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Unravelling relationship of defective genes

By M. Dinesh Varma

Wojtek Rakowicz, Consultant Neurologist, Hillingdon Hospital, U.K.

CHENNAI, SEPT. 19. Unravelling the inter-relationship between defective genes and a set of complementing genes holds the key to understanding the pathogenesis of Motor Neuron Diseases (MND) and generating improved treatment modalities, says Wojtek Rakowicz, Consultant Neurologist, Hillingdon Hospital, U.K.

"We now know that it is not only the defective genes that are important but a whole set of other genes which can ameliorate the severity of the condition. At the laboratory level, this opens up the option of designing drugs that boost the functioning of these complementing genes to bring down the severity of disorder," said Dr. Rakowicz.

Dr. Rakowicz is in Chennai as a visiting faculty to select institutions in South India as part of an exchange programme between India and the U.K. in neurology. He visited the Institute of Neurology, the Madras Medical College, the T.S. Srinivasan Centre for Neurosciences at the Voluntary Health Services, the Christian Medical College, Vellore and the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Thiruvananthapuram.

Causative genes

Though the exact cause of MNDs is yet to be ascertained, advances in genetics have identified around a dozen causative genes, some of which were responsible for serious conditions and others for mild states of illness.

Modern research is focussed on gaining a better understanding of the genetic context shared by causative and complementing genes, said Dr. Rakowicz. Identifying new mutated genes became crucial to the advancement of treatment for these disorders. Every time a new causative gene was found it opened a new window of insight, he said.

"The Human Genome Project has identified most of the genes in humans but there is still no great understanding of the dynamics of gene functioning. It is like reading the words but not understanding the meaning. Genetic mutation (malfunctioning) holds the key to our understanding of the functioning of genes," said Dr. Rakowicz.

Motor neuron diseases are progressive, degenerative disorders that affect nerves in the upper or lower parts of the body. Some of the diseases are inherited, while others may be acquired. Common MNDs include Amyotrophic Lateral Sclerosis (ALS), Progressive Muscular Atrophy and Postpolio Syndrome.

MNDs are associated with progressive muscle weakness, breathing and swallowing difficulty, limb weakness and slurred speech though the intellect remains intact. At present, treatment of MNDs involve use of the drug Riluzole which slightly delayed the progression of disease.

According to the visiting neurologist, it is important for clinicians to look for new disease entities in MNDs, which could generate greater understanding of the causative genes and thereby improve treatment modalities. "Diseases occur where the people are and not where premier institutions are located. Clinicians do not need fancy machines or sophisticated laboratories and require instead only a set of good clinical skills to identify disease entities".

According to Dr. Rakowicz, neurologists, in a way, mediated between scientists and patients in their task of identifying disease entities and referring them to scientists from whom future treatments emerge.

On his exposure to clinical practice in South India, Dr. Rakowicz said the neurological thinking here was on a par with international standards. Noting the dearth of post DM fellowships, Dr. Rakowicz said it would benefit both India and the U.K. if post DM sub-speciality fellowships were started.

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