Study leader professor Jordi Alberch, head of the Consolidated Research Group on Pathophysiology of Neurodegenerative Diseases of the University of Barcelona, said:
“Preclinical results show an improvement of cognitive deficits in Huntington’s disease. Given the safety profile of the drug and the fact that it can also rescue motor deficits in HD mice, the study suggests that fingolimod can be an effective drug to treat Huntington’s disease. We believe it would be worthy to carry out clinical trials in the mid-term.”
Huntington’s disease affects between five and seven subjects out of 100,000 in western countries.
The progressive and irreversible neurodegenerative disorder is caused by a mutation of the gene which codifies the protein huntingtin (HTT). It is a rare hereditary disease which mostly affects basal ganglia and causes bad motor, cognitive and psychiatric disturbances.
Notable advances have been done in basic research on Huntington’s disease. But an effective treatment has still not been found.
The study was conducted by researchers at the University of Barcelona (UB) and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS)
A previous study by the UB-IDIBAPS team found that cognitive and synaptic deficits of Huntington’s disease patients were linked to an imbalance between brain-derived neurotrophic factor (BDNF) receptors TrkB and p75NTR, key factors in synaptic plasticity regulation, cognitive function and memory.
The new study demonstrates that fingolimod (trade name Gilenya) influences these BDNF receptors and re-establishes their normal balance, by increasing TrkB and reducing p75NTR simultaneously. It attenuates over-activation of astrocytes and reduces neuroinflammation, ultimately leading to a better preservation of dendritic spines and memory function.
“Findings constitute a significant step forward in understanding how fingolimod acts on brain cells; it has been proved that it can be an effective drug to treat diseases affecting the hippocampus, like Huntington’s disease and Alzheimer’s disease,” points out Andrés Minguez, researcher in the UB-IDIBAPS research group and first author of the paper. “Findings also open the door for studying cognitive function improvement in sclerosis multiple patients treated with fingolimod; this is an issue that has not been examined in detail yet even if it is estimated to occur in more than 50% of patients.”
Neurodegenerative disease: Could fingolimod provide cognitive benefits in patients with Huntington disease? Nature Reviews Neurology, 2015; DOI: 10.1038/nrneurol.2015.117
Illustration: Hippocampal neurons. Credit A J Irving, Wellcome Images