Evidence map›Paper›PMID 42137299›Full record

ArticleMolecular therapy. Advances2026

Advancing AADC deficiency therapy through MR-guided multisite delivery of AAV2-hAADC to dopaminergic and serotonergic pathways in the brainstem.

Lluis Samaranch, Clemens Neudorfer, Matthew T Rocco, Allison O'Brien, Vikas Munjal, Nathan McFarland, Meika Travis, Anitvir S Taunque, Kaya E Ceyhan, Akhila Dandamudi and 10 more

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Article in Molecular therapy. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

20 authors.

Lluis SamaranchDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Clemens NeudorferDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Matthew T RoccoDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Allison O'BrienDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Vikas MunjalDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Nathan McFarlandDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Meika TravisDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Anitvir S TaunqueDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Kaya E CeyhanDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Akhila DandamudiDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Ahmad KarkhahDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Abigail NimmoDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
John BringasDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Asad S AkhterDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Brad YoungbloodUniversity Laboratory Animal Resources, The Ohio State University, Columbus, OH 43210, USA.
Lori MattoxUniversity Laboratory Animal Resources, The Ohio State University, Columbus, OH 43210, USA.
R Mark RichardsonDepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA.
John R ForsayethDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Russell R LonserDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
Krystof S BankiewiczDepartment of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.

Funding

Validation of a single-pass surgical trajectory to enable AAV2-hAADC infusion into brainstem and mid-brain in nonhuman primateR21NS117852 · NINDS · OHIO STATE UNIVERSITY · PI BANKIEWICZ, KRYSTOF S · 2020 to 2020
$429k
NINDS NIH HHS R21 NS117852
6 · The paper itself

Abstract

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare and often devastating neurometabolic disorder characterized by impaired synthesis of dopamine, serotonin, and norepinephrine. Affected children present with severe developmental delays, motor dysfunction, autonomic instability, and behavioral symptoms, and current treatments remain largely supportive. Current gene therapy trials for AADC deficiency have demonstrated the safety and tolerability of bilateral AAV2-hAADC infusion into the putamen or midbrain. These approaches have restored dopamine synthesis in the basal ganglia and the limbic systems. However, they have not affected serotonin levels, likely due to the lack of transduction of serotonergic neurons by inadequate coverage of relevant brainstem nuclei. Restoring serotonergic signaling may be critical for improving cognitive and behavioral outcomes, which are still not fully addressed by current dopamine-focused therapies. To address this limitation, we evaluated the safety of a multi-target, magnetic resonance (MR)-guided convection-enhanced delivery strategy in nonhuman primates, administering AAV2-AADC into serotonergic and noradrenergic nuclei in addition to current dopaminergic targets. This broader targeting approach aims to enhance serotonin modulation and restore neuromodulatory balance, with potential benefits for cognitive and behavioral function in children with AADC deficiency undergoing gene therapy.

Indexed as

AADC deficiencyAAV2-hAADCCEDconvection-enhanced deliverydopaminegene therapymonoamine metabolismmulti-target brain deliverynonhuman primatesserotonin

Identifiers

PMID42137299
PMCPMC13148929

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.