Evidence map›Paper›PMID 41404412›Full record

ArticleMolecular therapy. Methods & clinical development2025

Inhibition of immune response reduces pathology in dorsal root ganglia and peripheral nerves in cynomolgus macaques following AAV gene therapy.

Branka Grubor, Kate L Henry, Su Jing Chan, Mark Sheehan, Anumeha Shah, Alex Pellerin, Judy Bai, Prasad Nadella, Santhosh Bommegowda, Patrick Cullen and 33 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Intra-CNS AAV9-Molecular therapy. Advances · 2026
    Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors.

Branka GruborBiogen, Cambridge, MA 02142, USA.
Kate L HenryBiogen, Cambridge, MA 02142, USA.
Su Jing ChanBiogen, Cambridge, MA 02142, USA.
Mark SheehanBiogen, Cambridge, MA 02142, USA.
Anumeha ShahBiogen, Cambridge, MA 02142, USA.
Alex PellerinBiogen, Cambridge, MA 02142, USA.
Judy BaiBiogen, Cambridge, MA 02142, USA.
Prasad NadellaBiogen, Cambridge, MA 02142, USA.
Santhosh BommegowdaBiogen, Cambridge, MA 02142, USA.
Patrick CullenBiogen, Cambridge, MA 02142, USA.
Eric TienBiogen, Cambridge, MA 02142, USA.
Vivian ChenCharles River Laboratories, Durham, NC 27703, USA.
Nicholas P van der MunnikBiogen, Cambridge, MA 02142, USA.
Stephanie White-HuntCharles River Laboratories, Durham, NC 27703, USA.
Edward D PloweyBiogen, Cambridge, MA 02142, USA.
Stefan HamannBiogen, Cambridge, MA 02142, USA.
Amanda J GuiseBiogen, Cambridge, MA 02142, USA.
Shanqin XuBiogen, Cambridge, MA 02142, USA.
Melissa KirklandBiogen, Cambridge, MA 02142, USA.
Jessica DohertyBiogen, Cambridge, MA 02142, USA.
Eugenia LyashenkoBiogen, Cambridge, MA 02142, USA.
Guruharsha BhatBiogen, Cambridge, MA 02142, USA.
Kelly GlajchBiogen, Cambridge, MA 02142, USA.
Shih-Ching LoBiogen, Cambridge, MA 02142, USA.
Davide GianniBiogen, Cambridge, MA 02142, USA.
Pete ClarnerBiogen, Cambridge, MA 02142, USA.
Jake GagnonBiogen, Cambridge, MA 02142, USA.
Jenhwa ChuBiogen, Cambridge, MA 02142, USA.
Kalyani NambiarBiogen, Cambridge, MA 02142, USA.
Mukesh LullaBiogen, Cambridge, MA 02142, USA.
Fengmei ZhengBiogen, Cambridge, MA 02142, USA.
Asmerom WeldeabBiogen, Cambridge, MA 02142, USA.
Dan BartlettBiogen, Cambridge, MA 02142, USA.
Amos GutnickBiogen, Cambridge, MA 02142, USA.
Taylor ReynoldsBiogen, Cambridge, MA 02142, USA.
Kan ZhuBiogen, Cambridge, MA 02142, USA.
Dann HuhBiogen, Cambridge, MA 02142, USA.
Thomas M CarlileBiogen, Cambridge, MA 02142, USA.
James FikesBiogen, Cambridge, MA 02142, USA.
Patrick TrapaBiogen, Cambridge, MA 02142, USA.
Junghae SuhBiogen, Cambridge, MA 02142, USA.
Dale MorrisBiogen, Cambridge, MA 02142, USA.
Linda BurklyBiogen, Cambridge, MA 02142, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Administration of adeno-associated virus (AAV) gene therapies via blood or cerebrospinal fluid (CSF) in non-human primates (NHPs) can lead to degeneration of dorsal root ganglion (DRG) neurons and nerve fibers in the spinal cord and peripheral nerves. AAV cargo expression is implicated in AAV DRG toxicity, but the underlying mechanism(s) is unknown. Here, we performed a time course study of intra-cisterna magna (ICM) administration of an AAV9 variant encoding human survival of motor neuron 1 (hSMN1) to identify molecular and cellular changes preceding pathology. Increases in inflammatory gene modules, cerebrospinal fluid (CSF) cytokines, and immune cell infiltrates as early as day 5 prior to neuron and nerve fiber degeneration on days 15 and 29 suggested a role for the immune response in AAV-mediated toxicity. Prophylactic treatment with a glucocorticoid steroid dexamethasone and a calcineurin inhibitor tacrolimus diminished pathology in NHPs following administration of three AAV gene therapy vectors. Collectively, these data demonstrate a causal role for the immune response to AAV in AAV-mediated DRG and nerve fiber toxicity. The efficacy of immunosuppression with three different AAV cargos suggests broad utility across AAV vectors and provides a clinically feasible approach to mitigating this potential toxicity in patients.

Indexed as

AAVAAV gene therapyadeno-associated virusdorsal root ganglion (DRG) toxicityimmunosuppressionNHPnonhuman primate

Identifiers

PMID41404412
PMCPMC12704302

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Registered trials

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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.