Principal Investigators

    Dr Riccardo Brambilla


    Cardiff University

    Contact information of lead PI


    United Kingdom

    Title of project or programme

    Testing a combination therapy with Ras-ERK and mTor inhibitors for L-DOPA induced dyskinesia

    Source of funding information

    Parkinson's UK

    Total sum awarded (Euro)

    € 203,370

    Start date of award


    Total duration of award in years



    Research Abstract

    L-DOPA remains the most effective treatment for alleviating Parkinson’s disease (PD) symptoms but causes currently untreatable severe motor side effects, collectively known as levodopa-induced dyskinesia (LID). Recent evidence indicates that a key pathogenic factor for LID, linked to abnormally high dopamine-mediated responses, is the hyperactivation in the striatum of both the Ras-ERK and the mTor signalling pathways. Previous work by the applicant, funded by Parkinson’s UK, identified a clinically relevant Ras-ERK inhibitor that, given systemically, is not only able to block cell signalling in a mouse model of PD and LID but also to partially revert already established dyskinesia. Since the inhibition of LID with maximal doses of this Ras-ERK inhibitor is incomplete, we hypothesise that a combination approach with a selected mTor inhibitor may provide a better therapeutic outcome. Hence, in this project we will test 5 distinct mTor inhibitors, already in advanced stage of clinical development for cancer treatment, for their ability to prevent in mice abnormal involuntary movements (AIMs), the rodent correlate of LID.

    Further information available at:

Types: Investments < €500k
Member States: United Kingdom
Diseases: N/A
Years: 2016
Database Categories: N/A
Database Tags: N/A

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