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

New Delhi(India Science Wire): 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 1 in 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.
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.
ISW/SP/IIT-INDORE/NEUROLOGY/10/02/2022

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