1. Muscle Nerve. 2014 Oct;50(4):477-87. doi: 10.1002/mus.24332.

Ataluren treatment of patients with nonsense mutation dystrophinopathy.

Bushby K(1), Finkel R, Wong B, Barohn R, Campbell C, Comi GP, Connolly AM, Day
JW, Flanigan KM, Goemans N, Jones KJ, Mercuri E, Quinlivan R, Renfroe JB,
Russman B, Ryan MM, Tulinius M, Voit T, Moore SA, Lee Sweeney H, Abresch RT,
Coleman KL, Eagle M, Florence J, Gappmaier E, Glanzman AM, Henricson E, Barth J,
Elfring GL, Reha A, Spiegel RJ, O'donnell MW, Peltz SW, Mcdonald CM;
PTC124-GD-007-DMD STUDY GROUP.

Collaborators: Ryan MM, Kornberg AJ, Wray A, Carroll K, Kennedy R, Villano D, de

Valle K, Jones KJ, North KN, Dexter M, Wicks S, Rose K, Goemans N, Buyse GM, van
den Hauwe M, Vrijsen B, Campbell C, Janmohammad A, Scholtes C, Mah JK, Wright
CJ, Chiu A, Walker LM, Sarnat HB, Selby K, King C, Meisner L, Voit T, Doppler V,
De Castro D, Decostre V, Chabrol B, Levy N, Halbert C, Pereon Y, Magot A,
Perrier J, Mahe JY, Perrau AS, Chasserieau R, Schara U, Lutz S, Busse M, Della
Marina A, Bosbach T, Kirschner J, Stanescu A, Pohl A, Rensing-Zimmerman C,
Eisele U, Fetzer I, Vogt S, Bertini E, D'Amico A, Kofler A, Gesu PB, Carlesi A,
Bonetti AM, Gagliardi MG, Santecchia L, Emma F, Bergami G, Mercuri EM, Vasco G,
Bianco F, Mazzone ES, Pane M, De Sanctis R, Comi GP, Magri F, Lucchini V, Corti
SP, Moggio MG, Sciacco M, Govoni A, Bresolin N, Nevo Y, Dor-Wollman T, Bar-Lev
A, Krojanker-Yaffe D, Weisband E, Vilchez JJ, Muelas N, Sevilla T, Smeyers P,
Calle F, González M, de la Osa A, Colomer J, Ortez CI, Nascimento A, Febrer A,
Medina J, Muni R, Tulinius M, Thorarinsdottir B, Darin N, Sterky U, Kroksmark
AK, Berglund L, Sejersen T, Hovmöller M, Trulsson E, Hök A, Kipping P, Bushby
KM, Guglieri M, Straub V, Sàrközy A, Willis T, Eagle M, Mayhew A, McCallum M,
Smith L, Bell G, Muntoni F, Manzur AY, Robb SA, Main M, Ash M, Scoto M, Cirak S,
Quinlivan RC, Smith MR, Pandey R, James S, Emery N, Groves L, Kulshrestha R,
Wong BL, Collins J, McGuire M, McCormick A, Morehart P, Hu S, Brown R, Finkel
RS, Bonnemann CG, Yang ML, Foley AR, Murphy-Kotzer L, Dorsey L, Estilow T,
Glanzman AM, Paisley A, Yum S, Thomas T, Smith K, Gappmaier E, Bromberg MB,
McGerty B, Heidarian LL, Swoboda K, Gappmaier V, Day JW, Karachunski PI,
Margolis M, Naughton C, Buser KK, Dalton J, Matthews KD, Stephan CM, Laubenthal
KS, Darras BT, Kang PB, Riley SO, Quigley J, Butler H, Parsons J, Apkon SD,
Gibbons M, Carey T, Barohn RJ, Dasouki MJ, Anderson HS, Arthur A, Burns JM,
Dimachkie MM, Pasnoor M, Wang YI, Herbelin L, Myles R, Ciafaloni E, Heatwole C,
Eichinger K, Pandya S, Connolly A, Pestronk A, Al-Lozi M, Lopate G, Golumbek P,
Sommerville RB, Wang L, Wojcicka-Mitchell A, Godbey A, Malkus B, Schierbecker J,
Siener C, Lu M, Harms M, Varadachary A, Iyadurai S, Rojas L, Iannacone ST,
Gilbreath H, Khonghatithum C, Merryman R, Nelson L, Andersen M, Greene M, Kern
S, Sproule DM, Kaufmann P, De Vivo D, Battista V, Constantinescu A, Montes J,
Dunaway S, Montgomery M, Marra J, McDonald CM, Han J, Henricson E, Abresch RT,
Joyce N, Goude E, Johnson L, Nicorici A, Cregan M, Renfroe JB, Bougher G,
Keohane T, Russman BS, Sussman MD, Zilke K, del Rosario E, Wechsler SB, Juel VC,
Hobson-Webb L, Smith EC, Mackey J, Case L, Ollendick K.

Author information:
(1)Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne,
United Kingdom.

INTRODUCTION: Dystrophinopathy is a rare, severe muscle disorder, and nonsense

mutations are found in 13% of cases. Ataluren was developed to enable ribosomal
readthrough of premature stop codons in nonsense mutation (nm) genetic
disorders.
METHODS: Randomized, double-blind, placebo-controlled study; males ≥ 5 years
with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10,
10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48
weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week
48.
RESULTS: Ataluren was generally well tolerated. The primary endpoint favored
ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=31.3 meters, post
hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful
differences between ataluren 10, 10, 20 mg/kg, and placebo.
CONCLUSIONS: As the first investigational new drug targeting the underlying
cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this
orphan genetic disorder with high unmet medical need.

Copyright © 2014 Wiley Periodicals, Inc.

DOI: 10.1002/mus.24332
PMCID: PMC4241581
PMID: 25042182 [Indexed for MEDLINE]

2. Muscle Nerve. 2021 Nov;64(5):614-619. doi: 10.1002/mus.27396. Epub 2021 Sep 2.

Evaluating longitudinal therapy effects via the North Star Ambulatory

Assessment.

McDonald CM(1), Wei LJ(2), Flanigan KM(3), Elfring G(4), Trifillis P(4), Muntoni
F(5); ACT DMD Clinical Evaluator Training Group; ACT DMD Study Group.

Author information:
(1)Physical Medicine & Rehabilitation, University of California Davis, Davis,
California, USA.
(2)Harvard University, Boston, Massachusetts, USA.
(3)Nationwide Children's Hospital, Columbus, Ohio, USA.
(4)PTC Therapeutics Inc, South Plainfield, New Jersey, USA.
(5)University College London Great Ormond Street Institute of Child Health and
NIHR Biomedical Research Centre, London, UK.

INTRODUCTION/AIMS: In comparative studies, treatment effects are typically

evaluated at a specific time point. When data are collected periodically, an
alternative, clinically meaningful approach could be used to assess the totality
of treatment effects. We applied a well-developed analytical procedure for
evaluating longitudinal treatment effects using North Star Ambulatory Assessment
(NSAA) data for illustration.
METHODS: The NSAA comprises 17 scorable items/outcomes that measure changes in
motor function. Using NSAA data from the published ataluren phase 3, randomized,
placebo-controlled trial (NCT01826487), cumulative counts of failures to perform
each item (transition from 2/1 [able/impaired] to 0 [unable]) were collected at
specified time points for each patient over 48 wk. Treatment group-wise mean
cumulative item failure count curves were constructed, comparing ataluren versus
placebo and deflazacort versus prednisone/prednisolone among placebo-treated
patients. The steeper the curve, the worse the outcome. A clinically meaningful
summary of the between-group difference was provided for each comparison.
RESULTS: The curve was uniformly steeper for placebo than ataluren after 16 wk
and for prednisone/prednisolone than deflazacort after 8 wk. The two curves in
each comparison continued to diverge thereafter, indicating sustained treatment
benefits over time. Using a unique analytical approach, cumulative failure rates
were reduced, on average, by 27% for ataluren versus placebo (rate ratio, 0.73;
95% confidence interval [CI], 0.55-0.97; p = .027) and 28% for deflazacort
versus prednisone/prednisolone (rate ratio, 0.72; 95% CI, 0.53-0.96; p = .028).
DISCUSSION: Unlike fixed-time analyses, this analytical approach enabled
demonstration of cumulative, longitudinal treatment effects over time using
repeatedly measured NSAA observations.
© 2021 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.

DOI: 10.1002/mus.27396
PMCID: PMC9290940
PMID: 34383312 [Indexed for MEDLINE]

Conflict of interest statement: Craig M. McDonald has acted as a consultant on

clinical trials of DMD for Astellas, Capricor, Catabasis, Edgewise Therapeutics,
Epirium Bio (formerly Cardero Therapeutics), FibroGen, Italfarmaco, Pfizer, PTC
Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics. He has received
research support for clinical trials from Capricor, Catabasis, Italfarmaco,
Pfizer, PTC Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics.
Lee‐Jen Wei has acted as a consultant for Johnson and Johnson, Merck and co.,
Pfizer, PTC Therapeutics and Sarepta Therapeutics. Kevin M. Flanigan has acted
as a consultant for Apic Bio, Audentes Therapeutics, Dynacure, Italfarmaco,
Marathon Pharmaceuticals, PTC Therapeutics, Santhera Pharmaceuticals, Sarepta
Therapeutics, Tivorsan Pharmaceuticals, and 4D Molecular Therapeutics; has been
a clinical trial investigator for Abeona Therapeutics, Akashi Therapeutics
BioMarin and Sarepta Therapeutics; has received grants from Beauhawks Foundation
and CureDuchenne; and has received royalty payment from Audentes Therapeutics.
Gary Elfring and Panayiota Trifillis are employees of PTC Therapeutics.
Francesco Muntoni has received consulting fees from AveXis, Biogen, Dyne
Therapeutics, Capricor, Catabasis, Novartis, Pfizer, PTC Therapeutics, Roche,
Santhera Pharmaceuticals, Sarepta Therapeutics and Wave Therapeutics, and is
supported by the National Institute of Health Research Biomedical Research
Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and
University College London. Medical writing and editorial support were funded by
PTC Therapeutics Ltd.

3. FASEB J. 2014 Apr;28(4):1593-9. doi: 10.1096/fj.13-240044. Epub 2013 Dec 26.

Muscle dysfunction and structural defects of dystrophin-null sapje mutant

zebrafish larvae are rescued by ataluren treatment.

Li M(1), Andersson-Lendahl M, Sejersen T, Arner A.

Author information:
(1)1 Department of Physiology and Pharmacology, Karolinska Institutet, Von
Eulers v 8, SE 171 77 Stockholm, Sweden. anders.arner@ki.se.

Sapje zebrafish carry a mutation in the dystrophin gene, which results in a

premature stop codon, and a severe muscle phenotype. They display several of the
structural characteristics of Duchenne muscular dystrophy (DMD). Ataluren
(PTC124) is proposed to cause readthrough of premature stop codons and has been
introduced as a potential treatment of genetic disorders. Clinical trials in DMD
have shown promise, although with complex dose dependency. We have established
physiology techniques, enabling high resolution of contractile function in
skeletal muscle of zebrafish larvae. We aimed to provide a mechanical analysis
of sapje larval muscle and examine effects of ataluren. Homozygous 5 d
postfertilization (dpf) sapje larvae exhibited structural defects with 50%
decrease in active tension. Ataluren (0.1-1 μM, 3-5 dpf) improved contractile
function (~60% improvement of force at 0.5 μM) and dystrophin expression.
Controls were not affected. Higher doses (5 μM, 35 μM) impaired contractile
function, an effect also observed in controls, suggesting unspecific negative
effects at high concentrations. In summary, Sapje larvae exhibit impaired
contractile performance and provide a relevant DMD model for functional studies.
Ataluren significantly improves skeletal muscle function in the sapje larvae,
most likely reflecting an observed increase in dystrophin expression. The
bell-shaped dose dependence in sapje resembles that previously reported in
clinical DMD studies.

DOI: 10.1096/fj.13-240044
PMID: 24371125 [Indexed for MEDLINE]

4. Eur J Med Chem. 2021 Jan 15;210:112952. doi: 10.1016/j.ejmech.2020.112952. Epub

2020 Oct 22.

Structure-activity relationship (SAR) studies of

N-(3-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (SRI-22819) as NF-ҡB
activators for the treatment of ALS.

Mathew B(1), Ruiz P(2), Dutta S(3), Entrekin JT(4), Zhang S(4), Patel KD(4),
Simmons MS(4), Augelli-Szafran CE(5), Cowell RM(6), Suto MJ(7).

Author information:
(1)Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue
South, Birmingham, AL, 35205, USA. Electronic address:
bmathew@southernresearch.org.
(2)Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue
South, Birmingham, AL, 35205, USA. Electronic address:
pruiz@southernresearch.org.
(3)Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue
South, Birmingham, AL, 35205, USA. Electronic address:
sdutta@southernresearch.org.
(4)Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue
South, Birmingham, AL, 35205, USA.
(5)Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue
South, Birmingham, AL, 35205, USA. Electronic address:
caugelli-szafran@southernresearch.org.
(6)Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue
South, Birmingham, AL, 35205, USA. Electronic address:
rcowell@southernresearch.org.
(7)Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue
South, Birmingham, AL, 35205, USA. Electronic address:
msuto@southernresearch.org.

ALS is a rare type of progressive neurological disease with unknown etiology. It

results in the gradual degeneration and death of motor neurons responsible for
controlling the voluntary muscles. Identification of mutations in the superoxide
dismutase (SOD) 1 gene has been the most significant finding in ALS research.
SOD1 abnormalities have been associated with both familial as well as sporadic
ALS cases. SOD2 is a highly inducible SOD that performs in concurrence with SOD1
to detoxify ROS. Induction of SOD2 can be obtained through activation of NF-ҡBs.
We previously reported that SRI-22819 increases NF-ҡB expression and activation
in vitro, but it has poor ADME properties in general and has no oral
bioavailability. Our initial studies were focused on direct modifications of
SRI-22819. There were active compounds identified but no improvement in
microsomal stability was observed. In this context, we focused on making more
significant structural changes in the core of the molecule. Ataluren, an
oxadiazole compound that promotes read-through and expression of dystrophin in
patients with Duchenne muscular dystrophy, bears some structural similarity to
SRI-22819. Thus, we synthesized a series of SRI-22819 and Ataluren (PTC124)
hybrid compounds. Several compounds from this series exhibited improved
activity, microsomal stability and lower calculated polar surface area (PSA).
This manuscript describes the synthesis and biological evaluation of SRI-22819
analogs and its hybrid combination with Ataluren.
Copyright © 2020 Elsevier Masson SAS. All rights reserved.

DOI: 10.1016/j.ejmech.2020.112952
PMID: 33139114 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors

declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this
paper.

5. Muscle Nerve. 2013 Sep;48(3):343-56. doi: 10.1002/mus.23902. Epub 2013 Jun 26.

The 6-minute walk test and other endpoints in Duchenne muscular dystrophy:
longitudinal natural history observations over 48 weeks from a multicenter
study.

McDonald CM(1), Henricson EK, Abresch RT, Florence JM, Eagle M, Gappmaier E,
Glanzman AM; PTC124-GD-007-DMD Study Group; Spiegel R, Barth J, Elfring G, Reha
A, Peltz S.

Collaborators: Ryan M, Jones K, Goemans N, Campbell C, Mah J, Selby K, Voit T,

Chabrol B, Pereon Y, Schara U, Kirschner J, Bertini E, Mercuri E, Comi G, Nevo
Y, Vilchez J, Colomer J, Children S, Tulinius M, Sejersen T, Bushby K, Muntoni
F, Quinlivan RC, Wong B, Finkel RS, Sampson JB, Flanigan KM, Butterfield R, Day
JW, Mathews K, Darras BT, Apkon SD, Parsons J, Barohn R, Connolly A, Iannaccone
S, Sproule DM, Kaufman P, Han JJ, Joyce NC, Renfroe J, Russman BS,
Burns-Wechsler S, Moore SA, Sweeney HL, Coleman K.

Author information:
(1)Department of Physical Medicine and Rehabilitation, University of California
Davis School of Medicine, Davis, California, 95817, USA.

Comment in
Muscle Nerve. 2013 Sep;48(3):315-7. doi: 10.1002/mus.23984.

INTRODUCTION: Duchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense

mutations were followed for 48 weeks in a multicenter, randomized, double-blind,
placebo-controlled trial of ataluren. Placebo arm data (N = 57) provided insight
into the natural history of the 6-minute walk test (6MWT) and other endpoints.
METHODS: Evaluations performed every 6 weeks included the 6-minute walk distance
(6MWD), timed function tests (TFTs), and quantitative strength using hand-held
myometry.
RESULTS: Baseline age (≥7 years), 6MWD, and selected TFT performance are strong
predictors of decline in ambulation (Δ6MWD) and time to 10% worsening in 6MWD. A
baseline 6MWD of <350 meters was associated with greater functional decline, and
loss of ambulation was only seen in those with baseline 6MWD <325 meters. Only 1
of 42 (2.3%) subjects able to stand from supine lost ambulation.
CONCLUSION: Findings confirm the clinical meaningfulness of the 6MWD as the most
accepted primary clinical endpoint in ambulatory DMD trials.

Copyright © 2013 Wiley Periodicals, Inc.

DOI: 10.1002/mus.23902
PMCID: PMC3824082
PMID: 23681930 [Indexed for MEDLINE]
6. Acta Myol. 2018 Dec 1;37(4):272-274. eCollection 2018 Dec.

Therapeutic approach with Ataluren in Duchenne symptomatic carriers with

nonsense mutations in dystrophin gene. Results of a 9-month follow-up in a case
report.

D'Ambrosio P(1), Orsini C(1), Nigro V(2), Politano L(1).

Author information:
(1)Cardiomyology and Medical Genetics, Department of Experimental Medicine,
University of Campania "Luigi Vanvitelli", Naples, Italy.
(2)Laboratory of Medical Genetics, Department of Precision's Medicine,
University of Campania "Luigi Vanvitelli", Naples, Italy.

Duchenne muscular Dystrophy (DMD) is a X-linked degenerative disorder affecting

skeletal muscles and myocardium caused by mutations in the dystrophin gene,
mainly deletions and duplications. Point-mutations account for 13% and stop
codon mutations are even more unfrequent. A drug treatment for patients with DMD
caused by stop codon gene mutations and still ambulant, has become recently
available, based on the clear demonstration of its efficacy in slowing the
course of the disease. The drug is able to read through the stop codon;
furthermore it has the advantage of an oral administration and a better
patient's compliance. We report a case of a still ambulant 27 year-old DMD
symptomatic carrier with a stop-codon mutation in exon 53 (c.7792C > T;
p.Gln2598Stop), who started the treatment with Ataluren at a dosage of 2,250
mg/die, reporting a prompt subjective improvement in muscle strength.
Unfortunately two months after, the patient discontinued taking the drug for a
traumatic femur fracture requiring surgical repair and prolonged rehabilitation.
With the resumption of the drug intake in February 2018, the patient reported
almost immediately an improvement in motor skills, including the possibility of
recovering walking, first with support and then unsupported. These results seem
even more encouraging, as Duchenne patients hardly recover the ability to walk
following a fracture at this age and extend the possibility to treat with
ataluren also the symptomatic Duchenne carriers who have nonsense dystrophin
gene mutations. Furthermore the case here reported supports the concept that
symptomatic DMD female carriers must enjoy the same therapeutic opportunities
offered to males.

PMCID: PMC6416700
PMID: 30944907 [Indexed for MEDLINE]

7. Biomolecules. 2023 Jan 27;13(2):242. doi: 10.3390/biom13020242.

A High-Throughput Assay for In Vitro Determination of Release Factor-Dependent

Peptide Release from a Pretermination Complex by Fluorescence
Anisotropy-Application to Nonsense Suppressor Screening and Mechanistic Studies.

Ghelfi MD(1), Bhat SY(1), Li H(1), Cooperman BS(1).

Author information:
(1)Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104,
USA.

Premature termination codons (PTCs) account for ~12% of all human disease
mutations. Translation readthrough-inducing drugs (TRIDs) are prominent among
the several therapeutic approaches being used to overcome PTCs. Ataluren is the
only TRID that has been approved for treating patients suffering from a PTC
disease, Duchenne muscular dystrophy, but it gives variable readthrough results
in cells isolated from patients suffering from other PTC diseases. We recently
elucidated ataluren's mechanism of action as a competitive inhibitor of release
factor complex (RFC) catalysis of premature termination and identified
ataluren's binding sites on the ribosome responsible for such an inhibition.
These results suggest the possibility of discovering new TRIDs, which would
retain ataluren's low toxicity while displaying greater potency and generality
in stimulating readthrough via the inhibition of termination. Here we present a
detailed description of a new in vitro plate reader assay that we are using both
to screen small compound libraries for the inhibition of RFC-dependent peptide
release and to better understand the influence of termination codon identity and
sequence context on RFC activity.

DOI: 10.3390/biom13020242
PMCID: PMC9953321
PMID: 36830611 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest.

8. J Hum Genet. 2022 Nov;67(11):661-668. doi: 10.1038/s10038-022-01072-7. Epub 2022

Aug 9.

Functional restoration of mouse Nf1 nonsense alleles in differentiated cultured

neurons.

Wu C(1), Iyer S(2), Wolfe SA(2)(3), Jacobson A(4)(5).

Author information:
(1)Department of Microbiology and Physiological Systems, UMass Chan Medical
School, 368 Plantation Street, Worcester, MA, 01605, USA.
(2)Department of Molecular Cell and Cancer Biology, UMass Chan Medical School,
368 Plantation Street, Worcester, MA, 01605, USA.
(3)Li Weibo Institute for Rare Disease Research, UMass Chan Medical School, 368
Plantation Street, Worcester, MA, 01605, USA.
(4)Department of Microbiology and Physiological Systems, UMass Chan Medical
School, 368 Plantation Street, Worcester, MA, 01605, USA.
allan.jacobson@umassmed.edu.
(5)Li Weibo Institute for Rare Disease Research, UMass Chan Medical School, 368
Plantation Street, Worcester, MA, 01605, USA. allan.jacobson@umassmed.edu.

Neurofibromatosis type 1 (NF1), one of the most common autosomal dominant

genetic disorders, is caused by mutations in the NF1 gene. NF1 patients have a
wide variety of manifestations with a subset at high risk for the development of
tumors in the central nervous system (CNS). Nonsense mutations that result in
the synthesis of truncated NF1 protein (neurofibromin) are strongly associated
with CNS tumors. Therapeutic nonsense suppression with small molecule drugs is a
potentially powerful approach to restore the expression of genes harboring
nonsense mutations. Ataluren is one such drug that has been shown to restore
full-length functional protein in several models of nonsense mutation diseases,
as well as in patients with nonsense mutation Duchenne muscular dystrophy. To
test ataluren's potential applicability to NF1 nonsense mutations associated
with CNS tumors, we generated a homozygous Nf1R683X/R683X-3X-FLAG mouse
embryonic stem (mES) cell line which recapitulates an NF1 patient nonsense
mutation (c.2041 C > T; p.Arg681X). We differentiated Nf1R683X/R683X-3X-FLAG mES
cells into cortical neurons in vitro, treated the cells with ataluren, and
demonstrated that ataluren can promote readthrough of the nonsense mutation at
codon 683 of Nf1 mRNA in neural cells. The resulting full-length protein is able
to reduce the cellular level of hyperactive phosphorylated ERK (pERK), a RAS
effector normally suppressed by the NF1 protein.
© 2022. The Author(s), under exclusive licence to The Japan Society of Human
Genetics.

DOI: 10.1038/s10038-022-01072-7
PMID: 35945271 [Indexed for MEDLINE]