Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia.


Objective:Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose-ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (NCT02255435). Methods:Sixty-nine Friedreich ataxia patients were randomized 3:1 to either omaveloxolone or placebo administered once daily for 12 weeks. Patients were randomized in cohorts of eight patients, at dose levels of 2.5-300 mg/day. Results:Omaveloxolone was well tolerated, and adverse events were generally mild. Optimal pharmacodynamic changes (noted by changes in ferritin and GGT) were observed at doses of 80 and 160 mg/day. No significant changes were observed in the primary outcome, peak work load in maximal exercise testing (0.9 ± 2.9 W, placebo corrected). At the 160 mg/day dose, omaveloxolone improved the secondary outcome of the mFARS by 3.8 points versus baseline (P = 0.0001) and by 2.3 points versus placebo (P = 0.06). Omaveloxolone produced greater improvements in mFARS in patients that did not have musculoskeletal foot deformity (pes cavus). In patients without this foot deformity, omaveloxolone improved mFARS by 6.0 points from baseline (P < 0.0001) and by 4.4 points versus placebo (P = 0.01) at the 160 mg/day. Interpretation:Treatment of Friedreich ataxia patients with omaveloxolone at the optimal dose level of 160 mg/day appears to improve neurological function. Therefore, omaveloxolone treatment is being examined in greater detail at 150 mg/day for Friedreich ataxia.


Ann Clin Transl Neurol


Lynch DR,Farmer J,Hauser L,Blair IA,Wang QQ,Mesaros C,Snyder N,Boesch S,Chin M,Delatycki MB,Giunti P,Goldsberry A,Hoyle C,McBride MG,Nachbauer W,O'Grady M,Perlman S,Subramony SH,Wilmot GR,Zesiewicz T,Meyer C




Has Abstract


2018-11-10 00:00:00












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    authors: Fang P,Yu Y,Yao S,Chen S,Zhu M,Chen Y,Zou K,Wang L,Wang H,Xin L,Hong T,Hong D

    更新日期:2020-04-01 00:00:00

  • Rescue levodopa-carbidopa intestinal gel (LCIG) therapy in Parkinson's disease patients with suboptimal response to deep brain stimulation.

    abstract:OBJECTIVE:To evaluate the effectiveness of levodopa-carbidopa intestinal gel (LCIG) as an add-on rescue therapy following deep brain stimulation (DBS) for treatment of motor fluctuations. BACKGROUND:Both DBS and LCIG are FDA-approved therapies for treatment of motor fluctuations in advanced PD. Few studies have examin...

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    authors: Elkouzi A,Ramirez-Zamora A,Zeilman P,Barabas M,Eisinger RS,Malaty IA,Okun MS,Almeida L

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  • Treatment of natalizumab-associated PML with filgrastim.

    abstract:Objective:There is no consensus on the treatment of progressive multifocal leukoencephalopathy (PML) occurring in multiple sclerosis (MS) patients treated with natalizumab (Nz). We report novel immune activating treatment with filgrastim of Nz-associated PML in MS patients treated at Rush University Medical Center. Me...

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    authors: Stefoski D,Balabanov R,Waheed R,Ko M,Koralnik IJ,Sierra Morales F

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  • Targeted gene panel use in 2249 neuromuscular patients: the Australasian referral center experience.

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    pub_type: 杂志文章


    authors: Beecroft SJ,Yau KS,Allcock RJN,Mina K,Gooding R,Faiz F,Atkinson VJ,Wise C,Sivadorai P,Trajanoski D,Kresoje N,Ong R,Duff RM,Cabrera-Serrano M,Nowak KJ,Pachter N,Ravenscroft G,Lamont PJ,Davis MR,Laing NG

    更新日期:2020-03-01 00:00:00

  • A single-center SCN8A-related epilepsy cohort: clinical, genetic, and physiologic characterization.

    abstract:OBJECTIVE:Pathogenic variants in SCN8A, encoding the voltage-gated sodium (Na+) channel α subunit Nav1.6, is a known cause of epilepsy. Here, we describe clinical and genetic features of all patients with SCN8A epilepsy evaluated at a single-tertiary care center, with biophysical data on identified Nav1.6 variants and ...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: Zaman T,Abou Tayoun A,Goldberg EM

    更新日期:2019-08-01 00:00:00

  • An image-based model of brain volume biomarker changes in Huntington's disease.

    abstract:Objective:Determining the sequence in which Huntington's disease biomarkers become abnormal can provide important insights into the disease progression and a quantitative tool for patient stratification. Here, we construct and present a uniquely fine-grained model of temporal progression of Huntington's disease from pr...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: Wijeratne PA,Young AL,Oxtoby NP,Marinescu RV,Firth NC,Johnson EB,Mohan A,Sampaio C,Scahill RI,Tabrizi SJ,Alexander DC

    更新日期:2018-04-02 00:00:00

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    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: Varhaug KN,Nido GS,de Coo I,Isohanni P,Suomalainen A,Tzoulis C,Knappskog P,Bindoff LA

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  • Expression of IL-33 and its epigenetic regulation in Multiple Sclerosis.

    abstract::We examined the expression of IL-33 as an indicator of an innate immune response in relapsing remitting MS (RRMS) and controls. Based on our previous studies we proposed a link between the expression of IL-33 and IL-33 regulated genes to histone deacetylase (HDAC) activity and in particular HDAC3, an enzyme that plays...

    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: Zhang F,Tossberg JT,Spurlock CF,Yao SY,Aune TM,Sriram S

    更新日期:2014-05-01 00:00:00

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    abstract:OBJECTIVE:To examine how urate concentrations are related to the risk of having possible REM sleep behavior disorder (pRBD) in a community-based cohort. METHODS:The study included 12,923 Chinese adults of the Kailuan Study, free of Parkinson disease (PD) and dementia. Plasma urate concentrations were measured in 2006,...

    journal_title:Annals of clinical and translational neurology

    pub_type: 临床试验,杂志文章


    authors: Shen Y,Li J,Schwarzschild M,Pavlova M,He S,Ascherio A,Wu S,Cui L,Gao X

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  • White matter predicts functional connectivity in premanifest Huntington's disease.

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    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: McColgan P,Gregory S,Razi A,Seunarine KK,Gargouri F,Durr A,Roos RA,Leavitt BR,Scahill RI,Clark CA,Tabrizi SJ,Rees G,Track On‐HD Investigators.,Coleman A,Decolongon J,Fan M,Petkau T,Jauffret C,Justo D,Lehericy S,Ni

    更新日期:2017-01-16 00:00:00

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    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: Antelmi E,Pizza F,Donadio V,Filardi M,Sosero YL,Incensi A,Vandi S,Moresco M,Ferri R,Marelli S,Ferini-Strambi L,Liguori R,Plazzi G

    更新日期:2019-09-01 00:00:00

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    authors: Venuto CS,Yang L,Javidnia M,Oakes D,James Surmeier D,Simuni T

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    authors: Abner EL,Jicha GA,Shaw LM,Trojanowski JQ,Goetzl EJ

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    authors: Hawkins NA,Anderson LL,Gertler TS,Laux L,George AL Jr,Kearney JA

    更新日期:2017-04-26 00:00:00

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    authors: Ishihara M,Araya N,Sato T,Saichi N,Fujii R,Yamano Y,Ueda K

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    journal_title:Annals of clinical and translational neurology

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    authors: Wood AG,Chen J,Barton S,Nadebaum C,Anderson VA,Catroppa C,Reutens DC,O'Brien TJ,Vajda F

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    journal_title:Annals of clinical and translational neurology

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    journal_title:Annals of clinical and translational neurology

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: Gonorazky H,Liang M,Cummings B,Lek M,Micallef J,Hawkins C,Basran R,Cohn R,Wilson MD,MacArthur D,Marshall CR,Ray PN,Dowling JJ

    更新日期:2015-12-08 00:00:00

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    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: Waung MW,Akerman S,Wakefield M,Keywood C,Goadsby PJ

    更新日期:2016-07-01 00:00:00

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    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


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    更新日期:2017-09-08 00:00:00

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    journal_title:Annals of clinical and translational neurology

    pub_type: 杂志文章


    authors: Anthony DC,Dickens AM,Seneca N,Couch Y,Campbell S,Checa B,Kersemans V,Warren EA,Tredwell M,Sibson NR,Gouverneur V,Leppert D

    更新日期:2014-09-01 00:00:00