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Davunetide (AL-108) in Predicted Tauopathies - Pilot Study

Primary Purpose

Predicted Tauopathies, Including, Progressive Supranuclear Palsy, Frontotemporal Dementia With Parkinsonism Linked to Chromosome 17

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
davunetide (AL-108, NAP)
Placebo nasal spray
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Predicted Tauopathies, Including focused on measuring Frontotemporal Dementia, Corticobasal Degeneration, Progressive Nonfluent Aphasia, Progressive Supranuclear Palsy, FTLD, FTD, PNFA, CBD, PSP, Predicted tauopathies, including:, Progressive Supranuclear Palsy (PSP), (CBS), Progressive Nonfluent Aphasia (PNFA)

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. A probable tauopathy defined as:

    • Probable or possible progressive supranuclear palsy (PSP) defined as:

      1. at least a 12-month history of:

        • postural instability or falls during the first 3 years that symptoms are present and
        • prominent decreased saccade velocity or supranuclear ophthalmoplegia;
      2. age at symptom onset ≥ 40 years by history; and
      3. an akinetic-rigid syndrome with prominent axial rigidity.

    OR,

    • Progressive nonfluent aphasia (PNFA)defined as:

      1. at least a 6-month history of difficulty with expressive speech characterized by at least 3 of the following:

        • apraxia of speech,
        • speech hesitancy,
        • labored speech,
        • word finding difficulty, or
        • agrammatism; and
      2. the symptoms above are the subject's principal neurological deficit and the symptoms constituted the initial clinical presentation.

    OR,

    • Corticobasal Degeneration syndrome (CBS) defined as:

      1. at least a 6-month history of progressive cortical dysfunction evidenced by at least one of the following:

        • ideomotor apraxia,
        • alien limb phenomenon,
        • cortical sensory loss,
        • focal or asymmetric myoclonus, or
        • apraxia of speech /nonfluent aphasia; and
      2. at least a 6-month history of progressive extrapyramidal dysfunction evidenced by at least one of the following:

        • focal or asymmetrical rigidity (limb or axial) or asymmetrical dystonia (limb or axial); and
        • lacking prominent and sustained L-dopa response.

    OR

    • Frontotemporal Dementia with Parkinsonism linked to Chromosome 17 (FTDP-17): Motor, cognitive or behavioral dysfunction, as defined below associated with a previously demonstrated mutation of the MAPT gene, and meets criteria for PNFA, CBS or PSP as defined above, or CDR-FTLD ≥ 1.0.
  2. Documented age 40-85 years at the time of the onset of symptoms associated with the neurological deficits described in inclusion criterion 1.
  3. Judged by investigator to be able to comply with neuropsychological evaluation at baseline.
  4. Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand and speak local language fluently in order to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 times per week for one hour) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study.
  5. FTLD Modified Hachinski score ≤ 3.(Knopman et al., 2008) This modified Hachinski will not include the focal neurological signs, symptoms or pseudobulbar affect questions, given the prominence of all three in CBS/PSP.
  6. MMSE ≥ 15 at Visit 1.
  7. Written informed consent provided by both subject and caregiver who are both fluent English speakers.
  8. Subject resides outside a skilled nursing facility or dementia care facility. Residence in an assisted living facility is allowed.
  9. If the subject is receiving levodopa/carbidopa, a dopamine agonist, COMT inhibitor or other Parkinson's medication the dose must have been stable for at least 120 days prior to Visit 1 and must remain stable for the duration of the study.
  10. Able to tolerate MRI scan during screening without use of sedation.
  11. Able to ambulate with or without assistance.

Exclusion Criteria:

  1. Insufficient fluency in local language to complete neuropsychological and functional assessments.
  2. A diagnosis of Amyotrophic Lateral Sclerosis or other motor neuron disease.
  3. Any of the following:

    • Abrupt onset of symptoms defined in inclusion criteria 1 associated with ictal events,
    • Head trauma related to onset of symptoms defined in inclusion criteria 1,
    • Severe amnesia within 6 months of the symptoms defined in inclusion criteria 1,
    • Cerebellar ataxia,
    • Choreoathetosis,
    • Early, symptomatic autonomic dysfunction, or
    • Tremor at rest.
  4. History of other significant neurological or psychiatric disorders including, but not limited to, Alzheimer's disease, dementia with Lewy bodies, Prion disease, stroke, Parkinson's disease, any psychotic disorder, severe bipolar or unipolar depression, seizure disorder, tumor or other space-occupying lesion, or head injury with loss of consciousness within past 20 years temporally related to onset of symptoms.
  5. Within 4 weeks of screening or during the course of the study, concurrent treatment with memantine (stable dose memantine, greater than 6 months is allowed), acetylcholinesterase inhibitors, antipsychotic agents or mood stabilizers (valproate, lithium, etc.) or benzodiazepines (other than temazepam or zolpidem).
  6. Treatment with lithium, methylene blue, tramiprosate, ketone bodies, Dimebon or any putative disease-modifying agent directed at tau within 90 days of screening.
  7. A history of alcohol or substance abuse within 1 year prior to screening and deemed to be clinically significant by the site investigator.
  8. Any malignancy (other than non-metastatic basal cell carcinoma of the skin) within 5 years of Visit 1 or current clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. For the non-cancer conditions, if the condition has been stable for at least the past year and is judged by the site investigator not to interfere with the patient's participation in the study, the patient may be included.
  9. Clinically significant lab abnormalities at screening, including creatinine ≥ 2.5 mg/dL, vitamin B12 below laboratory normal reference range, or TSH above laboratory normal reference range.
  10. Systolic blood pressure greater than 180 or less than 90 mm Hg. Diastolic blood pressure greater than 105 or less than 50 mm Hg.
  11. ECG abnormal at screening and judged to be clinically significant by the site investigator.
  12. Treatment with any investigational drugs or device or participation in an investigational drug study within 60 days of screening.
  13. Known history of serum or plasma progranulin level < 110.9 ng/mL.
  14. Known presence of known disease-associated mutation in TDP-43, PGRN, CHMPB2 or VCP genes or any other FTLD causative genes not associated with underlying tau pathology (eg. Chr. 9 associated FTD).
  15. History of deep brain stimulator surgery other than sham surgery for DBS clinical trial.
  16. History of early, prominent REM behavior disorder.
  17. Women of childbearing potential who are not using at least two forms of medically recognized contraception.
  18. An employee or relative of an employee of Allon Therapeutics
  19. Significant anatomical nasal abnormality (e.g., septal deviation obstructing airflow to at least one nostril or septal perforation) or history of nasal turbinate surgery.
  20. History of a clinically significant medical condition that that would interfere with the subject's ability to comply with study instructions, would place the subject at increased risk, or might confound the interpretation of the study results.
  21. Contraindication to MRI examination for any reason (eg., severe claustrophobia, ferromagnetic metal in body, etc.).
  22. Structural abnormality on MRI within 2 years of baseline that precludes diagnosis of PSP, CBS or PNFA, such as cortical infarct in brain region that might account for subject's symptoms.
  23. In subjects receiving anti-Parkinson's Disease medication at the time of screening, in the opinion of the investigator substantial worsening of motor signs or symptoms compared to normal functioning following overnight withdrawal of the anti-Parkinson medication.
  24. Subject not willing to attempt LP.

Sites / Locations

  • University of California, San Francisco (UCSF)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

davunetide (Al-108, NAP) nasal spray

Placebo nasal spray

Arm Description

Subjects will be randomized 2:1 (drug:placebo). Subjects will receive twice daily treatment with either davunetide 15 mg or placebo. Davunetide and placebo will be administered intranasally with a multi-dispensing, metered nasal spray pump device.

Outcomes

Primary Outcome Measures

Safety evaluations will be performed by recording clinical adverse events at each study visit. Clinical laboratory, ECGs, physical examinations will be conducted.

Secondary Outcome Measures

PSP Rating Scale
Clinician's Global Impression (CGI-ds)
Schwab and England Activities of Daily Living scale (SEADL)
MRI brain ventricular volume
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Unified Parkinson's Disease Rating Scale (UPDRS)
Neuropsychiatric Inventory (NPI)
Geriatric Depression Scale (GDS)
CSF biomarkers will assess total tau, phosphorylated tau, and amyloid beta peptide (1-42)
Saccadic Eye movements - vertical and horizontal total saccade time
Clinical Dementia Rating (CDR)
Functional Activities Questionnaire (FAQ)

Full Information

First Posted
January 21, 2010
Last Updated
April 3, 2019
Sponsor
University of California, San Francisco
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1. Study Identification

Unique Protocol Identification Number
NCT01056965
Brief Title
Davunetide (AL-108) in Predicted Tauopathies - Pilot Study
Official Title
A 12 Week Randomized, Double Blind, Placebo-Controlled Pilot Study of Davunetide (NAP, AL-108) in Predicted Tauopathies
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Francisco

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of the study is to obtain preliminary safety and tolerability data with davunetide (NAP, AL-108) in patients with a tauopathy (frontotemporal lobar degeneration [FTLD] with predicted tau pathology, corticobasal degeneration syndrome [CBS] or progressive supranuclear palsy [PSP]). The secondary objectives of this study are to obtain preliminary data on short term changes (at 12 weeks) in a variety of clinical, functional and biomarker measurements from baseline, including cerebrospinal fluid (CSF) tau levels, eye movements, and brain MRI measurements.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Predicted Tauopathies, Including, Progressive Supranuclear Palsy, Frontotemporal Dementia With Parkinsonism Linked to Chromosome 17, Corticobasal Degeneration Syndrome, Progressive Nonfluent Aphasia
Keywords
Frontotemporal Dementia, Corticobasal Degeneration, Progressive Nonfluent Aphasia, Progressive Supranuclear Palsy, FTLD, FTD, PNFA, CBD, PSP, Predicted tauopathies, including:, Progressive Supranuclear Palsy (PSP), (CBS), Progressive Nonfluent Aphasia (PNFA)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
davunetide (Al-108, NAP) nasal spray
Arm Type
Experimental
Arm Description
Subjects will be randomized 2:1 (drug:placebo). Subjects will receive twice daily treatment with either davunetide 15 mg or placebo. Davunetide and placebo will be administered intranasally with a multi-dispensing, metered nasal spray pump device.
Arm Title
Placebo nasal spray
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
davunetide (AL-108, NAP)
Other Intervention Name(s)
AL-108, NAP
Intervention Description
Subjects will be randomized 2:1 (drug:placebo). Subjects will receive twice daily treatment with davunetide 15 mg administered intranasally.
Intervention Type
Drug
Intervention Name(s)
Placebo nasal spray
Intervention Description
Subjects will be randomized 2:1 (drug:placebo). Subjects will receive twice daily treatment with placebo administered intranasally.
Primary Outcome Measure Information:
Title
Safety evaluations will be performed by recording clinical adverse events at each study visit. Clinical laboratory, ECGs, physical examinations will be conducted.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
PSP Rating Scale
Time Frame
12 weeks
Title
Clinician's Global Impression (CGI-ds)
Time Frame
12 weeks
Title
Schwab and England Activities of Daily Living scale (SEADL)
Time Frame
12 weeks
Title
MRI brain ventricular volume
Time Frame
12 weeks
Title
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time Frame
12 weeks
Title
Unified Parkinson's Disease Rating Scale (UPDRS)
Time Frame
12 weeks
Title
Neuropsychiatric Inventory (NPI)
Time Frame
12 weeks
Title
Geriatric Depression Scale (GDS)
Time Frame
12 weeks
Title
CSF biomarkers will assess total tau, phosphorylated tau, and amyloid beta peptide (1-42)
Time Frame
12 weeks
Title
Saccadic Eye movements - vertical and horizontal total saccade time
Time Frame
12 weeks
Title
Clinical Dementia Rating (CDR)
Time Frame
12 weeeks
Title
Functional Activities Questionnaire (FAQ)
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A probable tauopathy defined as: Probable or possible progressive supranuclear palsy (PSP) defined as: at least a 12-month history of: postural instability or falls during the first 3 years that symptoms are present and prominent decreased saccade velocity or supranuclear ophthalmoplegia; age at symptom onset ≥ 40 years by history; and an akinetic-rigid syndrome with prominent axial rigidity. OR, Progressive nonfluent aphasia (PNFA)defined as: at least a 6-month history of difficulty with expressive speech characterized by at least 3 of the following: apraxia of speech, speech hesitancy, labored speech, word finding difficulty, or agrammatism; and the symptoms above are the subject's principal neurological deficit and the symptoms constituted the initial clinical presentation. OR, Corticobasal Degeneration syndrome (CBS) defined as: at least a 6-month history of progressive cortical dysfunction evidenced by at least one of the following: ideomotor apraxia, alien limb phenomenon, cortical sensory loss, focal or asymmetric myoclonus, or apraxia of speech /nonfluent aphasia; and at least a 6-month history of progressive extrapyramidal dysfunction evidenced by at least one of the following: focal or asymmetrical rigidity (limb or axial) or asymmetrical dystonia (limb or axial); and lacking prominent and sustained L-dopa response. OR Frontotemporal Dementia with Parkinsonism linked to Chromosome 17 (FTDP-17): Motor, cognitive or behavioral dysfunction, as defined below associated with a previously demonstrated mutation of the MAPT gene, and meets criteria for PNFA, CBS or PSP as defined above, or CDR-FTLD ≥ 1.0. Documented age 40-85 years at the time of the onset of symptoms associated with the neurological deficits described in inclusion criterion 1. Judged by investigator to be able to comply with neuropsychological evaluation at baseline. Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand and speak local language fluently in order to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 times per week for one hour) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study. FTLD Modified Hachinski score ≤ 3.(Knopman et al., 2008) This modified Hachinski will not include the focal neurological signs, symptoms or pseudobulbar affect questions, given the prominence of all three in CBS/PSP. MMSE ≥ 15 at Visit 1. Written informed consent provided by both subject and caregiver who are both fluent English speakers. Subject resides outside a skilled nursing facility or dementia care facility. Residence in an assisted living facility is allowed. If the subject is receiving levodopa/carbidopa, a dopamine agonist, COMT inhibitor or other Parkinson's medication the dose must have been stable for at least 120 days prior to Visit 1 and must remain stable for the duration of the study. Able to tolerate MRI scan during screening without use of sedation. Able to ambulate with or without assistance. Exclusion Criteria: Insufficient fluency in local language to complete neuropsychological and functional assessments. A diagnosis of Amyotrophic Lateral Sclerosis or other motor neuron disease. Any of the following: Abrupt onset of symptoms defined in inclusion criteria 1 associated with ictal events, Head trauma related to onset of symptoms defined in inclusion criteria 1, Severe amnesia within 6 months of the symptoms defined in inclusion criteria 1, Cerebellar ataxia, Choreoathetosis, Early, symptomatic autonomic dysfunction, or Tremor at rest. History of other significant neurological or psychiatric disorders including, but not limited to, Alzheimer's disease, dementia with Lewy bodies, Prion disease, stroke, Parkinson's disease, any psychotic disorder, severe bipolar or unipolar depression, seizure disorder, tumor or other space-occupying lesion, or head injury with loss of consciousness within past 20 years temporally related to onset of symptoms. Within 4 weeks of screening or during the course of the study, concurrent treatment with memantine (stable dose memantine, greater than 6 months is allowed), acetylcholinesterase inhibitors, antipsychotic agents or mood stabilizers (valproate, lithium, etc.) or benzodiazepines (other than temazepam or zolpidem). Treatment with lithium, methylene blue, tramiprosate, ketone bodies, Dimebon or any putative disease-modifying agent directed at tau within 90 days of screening. A history of alcohol or substance abuse within 1 year prior to screening and deemed to be clinically significant by the site investigator. Any malignancy (other than non-metastatic basal cell carcinoma of the skin) within 5 years of Visit 1 or current clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. For the non-cancer conditions, if the condition has been stable for at least the past year and is judged by the site investigator not to interfere with the patient's participation in the study, the patient may be included. Clinically significant lab abnormalities at screening, including creatinine ≥ 2.5 mg/dL, vitamin B12 below laboratory normal reference range, or TSH above laboratory normal reference range. Systolic blood pressure greater than 180 or less than 90 mm Hg. Diastolic blood pressure greater than 105 or less than 50 mm Hg. ECG abnormal at screening and judged to be clinically significant by the site investigator. Treatment with any investigational drugs or device or participation in an investigational drug study within 60 days of screening. Known history of serum or plasma progranulin level < 110.9 ng/mL. Known presence of known disease-associated mutation in TDP-43, PGRN, CHMPB2 or VCP genes or any other FTLD causative genes not associated with underlying tau pathology (eg. Chr. 9 associated FTD). History of deep brain stimulator surgery other than sham surgery for DBS clinical trial. History of early, prominent REM behavior disorder. Women of childbearing potential who are not using at least two forms of medically recognized contraception. An employee or relative of an employee of Allon Therapeutics Significant anatomical nasal abnormality (e.g., septal deviation obstructing airflow to at least one nostril or septal perforation) or history of nasal turbinate surgery. History of a clinically significant medical condition that that would interfere with the subject's ability to comply with study instructions, would place the subject at increased risk, or might confound the interpretation of the study results. Contraindication to MRI examination for any reason (eg., severe claustrophobia, ferromagnetic metal in body, etc.). Structural abnormality on MRI within 2 years of baseline that precludes diagnosis of PSP, CBS or PNFA, such as cortical infarct in brain region that might account for subject's symptoms. In subjects receiving anti-Parkinson's Disease medication at the time of screening, in the opinion of the investigator substantial worsening of motor signs or symptoms compared to normal functioning following overnight withdrawal of the anti-Parkinson medication. Subject not willing to attempt LP.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adam L. Boxer, M.D., Ph.D.
Organizational Affiliation
UCSF Memory and Aging Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco (UCSF)
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-1207
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17589313
Citation
Antoniades CA, Altham PM, Mason SL, Barker RA, Carpenter R. Saccadometry: a new tool for evaluating presymptomatic Huntington patients. Neuroreport. 2007 Jul 16;18(11):1133-6. doi: 10.1097/WNR.0b013e32821c560d.
Results Reference
background
PubMed Identifier
20477368
Citation
Antoniades CA, Bak TH, Carpenter RH, Hodges JR, Barker RA. Diagnostic potential of saccadometry in progressive supranuclear palsy. Biomark Med. 2007 Dec;1(4):487-90. doi: 10.2217/17520363.1.4.487.
Results Reference
background
PubMed Identifier
10037502
Citation
Bassan M, Zamostiano R, Davidson A, Pinhasov A, Giladi E, Perl O, Bassan H, Blat C, Gibney G, Glazner G, Brenneman DE, Gozes I. Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. J Neurochem. 1999 Mar;72(3):1283-93. doi: 10.1046/j.1471-4159.1999.0721283.x.
Results Reference
background
PubMed Identifier
19029129
Citation
Bensimon G, Ludolph A, Agid Y, Vidailhet M, Payan C, Leigh PN; NNIPPS Study Group. Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain. 2009 Jan;132(Pt 1):156-71. doi: 10.1093/brain/awn291. Epub 2008 Nov 23.
Results Reference
background
PubMed Identifier
12833363
Citation
Boeve BF, Lang AE, Litvan I. Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol. 2003;54 Suppl 5:S15-9. doi: 10.1002/ana.10570. No abstract available.
Results Reference
background
PubMed Identifier
8636410
Citation
Brenneman DE, Gozes I. A femtomolar-acting neuroprotective peptide. J Clin Invest. 1996 May 15;97(10):2299-307. doi: 10.1172/JCI118672.
Results Reference
background
PubMed Identifier
17579875
Citation
Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM; Consortium for Frontotemporal Lobar Degeneration. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol. 2007 Jul;114(1):5-22. doi: 10.1007/s00401-007-0237-2. Epub 2007 Jun 20.
Results Reference
background
PubMed Identifier
9153155
Citation
Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997 May;48(5 Suppl 6):S10-6. doi: 10.1212/wnl.48.5_suppl_6.10s.
Results Reference
background
PubMed Identifier
19491678
Citation
Detre JA, Wang J, Wang Z, Rao H. Arterial spin-labeled perfusion MRI in basic and clinical neuroscience. Curr Opin Neurol. 2009 Aug;22(4):348-55. doi: 10.1097/WCO.0b013e32832d9505.
Results Reference
background
PubMed Identifier
10525997
Citation
Dickson DW. Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration. J Neurol. 1999 Sep;246 Suppl 2:II6-15. doi: 10.1007/BF03161076.
Results Reference
background
Citation
Fahn S, Elton RL, Committee. Unified Parkinson's Disease Rating Scale. In: Fahn S, Marsden CD, Calne D and Goldstein M, editors. Recent Developments in Parkinson's Disease. Vol 2. Florham Park, NJ: Macmillan Health-care Information, 1987: 153-163.
Results Reference
background
PubMed Identifier
16845437
Citation
Furman S, Steingart RA, Mandel S, Hauser JM, Brenneman DE, Gozes I. Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes. Neuron Glia Biol. 2004 Aug;1(3):193-9. doi: 10.1017/S1740925X05000013.
Results Reference
background
PubMed Identifier
18362099
Citation
Garbutt S, Matlin A, Hellmuth J, Schenk AK, Johnson JK, Rosen H, Dean D, Kramer J, Neuhaus J, Miller BL, Lisberger SG, Boxer AL. Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease. Brain. 2008 May;131(Pt 5):1268-81. doi: 10.1093/brain/awn047. Epub 2008 Mar 24.
Results Reference
background
PubMed Identifier
17952637
Citation
Giladi E, Hill JM, Dresner E, Stack CM, Gozes I. Vasoactive intestinal peptide (VIP) regulates activity-dependent neuroprotective protein (ADNP) expression in vivo. J Mol Neurosci. 2007;33(3):278-83. doi: 10.1007/s12031-007-9003-0. Epub 2007 Oct 2.
Results Reference
background
PubMed Identifier
17405767
Citation
Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007 Jun;130(Pt 6):1552-65. doi: 10.1093/brain/awm032. Epub 2007 Apr 2.
Results Reference
background
PubMed Identifier
10854037
Citation
Gozes I, Brenneman DE. A new concept in the pharmacology of neuroprotection. J Mol Neurosci. 2000 Feb-Apr;14(1-2):61-8. doi: 10.1385/JMN:14:1-2:061.
Results Reference
background
PubMed Identifier
19091000
Citation
Gozes I, Divinski I, Piltzer I. NAP and D-SAL: neuroprotection against the beta amyloid peptide (1-42). BMC Neurosci. 2008 Dec 10;9 Suppl 3(Suppl 3):S3. doi: 10.1186/1471-2202-9-S3-S3.
Results Reference
background
PubMed Identifier
14501014
Citation
Gozes I, Divinsky I, Pilzer I, Fridkin M, Brenneman DE, Spier AD. From vasoactive intestinal peptide (VIP) through activity-dependent neuroprotective protein (ADNP) to NAP: a view of neuroprotection and cell division. J Mol Neurosci. 2003;20(3):315-22. doi: 10.1385/JMN:20:3:315.
Results Reference
background
PubMed Identifier
10519911
Citation
Gozes I, Fridkinb M, Hill JM, Brenneman DE. Pharmaceutical VIP: prospects and problems. Curr Med Chem. 1999 Nov;6(11):1019-34.
Results Reference
background
PubMed Identifier
16614735
Citation
Gozes I, Morimoto BH, Tiong J, Fox A, Sutherland K, Dangoor D, Holser-Cochav M, Vered K, Newton P, Aisen PS, Matsuoka Y, van Dyck CH, Thal L. NAP: research and development of a peptide derived from activity-dependent neuroprotective protein (ADNP). CNS Drug Rev. 2005 Winter;11(4):353-68. doi: 10.1111/j.1527-3458.2005.tb00053.x.
Results Reference
background
PubMed Identifier
17545742
Citation
Kertesz A, Blair M, McMonagle P, Munoz DG. The diagnosis and course of frontotemporal dementia. Alzheimer Dis Assoc Disord. 2007 Apr-Jun;21(2):155-63. doi: 10.1097/WAD.0b013e31806547eb.
Results Reference
background
PubMed Identifier
18829698
Citation
Knopman DS, Kramer JH, Boeve BF, Caselli RJ, Graff-Radford NR, Mendez MF, Miller BL, Mercaldo N. Development of methodology for conducting clinical trials in frontotemporal lobar degeneration. Brain. 2008 Nov;131(Pt 11):2957-68. doi: 10.1093/brain/awn234. Epub 2008 Oct 1.
Results Reference
background
PubMed Identifier
11520930
Citation
Lee VM, Goedert M, Trojanowski JQ. Neurodegenerative tauopathies. Annu Rev Neurosci. 2001;24:1121-59. doi: 10.1146/annurev.neuro.24.1.1121.
Results Reference
background
PubMed Identifier
8710059
Citation
Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996 Jul;47(1):1-9. doi: 10.1212/wnl.47.1.1.
Results Reference
background
PubMed Identifier
19015862
Citation
Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, Kamphorst W, Revesz T, Rozemuller AJ, Kumar-Singh S, Akiyama H, Baborie A, Spina S, Dickson DW, Trojanowski JQ, Mann DM. Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol. 2009 Jan;117(1):15-8. doi: 10.1007/s00401-008-0460-5. Epub 2008 Nov 18. No abstract available.
Results Reference
background
PubMed Identifier
17478890
Citation
Matsuoka Y, Gray AJ, Hirata-Fukae C, Minami SS, Waterhouse EG, Mattson MP, LaFerla FM, Gozes I, Aisen PS. Intranasal NAP administration reduces accumulation of amyloid peptide and tau hyperphosphorylation in a transgenic mouse model of Alzheimer's disease at early pathological stage. J Mol Neurosci. 2007;31(2):165-70. doi: 10.1385/jmn/31:02:165.
Results Reference
background
PubMed Identifier
18199809
Citation
Matsuoka Y, Jouroukhin Y, Gray AJ, Ma L, Hirata-Fukae C, Li HF, Feng L, Lecanu L, Walker BR, Planel E, Arancio O, Gozes I, Aisen PS. A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer's disease. J Pharmacol Exp Ther. 2008 Apr;325(1):146-53. doi: 10.1124/jpet.107.130526. Epub 2008 Jan 16.
Results Reference
background
PubMed Identifier
9855500
Citation
Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998 Dec;51(6):1546-54. doi: 10.1212/wnl.51.6.1546.
Results Reference
background
PubMed Identifier
12895417
Citation
Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003 Jul 31;39(3):409-21. doi: 10.1016/s0896-6273(03)00434-3.
Results Reference
background
PubMed Identifier
12888219
Citation
Pinhasov A, Mandel S, Torchinsky A, Giladi E, Pittel Z, Goldsweig AM, Servoss SJ, Brenneman DE, Gozes I. Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Brain Res Dev Brain Res. 2003 Aug 12;144(1):83-90. doi: 10.1016/s0165-3806(03)00162-7.
Results Reference
background
PubMed Identifier
11164280
Citation
Reed LA, Wszolek ZK, Hutton M. Phenotypic correlations in FTDP-17. Neurobiol Aging. 2001 Jan-Feb;22(1):89-107. doi: 10.1016/s0197-4580(00)00202-5.
Results Reference
background
PubMed Identifier
10720270
Citation
Rivaud-Pechoux S, Vidailhet M, Gallouedec G, Litvan I, Gaymard B, Pierrot-Deseilligny C. Longitudinal ocular motor study in corticobasal degeneration and progressive supranuclear palsy. Neurology. 2000 Mar 14;54(5):1029-32. doi: 10.1212/wnl.54.5.1029.
Results Reference
background
PubMed Identifier
18490011
Citation
Rosenmann H, Grigoriadis N, Eldar-Levy H, Avital A, Rozenstein L, Touloumi O, Behar L, Ben-Hur T, Avraham Y, Berry E, Segal M, Ginzburg I, Abramsky O. A novel transgenic mouse expressing double mutant tau driven by its natural promoter exhibits tauopathy characteristics. Exp Neurol. 2008 Jul;212(1):71-84. doi: 10.1016/j.expneurol.2008.03.007. Epub 2008 Mar 21.
Results Reference
background
PubMed Identifier
8602756
Citation
Rottach KG, Riley DE, DiScenna AO, Zivotofsky AZ, Leigh RJ. Dynamic properties of horizontal and vertical eye movements in parkinsonian syndromes. Ann Neurol. 1996 Mar;39(3):368-77. doi: 10.1002/ana.410390314.
Results Reference
background
PubMed Identifier
9236949
Citation
Schneider LS, Olin JT, Doody RS, Clark CM, Morris JC, Reisberg B, Schmitt FA, Grundman M, Thomas RG, Ferris SH. Validity and reliability of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S22-32. doi: 10.1097/00002093-199700112-00004.
Results Reference
background
Citation
Schwab R, England A. Projecton technique for evaluating surgery in Parkinson's disease. In: Gillingham F and Donaldson M, editors. Third Symposium on Parkinson's Disease Research. Edinburgh, Scotland: ES Livingston, 1969.
Results Reference
background
PubMed Identifier
19376066
Citation
Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009 Apr 16;62(1):42-52. doi: 10.1016/j.neuron.2009.03.024.
Results Reference
background
PubMed Identifier
19264130
Citation
Shiryaev N, Jouroukhin Y, Giladi E, Polyzoidou E, Grigoriadis NC, Rosenmann H, Gozes I. NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model. Neurobiol Dis. 2009 May;34(2):381-8. doi: 10.1016/j.nbd.2009.02.011. Epub 2009 Mar 2.
Results Reference
background
PubMed Identifier
15800376
Citation
Smith-Swintosky VL, Gozes I, Brenneman DE, D'Andrea MR, Plata-Salaman CR. Activity-dependent neurotrophic factor-9 and NAP promote neurite outgrowth in rat hippocampal and cortical cultures. J Mol Neurosci. 2005;25(3):225-38. doi: 10.1385/JMN:25:3:225.
Results Reference
background
PubMed Identifier
14107684
Citation
STEELE JC, RICHARDSON JC, OLSZEWSKI J. PROGRESSIVE SUPRANUCLEAR PALSY. A HETEROGENEOUS DEGENERATION INVOLVING THE BRAIN STEM, BASAL GANGLIA AND CEREBELLUM WITH VERTICAL GAZE AND PSEUDOBULBAR PALSY, NUCHAL DYSTONIA AND DEMENTIA. Arch Neurol. 1964 Apr;10:333-59. doi: 10.1001/archneur.1964.00460160003001. No abstract available.
Results Reference
background
PubMed Identifier
11303778
Citation
Steingart RA, Solomon B, Brenneman DE, Fridkin M, Gozes I. VIP and peptides related to activity-dependent neurotrophic factor protect PC12 cells against oxidative stress. J Mol Neurosci. 2000 Dec;15(3):137-45. doi: 10.1385/JMN:15:3:137.
Results Reference
background
PubMed Identifier
8154868
Citation
Vidailhet M, Rivaud S, Gouider-Khouja N, Pillon B, Bonnet AM, Gaymard B, Agid Y, Pierrot-Deseilligny C. Eye movements in parkinsonian syndromes. Ann Neurol. 1994 Apr;35(4):420-6. doi: 10.1002/ana.410350408.
Results Reference
background
PubMed Identifier
17720885
Citation
Vulih-Shultzman I, Pinhasov A, Mandel S, Grigoriadis N, Touloumi O, Pittel Z, Gozes I. Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. J Pharmacol Exp Ther. 2007 Nov;323(2):438-49. doi: 10.1124/jpet.107.129551. Epub 2007 Aug 24.
Results Reference
background
PubMed Identifier
7183759
Citation
Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983;17(1):37-49. doi: 10.1016/0022-3956(82)90033-4.
Results Reference
background
PubMed Identifier
11013255
Citation
Zamostiano R, Pinhasov A, Gelber E, Steingart RA, Seroussi E, Giladi E, Bassan M, Wollman Y, Eyre HJ, Mulley JC, Brenneman DE, Gozes I. Cloning and characterization of the human activity-dependent neuroprotective protein. J Biol Chem. 2001 Jan 5;276(1):708-14. doi: 10.1074/jbc.M007416200.
Results Reference
background
PubMed Identifier
15518891
Citation
Zusev M, Gozes I. Differential regulation of activity-dependent neuroprotective protein in rat astrocytes by VIP and PACAP. Regul Pept. 2004 Dec 15;123(1-3):33-41. doi: 10.1016/j.regpep.2004.05.021.
Results Reference
background

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Davunetide (AL-108) in Predicted Tauopathies - Pilot Study

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