Rejuvenation of the aged Brain and RecoVery of cognitive functions by an already marketed anti-astmatic Drug

INMiND PARTNER Publishes exciting new Research Data

New research published in the Journal Nature Communications shows that Montelukast, an already marketed anti-asthmatic drug, reverts brain aging and loss of cognitive functions in old rodents that have received this drug for 6 weeks at dosages fully compatible with those currently used in patients.

The study, driven and coordinated by Dr. Julia Marschallinger and Professor Ludwig Aigner, Institute of Molecular Regenerative Medicine at the Paracelsus Medical University of Salzburg, Austria, has involved several scientists in Europe (including Professor Maria Abbracchio at the University of Milan, Italy, and Professor Dieter Chichung Lie, University of Erlangen, Germany), and opens concrete perspectives for the treatment of aging-associated neurodegenerative diseases characterized by loss of cognitive functions, memory impairment and dementia. A clinical study to evaluate the beneficial effects of Montelukast in selected populations of patients with cognitive defects is already under design.

Due to increased life expectancy - in Europe nearly 78 years - problems related to cognitive decline and increased incidence of dementia in the elderly represent a dramatic social, economical and health emergency. Counteracting brain inflammation, neuronal dysfunction and aging-associated reduction of neurogenesis in the hippocampus - i.e., the formation of new neurons, which store the information that we learn from the environment,- represents one of the most ambitious challenges of neuro-regenerative medicine aimed at rejuvenating the aged brain and restoring its function.

The study demonstrates that, in old rats, administration of Montelukast -a drug with a very good safety profile and a low incidence of side effects in patients - markedly reduces brain inflammation, restores hippocampal neurogenesis and increases animals' learning and memory abilities back to levels almost identical to those of young rats.

“The rousing idea was that molecular mechanisms that are present in the asthmatic lung could also be present in the brain, in particular in the aged and degenerated brain, and if we block such mechanisms, we might be able to stop brain aging or even rejuvenate the aged brain" explains Aigner.  "Moreover, it has been known for quite a long time that the brain is not secluded from the rest of the body as it was originally believed, and that its function is profoundly influenced by the presence of inflammation in other organs" says Abbracchio. "Ten years ago we anticipated that systemic inflammation -which is, in turn, markedly influenced by both the environment and the diet - can accellerate brain aging and increase the incidence of neurodegenerative diseases like Alzheimer's and Parkinson's" (Marchetti B and Abbracchio MP, Trends Pharmacol Sci, 2005). "In the long run, the presence of inflammation in the periphery" adds Aigner "reduces the ability of the brain to repair itself and increases its deterioration. A previous study directed by Tony Wyss-Coray in Stanford, to which the Aigner group had contributed, had demonstrated that one of the causes of cognitive decline in the old is the accumulation in the blood - and from there, into the brain - of eotaxin, an inflammatory molecule involved in asthma (Villeda et al., Nature, 2011). The clinical studies will confirm if, as expected, Montelukast could represent a successful case of drug "repositioning" extending the use of an already approved drug to therapeutic indications that are different from the original one, thus greatly accellerating the discovery of new therapies for currently incurable human diseases.

Link to original paper:
Marschallinger et al., 2015

Links to the quoted articles:
Marchetti B & Abbracchio MP, 2005

Villeda et al., 2011



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