr. V. Vedanarayanan, University of Mississippi Medical Centre.

Dr. V. Vedanarayanan, a specialist in paediatric neuromuscular diseases at the University of Mississippi Medical Centre in the United States, graduated from the University of Madras and received postgraduate education at Johns Hopkins University and Duke University in the U.S.

Trained in electromyography (EMG) his clinical and research interests include neuromuscular disorders and paediatric neurology. He has done pioneering research on muscular dystrophy and spinal cord diseases and published extensively in these areas.

Dr. Vedanarayanan was in Chennai recently to deliver the seventh E.S. Krishnamoorthi Memorial Lecture in "Recent Advances in Neurogenetics" organised by Dr. Krishnamoorthi Srinivas, who was recently inducted into the American Academy of Neurology, the largest world body of professional neurologists. Dr. Vedanarayanan spoke to Asha Krishnakumar on the symptoms, diagnosis and treatment options for children with neuromuscular diseases. Excerpts from the interview:

What are the most common neuromuscular diseases among children?

Most children I see are affected by muscular dystrophy, inflammation of muscles, cerebral palsy, motor problems related to injuries at the time of birth or thereafter, and also birth-related injuries to the arms and legs - mostly to the nerves in the arms.

The most common diagnosis would be spasticity in children, muscular dystrophy and different kinds of delays - not walking, crawling, and so on. Other less common problems are spinal muscular atrophy, neuropathies, and so on.

What is the incidence of these diseases and what are the common symptoms?

Spasticity is very common. It occurs in at least 1 per cent of all births. This happens especially if the baby is born premature. There is delay in walking, trouble with muscles, and so on. It leads to stiffness in the arms. Spastic children have arms and legs curled up, and backs curved. They can have cramps and spasms. Some babies may never learn to walk, some may not even talk, and others may have crooked postures when seated. Some of them have epilepsy - a fairly common complication. Mental handicap, retardation and difficulty with learning are all common associated problems. The biggest problem with spasticity is that it leads to bone and other joint deformities, produces painful cramps and spasms and makes it hard for the family to take care of the patients. Sometimes, in a third of those cases, we can, by reducing spasticity, help them to walk, sit and even function better.

Dushean dystrophy [a genetic disease of progressive muscle weakness that leaves children wheelchair-bound and also causes death by the early 20s] occurs probably once in every 3,000-4,000 births. We see four or five new cases every year. This is by far the most devastating of all the neuromuscular diseases in children. These diseases should be occurring at almost the same frequency in India.

What is the role of families in dealing with these diseases?

They must be involved at every stage because management of such diseases is difficult and families play a very important role in it. Families need to be educated. They must be given options and allowed to decide.

What are the latest treatment options and is there any cure for these diseases?

There is a big push to find a cure or at least modify the problems in different ways. There are newer treatment options. First is physical therapy, followed by botulinum toxin injections. For a small set of patients we use medication that is pumped into their spinal fluid. A catheter is put in the spinal fluid and a pump is inserted on the abdominal wall. It constantly pushes a medicine that relaxes the nerve cells so that the muscle tone is maintained. Most children who have had this insertion have had positive results. The important thing is that treatment should be done for the right child, in the right way and managed in the right fashion.

How expensive is this treatment?

It is still expensive. In the U.S., the implantation costs about $15,000 [about Rs.6 lakhs]. It can come down.

What are the other treatment options?

A botulinum toxin injection is the other treatment option. It relaxes the muscle and it is very easy to administer. If you have certain muscle groups that are tight, you can selectively loosen them, without affecting the others. But again, expense is the issue. The cost in the U.S. is $600-700 a bottle.

How many bottles of this toxin should a child be injected with every month?

A child of less than five years may need one every three or four months. This is available in India and is used commonly.

How many of the muscular diseases in children have a genetic base?

Spasticity mostly is acquired from a birth-related complication or trauma. It could even be prenatal - for some reason the brain does not form normally in such cases. Some of them could be from injury, road accidents or after meningitis or encephalitis. These are the most common reasons for spasticity. Dushean is a genetic disease, which is currently treated with oral prednisolone.

Are there treatment options for muscle diseases that are genetically determined?

Yes. We do have treatment for diseases with a genetic base. Now two or three treatment options are being evaluated on humans. We anticipate that within two years the safety of these approaches will be evaluated. Once that happens, treatment options, I think, would open up real fast.

In this country there is a good molecular biology research infrastructure. You have many students trained in it. It probably needs to be directed and similar approaches can be done here. There is no dearth of people who can do it here. It is only a question of getting them interested. There is no problem with funding. Many types of genetic research are under way here. It is only a question of application.

Do these diseases vary across economic, gender, ethnic or geographic conditions?

These diseases are very democratic. They will get everybody the same way. Dushean, of course, exclusively affects boys with very rare exceptions. There are two or three such diseases that are exclusively found in males. But other than that, these diseases can affect anyone and in the same way.

Can none of these diseases be cured?

The approach now is only to modify, change or control them so that they become milder. We use different methods to do so. We are not stuck on replacing the gene and getting it right. We are seeing what else can be done that will work in its place.

Have the genes causing such diseases been identified?

Absolutely. The gene causing Dushean muscular dystrophy was identified in 1987. It is one of the first big ones to be identified. We know exactly what type it is, where it is, why, what and how it works, and also which portion of the protein is more important and so on. Once the portions of the protein that are important are identified, it [the disease] is easier to address; we do not have to insert the entire protein, a small piece is enough.

How many children affected by neuromuscular diseases actually have access to some form of treatment in India?

In India treatment with a steroid [prednisolone] is offered to every child who has Dushean. It is also affordable. The newer treatments are still in various phases of testing and trials. But the important thing is that these trials are already approaching the human phase. They are out of laboratories.

What is the state-of-the-art research in diagnosis and treatment methods?

The one that is in process is called anti-sense nuclear tide therapy. It shuts off a portion of the gene. And when it is shut off, the hope is that when you restart, it will come on right - just like rebooting your computer when it does not work. The gene may not be normal, but some protein will be smaller, shorter and have at least some function. We will have to see how the patients on whom it is tried initially respond. The main thing is to determine what kind of toxicity [it leads to]. This is a really big treatment option, which will change the way we look at these diseases. We are still in the process of trying to reset one part of the gene without disturbing the whole. Once this is achieved we will be right on track to treating these diseases. Treatment is not going to be exclusively gene replacement but all the other methods that work. This makes more sense in the long run. We need something and we are using substitutes to work in its place.

Has pharmacology kept pace with our understanding of these diseases?

All the micro-molecules that are being tested for gene expression are done by pharmacologists. They also grow cell-lines out of patients and expose them to all kinds of medicines. They can very rapidly test a large number of medicines. It is a constant process. Once molecular biology research ascends to that level it blends with pharmacology and you cannot actually differentiate one from the other.

What percentage of recovery is possible in these diseases?

Now they are all degenerative diseases. So, all we can do is slow the progression. But if you have three years today, what happens in these years may lead to completely different options. So you have an extra three years of opportunity.

Are the numbers affected by these diseases falling or increasing?

It is not increasing. This particular gene [dystrophin, which is responsible for these diseases] is very large - it is the largest gene - and thus more susceptible to all kinds of mutations. Because it is too long, there is a frequent crossover. It is spontaneous mutation and is common. You may have nobody in the family with these diseases, but a mother could still have a child with the disease. That is very common. Though they say that it is X-linked, it may be the only gene-line that mutates.

What is the situation in India regarding these diseases?

Dr. Krishnamoorthi Srinivas [on Dr. Vedanarayanan's request]: Treatment options are available in India. With the Internet, most neurologists are also familiar with what is available world over. Gene testing facilities are also available in India. Most important is to counsel the family about the disease and treatment options.

We thus have counsellors, social workers and nurses to educate families. It has to be done slowly. They have to accept it mentally and be prepared for prolonged care and treatment. If the news of the disease is broken to the family abruptly they will go for multiple consultations and not even get proper treatment.

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