Evidence map›Paper›PMID 41576655›Full record

ArticleMolecular genetics and metabolism2026

Enzyme replacement therapy for CLN1 batten disease that crosses the blood-brain-barrier.

Renuka Raman, Ben Horst, Zahra Shahrokh, Nader Hatambeygi, Maryam Zare, Magdalena Leszczyniecka, Joshua S Harris, William A Banks, Kim M Hansen, Michelle A Erickson and 1 more

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Article in Molecular genetics and metabolism, 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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0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Renuka RamanCollaborations Pharmaceuticals Inc., Raleigh, NC 27606, USA. Electronic address: renuka@collaborationspharma.com.
Ben HorstSTC Biologics, Inc., 330 Nevada Street, Newton, MA 02460, USA.
Zahra ShahrokhSTC Biologics, Inc., 330 Nevada Street, Newton, MA 02460, USA.
Nader HatambeygiSTC Biologics, Inc., 330 Nevada Street, Newton, MA 02460, USA.
Maryam ZareSTC Biologics, Inc., 330 Nevada Street, Newton, MA 02460, USA.
Magdalena LeszczynieckaSTC Biologics, Inc., 330 Nevada Street, Newton, MA 02460, USA.
Joshua S HarrisCollaborations Pharmaceuticals Inc., Raleigh, NC 27606, USA.
William A BanksGeriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Kim M HansenGeriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
Michelle A EricksonGeriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
Sean EkinsCollaborations Pharmaceuticals Inc., Raleigh, NC 27606, USA.

Funding

Manufacture of an intracerebroventricular Enzyme Replacement Therapy for CLN1 Batten DiseaseSB1NS135733 · NINDS · COLLABORATIONS PHARMACEUTICALS, INC. · PI EKINS, SEAN · 2024 to 2025
$4.0M
Manufacture of an intracerebroventricular Enzyme Replacement Therapy for CLN1 Batten DiseaseR44NS107079 · NINDS · COLLABORATIONS PHARMACEUTICALS, INC. · PI EKINS, SEAN · 2022 to 2023
$3.0M
NINDS NIH HHS R44 NS107079NINDS NIH HHS SB1 NS135733
6 · The paper itself

Abstract

CLN1 Batten disease is caused by mutations in the CLN1 gene which codes for the lysosomal enzyme palmitoyl-protein thioesterase-1 (PPT1). Disease progression is marked by intellectual and motor deterioration, seizures, vision loss, and early mortality. There are no approved treatments for this severe pediatric condition. We describe the development and characterization of recombinant human PPT1 (rhPPT1) suitable for use as a clinical enzyme replacement therapy in CLN1 Batten patients. rhPPT1 displays similar mannose-6-phosphate receptor (M6PR)-dependent uptake kinetics in neuronal cell lines from human, rat and non-human primate but not in mouse cells. rhPPT1 crosses the blood-brain-barrier (BBB) in adult mice which is uncommon for unmodified lysosomal enzymes, and is independent of the M6PR and sialic acid receptors even though analytical characterization of rhPPT1 shows complex M6P and sialic acid containing glycans. Our findings suggest for the first time that intravenous dosing of rhPPT1 may be complementary to other dosing strategies in CLN1 patients and may expand its use for other applications.

Indexed as

Blood-Brain BarrierEnzyme Replacement TherapyMembrane ProteinsNeuronal Ceroid-LipofuscinosesThiolester HydrolasesAnimalsHumansMiceRatsRecombinant ProteinsMembrane ProteinsPPT1 protein, humanRecombinant ProteinsThiolester HydrolasesAn enzyme replacement therapy for CLN1 Batten disease crosses the blood-brain-barrier.BBB penetrationCLN1 battenEnzyme replacement therapyLysosomal storage diseasesOne Sentence Summary.Ultra rare diseases

Identifiers

PMID41576655
PMCPMC12928006

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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.