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Aline Milane1, Sarah Vautier, Hélène Chacun

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Riluzole, an ALS drug, is transported by breast cancer resistance protein (BCRP) across the blood-brain barrier. This interaction may affect drug efficacy and warrants consideration in clinical trials.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease.
  • Effective ALS treatments require crossing the blood-brain barrier (BBB).
  • Riluzole is the only approved drug for ALS, necessitating understanding its transport mechanisms.

Purpose of the Study:

  • To investigate if riluzole is a substrate for breast cancer resistance protein (BCRP).
  • To determine riluzole's effect on BCRP expression and activity at the BBB.
  • To assess potential drug-drug interactions involving riluzole and BCRP.

Main Methods:

  • Studied riluzole brain transport in CF1 mdr1a (-/-) mice.
  • Assessed intracellular uptake of riluzole in BeWo cells.
  • Evaluated BCRP expression and activity using prazocin as a probe.

Main Results:

  • BCRP inhibition increased riluzole uptake in mice and BeWo cells.
  • Repeated riluzole doses increased BCRP activity in mice.
  • Riluzole enhanced BCRP expression and activity in BeWo cells.

Conclusions:

  • Riluzole is transported by BCRP at the BBB.
  • Riluzole can enhance BCRP function.
  • Potential drug-drug interactions at the BBB involving riluzole and BCRP substrates should be considered for ALS clinical trials.