Recent Changes

Saturday, February 17

  1. page Accelerating - Open Notebook Science edited ... Dr. Bradley's USEFULCHEM open notebook science Wikispace Dr. Bradley ONS 2012 presentation at…
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    Dr. Bradley's USEFULCHEM open notebook science Wikispace
    Dr. Bradley ONS 2012 presentation at Georgia Tech
    INACTIVE LINK - Dr. Bradley's Drexel University lab website
    Miscellaneous news and articles:
    Power to the People: Participant Ownership of Clinical Trial Data: http://stm.sciencemag.org/content/3/69/69cm3.full
    (view changes)
    11:32 am
  2. page Accelerating - Open Notebook Science edited ... Links to Dr. Bradley's work: Interview with Dr. Bradley on the "Impact of Open Notebook …
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    Links to Dr. Bradley's work:
    Interview with Dr. Bradley on the "Impact of Open Notebook Science"
    Dr. Bradley's Drexel University lab website
    Dr. Bradley's USEFULCHEM open notebook science Wikispace
    Dr. Bradley ONS 2012 presentation at Georgia Tech
    INACTIVE LINK - Dr. Bradley's Drexel University lab website
    Miscellaneous news and articles:
    Power to the People: Participant Ownership of Clinical Trial Data: http://stm.sciencemag.org/content/3/69/69cm3.full
    (view changes)
    10:59 am

Monday, November 20

  1. 4:18 am
  2. user_add Tishco Tishco joined CHMINFO
    4:17 am

Tuesday, September 13

  1. msg test post message posted test post testing posts
    test post
    testing posts
    11:16 am

Thursday, June 16

  1. page Basic Research, Data, Registries edited ... Translation bypass of NM nutations in Zebrafish rep1 pax2.1 lamb1 2008-Moosajee-Hum Mol Genet-…
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    Translation bypass of NM nutations in Zebrafish rep1 pax2.1 lamb1 2008-Moosajee-Hum Mol Genet-3987-4000.pdf {Translation bypass of NM nutations in Zebrafish rep1 pax2.1 lamb1 2008-Moosajee-Hum Mol Genet-3987-4000.pdf}
    Human CHM Cells:
    Coriell/NIGMS CHM Human Cell Biobank - iPS lines from GM25383 & 25393 to be added July 2016: https://catalog.coriell.org/0/Sections/BrowseCatalog/DiseaseDetail.aspx?PgId=403&omim=CHO30310&coll=
    2013 AAV-Mediated Gene Therapy for CHM in vitro models-Vasireddy,Bennett,Maguire,Black,Chung-PLOS-5-7-13.pdf {2013 AAV-Mediated Gene Therapy for CHM in vitro models-Vasireddy,Bennett,Maguire,Black,Chung-PLOS-5-7-13.pdf}
    2003 Bennett CHM in-vitro Vision Research 2003.pdf {2003 Bennett CHM in-vitro Vision Research 2003.pdf} - NOT PUBLISHED IN PLOS
    CHM-AAV5-_Hamel_Kalatzis_etal-Molecular Therapy-Apr 2014.pdf {CHM-AAV5-_Hamel_Kalatzis_etal-Molecular Therapy-Apr 2014.pdf} - NOT PUBLISHED IN PLOS - The characterization of genomic DNA from the fibroblasts of patient CHM1 reveals duplication and deletion of sequences at the intron 7-exon 8 junction that lead to loss of the intron 7 acceptor splice site and thus deletion of exon 8 - First creation of human CHM iPS and RPE models.
    BiobankingBiorepository Information:
    A biorepository for ophthalmic surgical specimens - Skeie JM, Tsang SH, Zande RV, Fickbohm MM, Shah SS, Vallone JG, Mahajan VB. Proteomics Clin Appl. 2013 Sep 24. doi: 10.1002/prca.201300043 - Department of Ophthalmology and Visual Sciences; Omics Laboratory, University of Iowa, Iowa City, IA: http://www.ncbi.nlm.nih.gov/pubmed/24115637
    CHM Human Trials and Pre-Clinical Research:
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    11:50 am

Tuesday, June 14

  1. page Accelerating - Open Notebook Science edited ... From Wikipedia, the free encyclopedia: Open Notebook Science is the practice of making the en…
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    From Wikipedia, the free encyclopedia:
    Open Notebook Science is the practice of making the entire primary record of a research project publicly available online as it is recorded. This involves placing the personal, or laboratory, notebook of the researcher online along with all raw and processed data, and any associated material, as this material is generated. The approach may be summed up by the slogan 'no insider information'. It is the logical extreme of transparent approaches to research and explicitly includes the making available of failed, less significant, and otherwise unpublished experiments; so called 'Dark Data'.[1] The practice of Open Notebook Science, although not the norm in the academic community, has gained significant recent attention in the research,[2][3] general,[1][4] and peer-reviewed[5] media as part of a general trend towards more open approaches in research practice and publishing. Open Notebook Science can therefore be described as part of a wider open Science movement that includes the advocacy and adoption of open access publication, open data,crowdsourcing data, and citizen science. It is inspired in part by the success of open-source software[6] and draws on many of its ideas. Click for more.
    Crowdsourcing: an overview and applications to ophthalmology
    http://www.ncbi.nlm.nih.gov/pubmed/26761188

    Jean-Claude Bradley is an organic chemist at Drexel University in Philadelphia. As with most scientists, Bradley used to be very secretive. He kept his research under wraps until publication and frequently applied for patents on his work in nanotechnology and gene therapy: Dr. Bradley has now become a practicioner of and outspoken proponent for open notebook science.
    Links to Dr. Bradley's work:
    (view changes)
    11:08 am

Monday, December 28

  1. 10:39 am
  2. user_add Tracigoc Tracigoc joined CHMINFO
    10:37 am

Monday, November 23

  1. page Outcome Measure Notes edited CHM Therapy Outcome Measure Notes Following is DRAFT rev 11-23-2015 Opening notes: Loss of visua…
    CHM Therapy Outcome Measure Notes Following is DRAFT rev 11-23-2015
    Opening notes:
    Loss of visual field and sensitivity corresponds with loss of structure in CHM, - preserve structure = stop or slow sight loss: OCT (4+plane), volumetric OCT topography, fundus photography, autofluorescence, OCT angiography, AOSLO
    Visual field: Goldmann, Humphrey, Octopus next generation microperimetry
    Light sensitivity: next generation Microperimetry, full field scotopic/photopic sensitivity
    Color sensitivity: Farnsworth Munsell 100 or 15 hue color sensitivity test (manual and computerized versions)
    Functional tests for paper reading and or ambulation at variable light and light to dark and dark to light adaptation time
    Visual acuity as primarily a safety measure
    Relevant endpoints (additional references available):
    Visual field (microperimetry, Goldmann, Humphrey), retinal sensitivity and full field scotopic threshold: __http://www.ncbi.nlm.nih.gov/pubmed/24093180__ Current MP is performed on two axes, MP measures on 4 or more axes would be more informative.
    SD-OCT changes in retinal structure correlated to visual fied: __http://www.ncbi.nlm.nih.gov/pubmed/23828615__ - Current OCT is performed on two axes, OCT measures on 4 or more axes would be more informative.
    Changes in fundus appearance and autofluorescence correlated to visual field: __http://www.ncbi.nlm.nih.gov/pubmed/23299470__
    Ellipsoid Zone (EZ) Area publications regarding correlation of retinal structure to visual field:
    Dr. Birch - Ellipsoid Zone OCT aka EZ Area validation being sought from FDA
    __A Comparison of Methods for Tracking Progression in X-Linked Retinitis Pigmentosa Using Frequency Domain OCT.__ Ramachandran R, Zhou L, Locke KG, Birch DG, Hood DC. Transl Vis Sci Technol. 2013 Nov;2(7):5. Epub 2013 Nov 11. PMID:24349883
    __Spectral-domain optical coherence tomography measures of outer segment layer progression in patients with X-linked retinitis pigmentosa.__ Birch DG, Locke KG, Wen Y, Locke KI, Hoffman DR, Hood DC.JAMA Ophthalmol. 2013 Sep;131(9):1143-50. doi: 10.1001/jamaophthalmol.2013.4160. PMID:23828615.
    __Transition zones between healthy and diseased retina in choroideremia (CHM) and Stargardt disease (STGD) as compared to retinitis pigmentosa (RP).__ Lazow MA, Hood DC, Ramachandran R, Burke TR, Wang YZ, Greenstein VC, Birch DG. Invest Ophthalmol Vis Sci. 2011 Dec 20;52(13):9581-90. doi: 0.1167/iovs.11-8554. PMID:22076985
    __Method for deriving visual field boundaries from OCT scans of patients with retinitis pigmentosa.__ Hood DC, Ramachandran R, Holopigian K, Lazow M, Birch DG, Greenstein VC. Biomed Opt Express. 2011 Apr 5;2(5):1106-14. doi: 10.1364/BOE.2.001106. PMID: 21559123
    Possible additional endpoints:
    IreST reading test - 9 point arial? in 75-125 (not variable, fixed within this range) ft candle lighting-__http://precision-vision.com/all-products/near-vision-reading-charts/reading-cards/irest-internationalreadingspeedtexts.html#.VjkRc7erSUk__
    Peli Robson contrast sensitivity chart at one meter (used a 1m stick for positioning) tested R eye on chart 1 of 2 and L eye on chart 2 of 2 in 75-125 (not variable, fixed within this range) ft candle lighting -__http://precision-vision.com/all-products/contrast-eye-charts/mixed-threshold-contrast-charts/threshold-contrast/pelli-robsonsloanlettercontrastchart.html#.VjkShrerSUk__
    Farnsworth-Munsell 100-hue color sensitivity (to be further evaluated): __http://www.ncbi.nlm.nih.gov/pubmed/24097078__
    Farnsworth Munsell 100 Hue Test - Color recognition - standard illuminant C lighting - Oxford poster at ARVO 2014: __http://abstracts.iovs.org//cgi/content/abstract/55/5/6242?sid=b11ec183-2215-4939-ba5d-9d0feaa10a02__
    ETDRS visual acuity as a safety measure (if required): __http://www.ncbi.nlm.nih.gov/pubmed/20126505__
    See light to dark / dark to light and reading ability notes on next page
    Standard diagnostics and measures:
    ETDRS VA (Reported in Lancet)
    OCT changes in retinal structure (Reported in Lancet)
    Microperimetry (Reported in Lancet)
    Dark adapted retinal sensitivity (Reported in Lancet)
    Fundus photography (Reported in Lancet)
    Autofluorescence (Reported in Lancet)
    Contrast sensitivity
    Full field scotopic/photopic threshold
    Goldmann VF
    Humphrey VF
    Esterman VF
    Octopus VF?
    ERG
    Other notes:
    Adaptive optics not widely available: __http://www.ncbi.nlm.nih.gov/pubmed/25190651__
    Mobility course is primary outcome measure for the Phase III LCA2/RPE65 gene therapy trial in the US based on the clinicaltrials.gov listing. It will be challenging to use such an obstacle course for CHM due to the fact that sight loss precedes cell loss in LCA2 and sight loss is closely correlated to cell loss in CHM. Dramatic improvements in field of vision are not expected in CHM gene therapy trials as have been seen in the LCA2 trials, particularly in younger patients.
    No published data for CHM:
    Functional MRI - visual cortex (LCA2)
    Pupillary light reflex (LCA2)
    Additional considerations and options:
    Patient selection - symmetrical and rapid disease progression
    Biomarkers - non-molecular for now until in vivo protein activity detection possible
    Reading ability/speed - reduction in or loss of the ability to read is the most common reason for disability - __http://www.ncbi.nlm.nih.gov/pubmed/16395143__
    Possible variation on reading test:
    Reading test incorporating variable light levels and printed text:
    Placement of a printed page with standardized font in black on standardized brightness level white page at standardized distance for reading - IreST standard text
    Dark or light adapt?
    Add controlled light with variable intensity
    Record reading speed in 1? minute incremental blocks while increasing light level by 1 lux steps each 1? minute starting at zero and increasing until reading speed plateaus
    Add reverse high to low light intensity test?
    Light to dark and dark to light adaptation time for reading, navigation, etc.
    Incorporate varying light levels into paper based VA, VF, contrast and color sensitivity or other measures where a pre and post treatment difference can be measured.
    NEI Visual Function Questionnaire 25 or similar assessment: __https://catalog.nei.nih.gov/p-300-visual-function-questionnaire-25.aspx__
    OCT & HEP - Device to correlate VF to structure via OCT & VF:
    __http://www.heidelbergengineering.com/international/products/hep/spectralis-hep/__
    BPEI photosensitivity tester - ARVO 2014 poster:
    __http://www.arvo.org/webs/am2015/abstract/423.pdf__
    Relevant Trials:RW 6-10-2015
    NightstaRx, Inc. (__www.nightstarx.com__) in the United Kingdom is sponsoring gene therapy clinical trials
    Phase I/II clinical trial for CHM Oct 2011: __http://www.clinicaltrials.gov/ct2/show/NCT01461213__
    12 patients non-randomized - 6 low dose 1x10(10), 6 high dose 1x10(11)
    6 month followup for primary outcome measures
    24 month followup for secondary outcome measures
    Publication of initial results: __http://www.ncbi.nlm.nih.gov/pubmed/24439297__
    Primary Outcome Measures:
    Visual acuity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Best corrected visual acuity, following cataract surgery if indicated
    Secondary Outcome Measures:
    Microperimetry, OCT and fundus autofluorescence [Time Frame: 24 months ] [ Designated as safety issue: No]
    Structure function correlations at the margins of the retinal degeneration
    Phase II clinical trial for CHM Mar 2015: __https://clinicaltrials.gov/ct2/show/NCT02407678__
    30 patients non-randomized
    Primary outcome measures
    Change from baseline in best corrected visual acuity in treated eye, compared to untreated control eye [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Secondary outcome measures
    Change from baseline in autofluorescence evaluation in treated eye, compared to untreated control eye [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Change from baseline in central visual field using microperimetry readings in treated eye, compared to untreated control eye [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Spark Therapeutics (__www.sparktx.com__) is sponsoring a Phase 1-2 study of AAV2-hCHM gene therapy for REP1/CHM: __https://clinicaltrials.gov/ct2/show/NCT02341807__
    10 patients - 5 low dose 5x10(10), 5 high dose 1x10(11)
    Primary Outcome Measures:
    -Safety and tolerability (assessed by physical exam, vital signs, laboratory changes over time, and adverse events) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    -Safety and tolerability of a single dose of AAV2-hCHM will be assessed by physical exam, vital signs, laboratory changes over time, and adverse events.
    Ian MacDonald - University of Alberta is sponsoring a Phase I safety study utilizing the NightstaRx AAV2/CHM vector: __http://clinicaltrials.gov/ct2/show/NCT02077361__
    6 subjects non-randomized - 1x10(11)
    Primary Outcome Measures:
    Number of patients with ocular and systemic adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ] This is assessed by standard ocular examinations and vector dissemination and inflammation assays.
    Secondary Outcome Measures:
    Changes in visual field [ Time Frame: Baseline and up to 2 years following vector delivery ] [ Designated as safety issue: Yes ] - This is assessed by Goldmann perimetry and microperimetry; measurements before and after vector delivery are compared.
    Changes in visual function [ Time Frame: Baseline and 2 years following vector delivery ] [ Designated as safety issue: Yes ] - This is assessed by multifocal electrophysiology, full field scotopic threshold, spectral domain optical coherence tomography, fundus photography and fundus autofluorescence; measurements before and after vector delivery are compared.
    Byron Lam - University of Miami BPEI is sponsoring a Phase I safety study utilizing the NightstaRx AAV2-REP1 (10e11 vg) vector: __https://clinicaltrials.gov/ct2/show/NCT02553135__
    6 subjects non-randomized
    Primary Outcome Measures:
    Change in best corrected visual acuity from baseline [Time Frame: 24 Months] [Designated as safety issue: No] ETDRS visual acuity chart
    Secondary Outcome Measures:
    Change in retinal macular autofluorescence from baseline [Time Frame: 24 months ] [ Designated as safety issue: No ] Macular autofluorescence
    Changes in microperimetry from baseline [ Time Frame: 24 months ] [ Designated as safety issue: No ] Macular microperimetry
    Number of participants who experience an adverse event [ Time Frame: 24 months ] [ Designated as safety issue: Yes ] Adverse events during treatment and follow-up period
    Notes:
    Expecting similar six patient NightstaRx vector study at Tubingen Germany to start ~late 2015
    The investigator sponsored phase I studies are starting at high dose 1x10(11)
    Spark Therapeutics (__www.sparktx.com__) is sponsoring a Phase III study of AAV2-hRPE65v2 gene therapy for RPE65/LCA2: __http://clinicaltrials.gov/ct2/show/NCT00999609__
    24 patients - 16 in treatment group and 8 in control group
    Primary Outcome Measures:
    Mobility testing [ Time Frame: One year ] [ Designated as safety issue: No ]
    Secondary Outcome Measures:
    Additional visual/retinal function tests [ Time Frame: One year ] [ Designated as safety issue: No ]
    Ophthalmic exams, physical exams, immunology studies, clinical labs, & adverse event recording [Time Frame: Two years] [Designated as safety issue: Yes]
    Applied Genetic Technologies Corp. is sponsoring a Phase I/II study of rAAV2-CB-hRPE65 gene therapy for RPE65/LCA2: __http://clinicaltrials.gov/ct2/show/NCT00749957__
    12 patients non-randomized
    12 month followup for primary outcome measures
    12 month followup for secondary outcome measures
    Sanofi is sponsoring a Phase I/II study of EAIV/ABCA4 gene therapy for Stargardt’s disease:
    __http://clinicaltrials.gov/ct2/show/NCT01367444__
    28 patients non-randomized
    48 weeks followup for primary outcome measures
    48 weeks followup for secondary outcome measures
    Sanofi additional clinicaltrials.gov listing for long term followup:__http://clinicaltrials.gov/ct2/show/NCT01736592__
    The Foundation Fighting Blindness Clinical Research Institute (__http://www.nnri.info/__) is sponsoring a Phase II efficacy study of Valproic Acid (FDA approved for other indications) for autosomal dominant Retinitis Pigmentosa: __http://clinicaltrials.gov/ct2/show/NCT01233609__
    90 patients randomized
    52 week followup for primary outcome measures
    15 month followup maximum for secondary outcome measures
    Microperimetry Devices
    __http://www.optos.com/en-US/Products/Retinal-imaging-products/OCT-imaging/Microperimetry/__
    Field 29.8 Max 20dB
    __http://www.centervue.com/product.php?id=639__
    Field 36 Max 36dB
    __http://www.nidektechnologies.it/ProductsMP1All.htm__
    Field 22.58 Max 20dB
    Note: Nidek plans to introduce the MP-3 with 34dB capability in mid 2015 in EU and mid 2016 in US but it will not have scotopic capability
    Publications:
    Assessment of Central Retinal Sensitivity Employing Two Types of Microperimetry Devices - Liu etal TVST - 2014: __http://tvstjournal.org/doi/pdf/10.1167/tvst.3.5.3__
    Main testing parameters of the OCT/SLO and the MP-1
    Parameter OCT/SLO / MP-1
    Field of review 298 / 22.58
    Background illumination/color 10 cd/m2/white / 1.27 cd/m2/white
    Maximum differential Luminance 125 cd/m2 / 127 cd/m2
    Stimulus size/color Goldmann II/white / Goldmann III/white
    Stimulus duration/intervals 200/1500 ms / 200/1500 ms
    Attenuation scale 0–20 dB / 0–20 dB
    Fixation target Red cross/28 diameter / Red cross/28 diameter
    Test grid Polar-3 (28 points) / Polar-3 (28 points)
    Threshold strategy 4-2 / 4-2

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    2:09 pm

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