PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004)

Vicki Wheelock; Teresa Tempkin; Alexandra Duffy; Amanda Martin; Lisa Mooney; Ashok Dayananthan; Lorin Scher; Sarah Farias; David Swadell; Charles DeCarli; James Brunberg; Chin-Shang Li; Yu Liu; Mark Yarborough; Julie Stout; Miriam Moscovitch-Lopatin; Steven Hersch; Kyle Fink; Geralyn Annett; Jan Nolta

PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004)

Vicki Wheelock, Teresa Tempkin, Alexandra Duffy, Amanda Martin, Lisa Mooney, Ashok Dayananthan, Lorin Scher, Sarah Farias, David Swadell, Charles DeCarli, James Brunberg, Chin-Shang Li, Yu Liu, Mark Yarborough, Julie Stout, Miriam Moscovitch-Lopatin, Steven Hersch, Kyle Fink, Geralyn Annett, Jan Nolta

Psychology

Research output: Contribution to conference › Poster › peer-review

Abstract

Objective: To describe baseline characteristics and longitudinal rate of change in multiple clinical, novel biomarker and structural MRI measures for a cohort of subjects with early-stage Huntington’s disease (HD). Background: There are no existing disease-modifying therapies for HD. Mesenchymal stem cells (MSCs) engineered to overexpress brain-derived neurotrophic factor (BDNF) is a proposed therapeutic for neuroprotection in HD. PRE-CELL is the lead-in study for a future planned Phase I trial of MSC/BDNF in HD. Design/Methods: Subjects with genetically-confirmed early-stage HD, without dementia, unstable psychiatric symptoms, contraindications to MRI or neurosurgery were assessed every 6 months for 12 - 24 months. A linear mixed effects model was used to analyze the repeated measures of selected outcome measures in the cohort. Results: Forty-two subjects have been screened and 32 enrolled (38[percnt] females, mean age of 52, range, 23 - 74). The estimated annual change rates for selected clinical measures include: UHDRS Total Functional Capacity score, -0.7884 (p-value < 0.0001); Independence Score, -6.2546 (p-value < 0.0001); Total Motor Score 9.1038 (p-value < 0.0001); HD-Quality of Life score, 17.089 (p-value = 0.0078), E-COG total score, 6.6312 (p-value = 0.0035). Rates of change in the HD Cognitive Assessment Battery will be presented. Biomarker analysis indicates a strong linear relationship between serum and CSF mutant Huntingtin protein levels (correlation of 0.87774, p-value <0.0001). Analysis of serum and CSF BDNF levels will be presented. Structural MRI analysis shows significant reduction in striatal volume detected at 6 months. Conclusions: The PRE-CELL study has enrolled a cohort of subjects with early-stage HD and has characterized the rate of change in clinical, imaging and novel serum and CSF biomarker measures. This data will be used as a baseline for subjects who are candidates for the future planned Phase 1 trial once regulatory approval has been obtained.Disclosure: Dr. Wheelock has nothing to disclose. Dr. Tempkin has received personal compensation for activities with Lundbeck Pharmaceuticals. Dr. Duffy has nothing to disclose. Dr. Martin has nothing to disclose. Dr. Mooney has nothing to disclose. Dr. Dayananthan has nothing to disclose. Dr. Scher has received personal compensation for activities with Lundbeck, Inc. as honorarium. Dr. Farias has nothing to disclose. Dr. Swadell has nothing to disclose. Dr. DeCarli has nothing to disclose. Dr. Brunberg has nothing to disclose. Dr. Li has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Yarborough has nothing to disclose. Dr. Stout has nothing to disclose. Dr. Moscovitch-Lopatin has nothing to disclose. Dr. Hersch has nothing to disclose. Dr. Fink has nothing to disclose. Dr. Annett has nothing to disclose. Dr. Nolta has nothing to disclose.Monday, April 18 2016, 3:30 pm-5:30 pm

Original language	English
Pages	244
Number of pages	1
Publication status	Published - 5 Apr 2016
Event	68th Annual American Academy of Neurology Annual Meeting - Vancouver Convention Centre, Vancouver, Canada Duration: 15 Apr 2016 → 21 Apr 2016 Conference number: 68 https://www.aan.com/conferences-community/past-conferences/2016-annual-meeting/

Conference

Conference	68th Annual American Academy of Neurology Annual Meeting
Country/Territory	Canada
City	Vancouver
Period	15/04/16 → 21/04/16
Internet address	https://www.aan.com/conferences-community/past-conferences/2016-annual-meeting/

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Wheelock, V., Tempkin, T., Duffy, A., Martin, A., Mooney, L., Dayananthan, A., Scher, L., Farias, S., Swadell, D., DeCarli, C., Brunberg, J., Li, C-S., Liu, Y., Yarborough, M., Stout, J., Moscovitch-Lopatin, M., Hersch, S., Fink, K., Annett, G., & Nolta, J. (2016). PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004). 244. Poster session presented at 68th Annual American Academy of Neurology Annual Meeting, Vancouver, British Columbia, Canada. http://www.abstractsonline.com/pp8/#!/4046/presentation/9343

Wheelock, Vicki ; Tempkin, Teresa ; Duffy, Alexandra et al. / PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004). Poster session presented at 68th Annual American Academy of Neurology Annual Meeting, Vancouver, British Columbia, Canada.1 p.

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title = "PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington{\textquoteright}s Disease (S25.004)",

abstract = "Objective: To describe baseline characteristics and longitudinal rate of change in multiple clinical, novel biomarker and structural MRI measures for a cohort of subjects with early-stage Huntington{\textquoteright}s disease (HD). Background: There are no existing disease-modifying therapies for HD. Mesenchymal stem cells (MSCs) engineered to overexpress brain-derived neurotrophic factor (BDNF) is a proposed therapeutic for neuroprotection in HD. PRE-CELL is the lead-in study for a future planned Phase I trial of MSC/BDNF in HD. Design/Methods: Subjects with genetically-confirmed early-stage HD, without dementia, unstable psychiatric symptoms, contraindications to MRI or neurosurgery were assessed every 6 months for 12 - 24 months. A linear mixed effects model was used to analyze the repeated measures of selected outcome measures in the cohort. Results: Forty-two subjects have been screened and 32 enrolled (38[percnt] females, mean age of 52, range, 23 - 74). The estimated annual change rates for selected clinical measures include: UHDRS Total Functional Capacity score, -0.7884 (p-value < 0.0001); Independence Score, -6.2546 (p-value < 0.0001); Total Motor Score 9.1038 (p-value < 0.0001); HD-Quality of Life score, 17.089 (p-value = 0.0078), E-COG total score, 6.6312 (p-value = 0.0035). Rates of change in the HD Cognitive Assessment Battery will be presented. Biomarker analysis indicates a strong linear relationship between serum and CSF mutant Huntingtin protein levels (correlation of 0.87774, p-value <0.0001). Analysis of serum and CSF BDNF levels will be presented. Structural MRI analysis shows significant reduction in striatal volume detected at 6 months. Conclusions: The PRE-CELL study has enrolled a cohort of subjects with early-stage HD and has characterized the rate of change in clinical, imaging and novel serum and CSF biomarker measures. This data will be used as a baseline for subjects who are candidates for the future planned Phase 1 trial once regulatory approval has been obtained.Disclosure: Dr. Wheelock has nothing to disclose. Dr. Tempkin has received personal compensation for activities with Lundbeck Pharmaceuticals. Dr. Duffy has nothing to disclose. Dr. Martin has nothing to disclose. Dr. Mooney has nothing to disclose. Dr. Dayananthan has nothing to disclose. Dr. Scher has received personal compensation for activities with Lundbeck, Inc. as honorarium. Dr. Farias has nothing to disclose. Dr. Swadell has nothing to disclose. Dr. DeCarli has nothing to disclose. Dr. Brunberg has nothing to disclose. Dr. Li has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Yarborough has nothing to disclose. Dr. Stout has nothing to disclose. Dr. Moscovitch-Lopatin has nothing to disclose. Dr. Hersch has nothing to disclose. Dr. Fink has nothing to disclose. Dr. Annett has nothing to disclose. Dr. Nolta has nothing to disclose.Monday, April 18 2016, 3:30 pm-5:30 pm",

author = "Vicki Wheelock and Teresa Tempkin and Alexandra Duffy and Amanda Martin and Lisa Mooney and Ashok Dayananthan and Lorin Scher and Sarah Farias and David Swadell and Charles DeCarli and James Brunberg and Chin-Shang Li and Yu Liu and Mark Yarborough and Julie Stout and Miriam Moscovitch-Lopatin and Steven Hersch and Kyle Fink and Geralyn Annett and Jan Nolta",

year = "2016",

month = apr,

day = "5",

language = "English",

pages = "244",

note = "68th Annual American Academy of Neurology Annual Meeting ; Conference date: 15-04-2016 Through 21-04-2016",

url = "https://www.aan.com/conferences-community/past-conferences/2016-annual-meeting/",

}

Wheelock, V, Tempkin, T, Duffy, A, Martin, A, Mooney, L, Dayananthan, A, Scher, L, Farias, S, Swadell, D, DeCarli, C, Brunberg, J, Li, C-S, Liu, Y, Yarborough, M, Stout, J, Moscovitch-Lopatin, M, Hersch, S, Fink, K, Annett, G & Nolta, J 2016, 'PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004)', 68th Annual American Academy of Neurology Annual Meeting, Vancouver, Canada, 15/04/16 - 21/04/16 pp. 244. <http://www.abstractsonline.com/pp8/#!/4046/presentation/9343>

PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004). / Wheelock, Vicki; Tempkin, Teresa; Duffy, Alexandra et al.
2016. 244 Poster session presented at 68th Annual American Academy of Neurology Annual Meeting, Vancouver, British Columbia, Canada.

Research output: Contribution to conference › Poster › peer-review

TY - CONF

T1 - PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004)

AU - Wheelock, Vicki

AU - Tempkin, Teresa

AU - Duffy, Alexandra

AU - Martin, Amanda

AU - Mooney, Lisa

AU - Dayananthan, Ashok

AU - Scher, Lorin

AU - Farias, Sarah

AU - Swadell, David

AU - DeCarli, Charles

AU - Brunberg, James

AU - Li, Chin-Shang

AU - Liu, Yu

AU - Yarborough, Mark

AU - Stout, Julie

AU - Moscovitch-Lopatin, Miriam

AU - Hersch, Steven

AU - Fink, Kyle

AU - Annett, Geralyn

AU - Nolta, Jan

N1 - Conference code: 68

PY - 2016/4/5

Y1 - 2016/4/5

N2 - Objective: To describe baseline characteristics and longitudinal rate of change in multiple clinical, novel biomarker and structural MRI measures for a cohort of subjects with early-stage Huntington’s disease (HD). Background: There are no existing disease-modifying therapies for HD. Mesenchymal stem cells (MSCs) engineered to overexpress brain-derived neurotrophic factor (BDNF) is a proposed therapeutic for neuroprotection in HD. PRE-CELL is the lead-in study for a future planned Phase I trial of MSC/BDNF in HD. Design/Methods: Subjects with genetically-confirmed early-stage HD, without dementia, unstable psychiatric symptoms, contraindications to MRI or neurosurgery were assessed every 6 months for 12 - 24 months. A linear mixed effects model was used to analyze the repeated measures of selected outcome measures in the cohort. Results: Forty-two subjects have been screened and 32 enrolled (38[percnt] females, mean age of 52, range, 23 - 74). The estimated annual change rates for selected clinical measures include: UHDRS Total Functional Capacity score, -0.7884 (p-value < 0.0001); Independence Score, -6.2546 (p-value < 0.0001); Total Motor Score 9.1038 (p-value < 0.0001); HD-Quality of Life score, 17.089 (p-value = 0.0078), E-COG total score, 6.6312 (p-value = 0.0035). Rates of change in the HD Cognitive Assessment Battery will be presented. Biomarker analysis indicates a strong linear relationship between serum and CSF mutant Huntingtin protein levels (correlation of 0.87774, p-value <0.0001). Analysis of serum and CSF BDNF levels will be presented. Structural MRI analysis shows significant reduction in striatal volume detected at 6 months. Conclusions: The PRE-CELL study has enrolled a cohort of subjects with early-stage HD and has characterized the rate of change in clinical, imaging and novel serum and CSF biomarker measures. This data will be used as a baseline for subjects who are candidates for the future planned Phase 1 trial once regulatory approval has been obtained.Disclosure: Dr. Wheelock has nothing to disclose. Dr. Tempkin has received personal compensation for activities with Lundbeck Pharmaceuticals. Dr. Duffy has nothing to disclose. Dr. Martin has nothing to disclose. Dr. Mooney has nothing to disclose. Dr. Dayananthan has nothing to disclose. Dr. Scher has received personal compensation for activities with Lundbeck, Inc. as honorarium. Dr. Farias has nothing to disclose. Dr. Swadell has nothing to disclose. Dr. DeCarli has nothing to disclose. Dr. Brunberg has nothing to disclose. Dr. Li has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Yarborough has nothing to disclose. Dr. Stout has nothing to disclose. Dr. Moscovitch-Lopatin has nothing to disclose. Dr. Hersch has nothing to disclose. Dr. Fink has nothing to disclose. Dr. Annett has nothing to disclose. Dr. Nolta has nothing to disclose.Monday, April 18 2016, 3:30 pm-5:30 pm

AB - Objective: To describe baseline characteristics and longitudinal rate of change in multiple clinical, novel biomarker and structural MRI measures for a cohort of subjects with early-stage Huntington’s disease (HD). Background: There are no existing disease-modifying therapies for HD. Mesenchymal stem cells (MSCs) engineered to overexpress brain-derived neurotrophic factor (BDNF) is a proposed therapeutic for neuroprotection in HD. PRE-CELL is the lead-in study for a future planned Phase I trial of MSC/BDNF in HD. Design/Methods: Subjects with genetically-confirmed early-stage HD, without dementia, unstable psychiatric symptoms, contraindications to MRI or neurosurgery were assessed every 6 months for 12 - 24 months. A linear mixed effects model was used to analyze the repeated measures of selected outcome measures in the cohort. Results: Forty-two subjects have been screened and 32 enrolled (38[percnt] females, mean age of 52, range, 23 - 74). The estimated annual change rates for selected clinical measures include: UHDRS Total Functional Capacity score, -0.7884 (p-value < 0.0001); Independence Score, -6.2546 (p-value < 0.0001); Total Motor Score 9.1038 (p-value < 0.0001); HD-Quality of Life score, 17.089 (p-value = 0.0078), E-COG total score, 6.6312 (p-value = 0.0035). Rates of change in the HD Cognitive Assessment Battery will be presented. Biomarker analysis indicates a strong linear relationship between serum and CSF mutant Huntingtin protein levels (correlation of 0.87774, p-value <0.0001). Analysis of serum and CSF BDNF levels will be presented. Structural MRI analysis shows significant reduction in striatal volume detected at 6 months. Conclusions: The PRE-CELL study has enrolled a cohort of subjects with early-stage HD and has characterized the rate of change in clinical, imaging and novel serum and CSF biomarker measures. This data will be used as a baseline for subjects who are candidates for the future planned Phase 1 trial once regulatory approval has been obtained.Disclosure: Dr. Wheelock has nothing to disclose. Dr. Tempkin has received personal compensation for activities with Lundbeck Pharmaceuticals. Dr. Duffy has nothing to disclose. Dr. Martin has nothing to disclose. Dr. Mooney has nothing to disclose. Dr. Dayananthan has nothing to disclose. Dr. Scher has received personal compensation for activities with Lundbeck, Inc. as honorarium. Dr. Farias has nothing to disclose. Dr. Swadell has nothing to disclose. Dr. DeCarli has nothing to disclose. Dr. Brunberg has nothing to disclose. Dr. Li has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Yarborough has nothing to disclose. Dr. Stout has nothing to disclose. Dr. Moscovitch-Lopatin has nothing to disclose. Dr. Hersch has nothing to disclose. Dr. Fink has nothing to disclose. Dr. Annett has nothing to disclose. Dr. Nolta has nothing to disclose.Monday, April 18 2016, 3:30 pm-5:30 pm

M3 - Poster

SP - 244

T2 - 68th Annual American Academy of Neurology Annual Meeting

Y2 - 15 April 2016 through 21 April 2016

ER -

Wheelock V, Tempkin T, Duffy A, Martin A, Mooney L, Dayananthan A et al.. PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004). 2016. Poster session presented at 68th Annual American Academy of Neurology Annual Meeting, Vancouver, British Columbia, Canada.