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Home Lifestyle Health & Fitness

Treatment of progressive neurological, neuromuscular disorder gets a shot in the arm  

National Age by National Age
February 10, 2022
in Health & Fitness, Science
0
Treatment of progressive neurological, neuromuscular disorder gets a shot in the arm  
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New Delhi, Feb 10: A new treatment could soon be in the offing for Fragile X-associated tremor/ataxia syndrome (FXTAS). Currently, management of the disorder is limited to symptomatic treatment of psychiatric and behavioral problems. 

Patients with the disease, a progressive neurological and neuromuscular disorder, could show several symptoms such as problems in balancing during walking, shaking of hands when grabbing things, memory loss, autonomic dysfunction, cognitive decline, seizure, and Parkinsonism. It affects 1 in 4,000 males and 1in 6,000 to 8,000 females worldwide. It usually begins at the age of 58 to 60 years. 

It is caused by a specific type of mutation in the DNA sequence of a gene called fragile X mental retardation 1 (FMR1). The mutation is named CGG trinucleotide repeat. The number of trinucleotides repeats in FXTAS patients is more than 200 times compared to healthy persons, where it is 55 times. This excess trinucleotide repeats cause cytotoxicity in neuronal cells leading to brain cells degeneration. 

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A team led by Dr. Amit Kumar, Associate Professor and Head, Department of Biosciences and Biomedical Engineering at Indian Institute of Technology (IIT)- Indore has found three chemical compounds that significantly reduce the trinucleotide repeats RNA associated neuronal cells cytotoxicity and restored normal cell viability, in preliminary studies.

The researchers identified the compounds from a library of about 25 lakh small molecules maintained by the National Cancer Institute (NCI), United States of America. This study was conducted in three different steps: shape and chemical-based virtual screening; biophysical analysis of the lead compounds with target RNA; and analysis of the potency of lead molecules using diseased cellular models. 

The lead compounds were tested in both developed cellular models of FXTAS and cell lines isolated from a patient suffering from the disease. Three compounds at the end were found to be selective and specific against CGG repeat RNA. 

Speaking to India Science Wire, Dr. Kumar said, “CGG trinucleotide repeats expansion is involved in the pathogenesis of more than 15 different neurological diseases. We hope our finding would help in developing therapeutics for other diseases too”. 

The study team included Arun Kumar Verma, Eshan Khan, and Subodh Kumar Mishra. They have published a report of their work in the science journal Molecular Neurobiology, Springer. (India Science Wire)

Tags: braincellDNAFragile X-associated tremor/ataxia syndromeFXTASgeneIndian Institute of Technologymemory lossmutationneuronalParkinsonismpsychiatricscreening; biophysicalseizuresequencetreatment
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