AUTHOR=Giordano Antonino , Clarelli Ferdinando , Cannizzaro Miryam , Mascia Elisabetta , Santoro Silvia , Sorosina Melissa , Ferrè Laura , Leocani Letizia , Esposito Federica 

TITLE=BDNF Val66Met Polymorphism Is Associated With Motor Recovery After Rehabilitation in Progressive Multiple Sclerosis Patients

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.790360

DOI=10.3389/fneur.2022.790360

ISSN=1664-2295

ABSTRACT=<sec><title>Background</title><p>Rehabilitation is fundamental for progressive multiple sclerosis (MS), but predictive biomarkers of motor recovery are lacking, making patient selection difficult. Motor recovery depends on synaptic plasticity, in which the Brain-Derived Neurotrophic Factor (BDNF) is a key player, through its binding to the Neurotrophic-Tyrosine Kinase-2 (NTRK2) receptor. Therefore, genetic polymorphisms in the BDNF pathway may impact motor recovery. The most well-known polymorphism in <italic>BDNF</italic> gene (rs6265) causes valine to methionine substitution (Val66Met) and it influences memory and motor learning in healthy individuals and neurodegenerative diseases. To date, no studies have explored whether polymorphisms in <italic>BDNF</italic> or <italic>NTRK2</italic> genes may impact motor recovery in MS.</p></sec><sec><title>Objectives</title><p>To assess whether genetic variants in <italic>BDNF</italic> and <italic>NTRK2</italic> genes affect motor recovery after rehabilitation in progressive MS.</p></sec><sec><title>Methods</title><p>The association between motor recovery after intensive neurorehabilitation and polymorphisms in <italic>BDNF</italic> (rs6265) and <italic>NTKR2</italic> receptor (rs2289656 and rs1212171) was assessed using Six-Minutes-Walking-Test (6MWT), 10-Metres-Test (10MT) and Nine-Hole-Peg-Test (9HPT) in 100 progressive MS patients.</p></sec><sec><title>Results</title><p>We observed greater improvement at 6MWT after rehabilitation in carriers of the <italic>BDNF</italic> Val66Met substitution, compared to <italic>BDNF</italic> Val homozygotes (<italic>p</italic> = 0.024). No significant association was found for 10MT and 9HPT. <italic>NTRK2</italic> polymorphisms did not affect the results of motor function tests.</p></sec><sec><title>Conclusion</title><p><italic>BDNF</italic> Val66Met was associated with walking function improvement after rehabilitation in progressive MS patients. This result is in line with previous evidence showing a protective effect of Val66Met substitution on brain atrophy in MS. Larger studies are needed to explore its potential as a predictive biomarker of rehabilitation outcome.</p></sec>