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      4-Phenylbutyrate for SLC6A1-Meaningful Outcomes and Access : A case for repurposing Phenylbutyrate (ATX-018) to include use in the treatment of SLC6A1 and additional rare indications

      Published
      conference-abstract
        1 , 2 , , 3 , 4
      RExPO23 Conference
      REPO4EU
      RExPO23
      25-26 October 2023
      SLC6A1, Epilepsy, Neurodevelopmental Disorders, GABA, GAT-1, Phenylbutyrate, Drug repurposing, Drug trial, Meaningful outcome
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            Abstract

            IntroductionThe clinical picture of SLC6A1 gene mutations is characterised by a mild-to-moderate intellectual disability, speech difficulties, behavioural problems, epilepsy characterizing a myoclonic-atonic epilepsy (MAE), and neurological signs (1).

            Backgroundo J. Kang has shown that 4-phenylbutyrate improves the function and trafficking of GAT-1 (2)o Glyceryl Phenylbutyrate (Ravicti®) is a prodrug and approved for use ONLY in treating children with urea cycle disorder.o Ravicti ® currently costs around $793,632 for a year of treatment in the US (3)

            SLC6A1connect has financially supported the following research:• Study of 4-phenylbutyrate (PBA) rescue of SLC6A1 mutation-mediated disorders in patient derived cell and mouse models (4)• Open Label Trial,in SLC6A1 and STXBP1 patients for which the fully analysed published results are pending (5)• Preliminary results showed SLC6A1 patients that had seizures all saw a significant response in seizure activity with reductions from 50% (n=1) to 90% (n=4), to seizure freedom (n=1), at 10 weeks from baseline (as did STXBP1).

            DiscussionThe impact on quality of life is its real meaningful outcome. As numbers on Ravicti® increase, families report significant improvements in sleep, mood, behaviour, aggression, cognition, articulation, focus and of course seizure burden.

            What next?

            Full analysis of the trial to be published

            Obtain new sources of phenylbutyrate - Aayam Therapeutics has identified an alternate patentable drug – ATX-018. SLC6A1 and Aayam are raising investment through sources that would also allow this to be affordable for patients globally.

            Support in the repurposing of Phenylbutyrate (ATX-018) to include use in the treatment of SLC6A1, and access for families

            Content

            Author and article information

            Conference
            RExPO23 Conference
            REPO4EU
            21 September 2023
            Affiliations
            [1 ] SLC6A1 Connect, UK;
            [2 ] arthursquest.org UK;
            [3 ] Aayam Therapeutics, San Jose, CA, USA;
            [4 ] SLC6A1 Connect, 8700 Stonebrook Parkwa, Suite 51 Frisco, TX 75034 USA;
            Author notes
            Author information
            https://orcid.org/0009-0000-0381-0998
            Article
            10.58647/REXPO.23000026.v1
            da0471f6-dde3-496e-bde8-2d70c46821d5

            This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

            RExPO23
            2
            Stockholm, Sweden
            25-26 October 2023
            History
            : 21 September 2023
            Categories

            Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
            Medicine
            SLC6A1,Epilepsy,Neurodevelopmental Disorders,GABA,GAT-1,Phenylbutyrate,Drug repurposing,Drug trial,Meaningful outcome

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