Evidence map›Paper›PMID 25322757›Full record

Trial reportMolecular therapy : the journal of the American Society of Gene Therapy2015

A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy.

Jerry R Mendell, Zarife Sahenk, Vinod Malik, Ana M Gomez, Kevin M Flanigan, Linda P Lowes, Lindsay N Alfano, Katherine Berry, Eric Meadows, Sarah Lewis and 10 more

3 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 147 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 3 pooled it
10.0field-weighted citation impact, top 1% of its field
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.

NCT01519349 phase1completednot on this map

Phase I Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis.

TypeinterventionalSponsorNationwide Children's HospitalRan2012 to 2017Enrolled15ConditionsBecker Muscular Dystrophy, Sporadic Inclusion Body MyositisArmsrAAV1.CMV.huFollistatin344
NCT02354781 phase1 / phase2completednot on this map

Phase I/II Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344 Trial to Patients With Duchenne Muscular Dystrophy

TypeinterventionalSponsorJerry R. MendellRan2015 to 2017Enrolled3ConditionsDuchenne Muscular DystrophyArmsrAAV1.CMV.huFollistin344
NCT07443826 phase1 / phase2recruitingnot on this mapstarted 2026, after this paper: background citation

CALM-AF-AI: Counteracting Age-related Loss of Muscle With AAV-Follistatin Combined With Angiogenesis-Inducing VEGF Plasmid Gene Therapy

TypeinterventionalSponsorUnlimited Biotechnology LLCRan2026 to 2028Enrolled12ConditionsAge-related Muscle DeclineArmsAAV9-Follistatin gene therapy, VEGF Plasmid
3 · Its place in the literature

Who cites it

147 citing papers in PubMed, 3 syntheses or guidelines pooled it, 229 citations in OpenAlex.

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87 more citing papers are in PubMed but not listed here.

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

20 authors at 2 institutions in 1 country.

Jerry R Mendell1] Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA [2] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA [3] Department of Neurology, The Ohio State University, Columbus, Ohio, USA.
Zarife Sahenk1] Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA [2] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA [3] Department of Neurology, The Ohio State University, Columbus, Ohio, USA.
Vinod MalikCenter for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Ana M GomezCenter for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Kevin M Flanigan1] Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA [2] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA [3] Department of Neurology, The Ohio State University, Columbus, Ohio, USA.
Linda P Lowes1] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA [2] Department of Physical Medicine and Rehabilitation, The Ohio State University, Columbus, Ohio, USA.
Lindsay N Alfano1] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA [2] Department of Physical Medicine and Rehabilitation, The Ohio State University, Columbus, Ohio, USA.
Katherine Berry1] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA [2] Department of Physical Medicine and Rehabilitation, The Ohio State University, Columbus, Ohio, USA.
Eric MeadowsCenter for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Sarah LewisCenter for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Lyndsey BraunCenter for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Kim ShontzCenter for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Maria RouhanaCenter for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Kelly Reed Clark1] Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA [2] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
Xiomara Q Rosales1] Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA [2] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
Samiah Al-Zaidy1] Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA [2] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
Alessandra GovoniCenter for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Louise R Rodino-Klapac1] Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA [2] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
Mark J HoganDepartment of Radiology, Vascular and Interventional Radiology, Nationwide Children's Hospital, Columbus, Ohio, USA.
Brian K Kaspar1] Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio, USA [2] Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
Nationwide Children's Hospital · USThe Ohio State University · US

Funding

Training and Education CoreU54HD066409 · NICHD · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI MARTIN, PAUL TAYLOR · 2010 to 2014
$6.7M
NICHD NIH HHS 5U54HD066409-05NICHD NIH HHS U54 HD066409
6 · The paper itself

Abstract

Becker muscular dystrophy (BMD) is a variant of dystrophin deficiency resulting from DMD gene mutations. Phenotype is variable with loss of ambulation in late teenage or late mid-life years. There is currently no treatment for this condition. In this BMD proof-of-principle clinical trial, a potent myostatin antagonist, follistatin (FS), was used to inhibit the myostatin pathway. Extensive preclinical studies, using adeno-associated virus (AAV) to deliver follistatin, demonstrated an increase in strength. For this trial, we used the alternatively spliced FS344 to avoid potential binding to off target sites. AAV1.CMV.FS344 was delivered to six BMD patients by direct bilateral intramuscular quadriceps injections. Cohort 1 included three subjects receiving 3 × 10(11) vg/kg/leg. The distance walked on the 6MWT was the primary outcome measure. Patients 01 and 02 improved 58 meters (m) and 125 m, respectively. Patient 03 showed no change. In Cohort 2, Patients 05 and 06 received 6 × 10(11) vg/kg/leg with improved 6MWT by 108 m and 29 m, whereas, Patient 04 showed no improvement. No adverse effects were encountered. Histological changes corroborated benefit showing reduced endomysial fibrosis, reduced central nucleation, more normal fiber size distribution with muscle hypertrophy, especially at high dose. The results are encouraging for treatment of dystrophin-deficient muscle diseases.

Indexed as

AdultDependovirusDystrophinFollistatin-Related ProteinsGene ExpressionGenetic TherapyGenetic VectorsHumansInjections, IntramuscularMaleMuscle, SkeletalMuscular Dystrophy, DuchenneMyostatinDMD protein, humanDystrophinFollistatin-Related ProteinsMSTN protein, humanMyostatin

Identifiers

PMID25322757
PMCPMC4426808
OpenAlexW2039035739

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.