Study characteristics
Study type
Clinical studies
RCT
Prospective cohort
Case series
Non-randomized prospective comparative
Retrospective comparative
Animal studies
Comparative animal study
Non-comparative animal study
Disease context
Alzheimer's Disease
MS
Other specific neurodegenerative disease
Non-degenerative neuro condition (anxiety, depression, autism, etc)
Unspecified neurodegeneration
Brain injury
Non-neurological context (safety only)
Interventions
FLAP inhibitors
BPP-1001 (MK-591)
MK-886
Other/unspecified FLAP inhibitor
Potential FLAP inhibitor (unknown mech of action)
MK-886 + Sham
MK-88g + FPI
3mg/kg MK-866 ip, Swiss mice
10 mg/kg MK-866 ip, Swiss mice
250 MK866 icv, Swiss mice
500 MK866 icv, Swiss mice
3mg/kg MK-866 ip, C57 mice
Vehicle ip, C57 mice < FLAP inhibitors
10 mg/kg MK-866 ip, C57 mice
12-mo old 10mg/kg ip MK-886 Swiss mice
MK-886 + MPTP
one dose, ip 3mg/kg MK-886, mice
one dose, ip 10mg/kg MK-886, mice
6 dose MK-886, mice
6 dose MK-886, 5-lox-ko mice
long-term MK-886, mice
Acetylbiswellic acid
0.3 mg/kg iv MK-886
2 mg/kg iv MK-886
3 mg/kg iv MK-801
MK-591, 7days post TBI
MK-591, 30days post TBI
MK-591 12.5 mg, humans
MK-591 50 mg, humans
MK-591 100 mg, humans
MK866 + Cuprizone
Comparators
Sham/placebo/vehicle
Other leukotriene pathway inhibitor
Other comparator
Vehicle + Sham
Vehicle + FPI
Vehicle ip, Swiss mice
vehicle icv, Swiss mice
Zileuton po
Vehicle po
Vehicle ip, C57 mice < Comparators
12-mo old Vehicle ip MK-886 Swiss mice
MPTP
Boscari
Sham
Control (w/TBI)
5-LOX-KO + MK-886
5-LOX-KO + Vehicle
Vehicle, one dose, mice
6 dose vehicle, 5-lox-KO mice
long-term vehicle, mice
6-dose vehicle, mice
Vehicle iv
SCH 58261 0.01 mg/kg iv
Control, 7days post TBI
Placebo, humans
Cuprizone
Patient Characteristics
Sex
Species
Mouse
Rabbit
Guinea pig
Rat
Non-human primate
Human
Age group
Young (pre-adult)
Old
No age selection
Adult
Treatment characteristics
FLAP inhibitor dose regimen
Outcomes
Function
Memory and learning test
Fear conditioning score (median, IQR)
Fear conditioning context, AD mice
Fear conditioning cued, AD mice
Water maze arm entries (mean, SD)
Water maze arm alternations (%)
Water maze contextual fear response (%freezing)
Water maze cued fear response (%freezing)
Y-maze
Y-maze arm entries, AD mice
Y-maze alternations, AD mice
Water Maze, learning task
RAWD water maze, errors, TBI rats
RAWD water maze, perseverance, TBI rats
RAWD water maze, reversal errors, TBI rats
Reflex test
Motor test
Rotarod time (mean, SD)
Modified Garcia Score, SAH rats
Other function measures
Forced swim test time (mean, SD)
fEPSPs
fEPSPs amplitude 0-10 min post tetanus, AD mice
fEPSPs amplitude 170-180 min post tetanus, AD mice
Pair-pulse ratio
Paired pulse ratio, impulse interval = 20, AD mice
Paired pulse ratio, impulse interval = 50, AD mice
Paired pulse ratio, impulse interval = 100, AD mice
Paired pulse ratio, impulse interval = 200, AD mice
Paired pulse ratio, impulse interval = 1000, AD mice
Long-term potentiation
LTP, TBI Rats
Forced Swim test
Basic movements, one-dose, mice
Climbing, one dose, mice
Rest time, one dose, mice
Basic movements, 6 doses, mice
Climbing, 6 doses, mice
Rest time, 6 doses, mice
Basic movements, long-term (2wk) dosage, mice
climbing, long-term (2wk) dosage, mice
rest time, long-term dosage (2wks), mice
Basic movements, long-term (3wk) dosage, mice
climbing, long-term (3wk) dosage, mice
rest time, long-term dosage (3wks), mice
Gross motor dysfunction
72h gross motor dysfunction, TBI rats
1wk gross motor dysfunction, TBI rats
10day gross motor dysfunction, TBI rats
Water Maze, perseverence
Anxiety
Elevated plus maze
Open-arm entries, mice
Open-arm time, mice
Closed-arm entries, mice
Closed-arm time, mice
dark-light box
Time in bright side, mice
Time in dark side, mice
transitions, mice
Tissue metrics
Microglia infiltration
Lectin staining (microglia infiltration)
CD43+ cell count
CD43 cells (IHC), parietal cortex 24-h post TBI Rats
CD43 cells (IHC), CA3 24-h post TBI Rats
CD43 cells (IHC), dentate gyrus 24-h post TBI Rats
CD43 cells (IHC), vis/aud cortex 24-h post TBI Rats
CD43 cells (IHC), parietal cortex 72-h post TBI Rats
CD43 cells (IHC), CA3 72-h post TBI Rats
CD43 cells (IHC), dentate gyrus 72-h post TBI Rats
CD43 cells (IHC), vis/aud cortex 72-h post TBI Rats
CD68+ cell count
CD68 cells (IHC), parietal cortex 24-h post TBI Rats
CD68 cells (IHC), CA3 24-h post TBI Rats
CD68 cells (IHC), dentate gyrus 24-h post TBI Rats
CD68 cells (IHC), vis/aud cortex 24-h post TBI Rats
CD68 cells (IHC), parietal cortex 72-h post TBI Rats
CD68 cells (IHC), CA3 72-h post TBI Rats
CD68 cells (IHC), dentate gyrus 72-h post TBI Rats
CD68 cells (IHC), vis/aud cortex 72-h post TBI Rats
CD11b mRNA (microglia)
CD11b mRNA, MS mice brain homogenate
CD11b+ cell count (microglia)
CD11b cells, corpus callosum, MS mice
CD11b cells, cortex, MS mice
IBA-1 staining (pixel positivity index)
Iba-1, cortex, TBI mice
Iba-1, corpus callosum, TBI mice
Iba-1, dentate gyrus, TBI mice
CD45 protein < Microglia infiltration
CD45 protein (Western blot), brain homogenate, AD mice
CD45 (IHC), brain cortex, AD mice
CD45 (IHC), AD mouse cortex
CD45 (IHC), AD mouse brain homogenate
Cell death
NeuN neuronal loss
Tissue inflammatory markers
tissue IL-1B (pg/mg)
tissue IL-1B mRNA
IL-1beta mRNA, MS brain homogenate
tissue TNFa mRNA
TNFalpha mRNA, MS brain homogenate
tissue IL-6 mRNA
IL-6 mRNA, MS brain homogenate
tissue IL-6 protein (pg/mg)
IL-6 protein, MS mice forebrain
Tissue IL-1beta
IL-1beta protein (ELISA), AD mice brain homogenate
COX-2 cells
COX-2 cells (IHC), parietal cortex 24-h post TBI Rats
COX-2 cells (IHC), CA3 24-h post TBI Rats
COX-2 cells (IHC), dentate gyrus 24-h post TBI Rats
COX-2 cells (IHC), vis/aud cortex 24-h post TBI Rats
COX-2 cells (IHC), parietal cortex 72-h post TBI Rats
COX-2 cells (IHC), CA3 72-h post TBI Rats
COX-2 cells (IHC), dentate gyrus 72-h post TBI Rats
COX-2 cells (IHC), vis/aud cortex 72-h post TBI Rats
Edema/swelling
Brain water content (BWC, %)
Brain swelling (BS, %)
Normalized brain swelling, TBI Rats
Intracranial pressure
ICP, 24-h post TBI, rats
ICP, 72-h post TBI, rats
Edema (MRI, %)
Edema (MRI, pixel intensity)
Gross pathology
Lesion size (MRI)
Sum of CNS lesion score
infarct volume- histology
Lesion volume
Lesion volume, 24h-post TBI rat T2 (median)
Lesion volume, 72h-post TBI rat T2 (median)
Lesion volume, 72h-post TBI rat T2 (mean)
CNS sum score of lesions
Histo, CNS sum score of lesions, guinea pics immunized with encephalitogenic mix
Ischemic volume
Ischemic Volume, total, rats, occlusion
Ischemic Volume, cortical, rats, occlusion
Ischemic Volume, striatal, rats, occlusion
Blood-brain barrier disruption
EB-positive cell count
CA1-EB+ cells, TBI Rats
CA2-EB+ cells, TBI Rats
CA3-EB+ cells, TBI Rats
Extravasation of EB
measures of reactive astrocytosis
GFAP (astrocyte marker), protein
GFAP (Western blot), AD mice, % control, cortex
GFAP (Western Blot), AD mice, % control, Corpus callosum
GFAP (western blot), AD mice, % control, dentate gyrus
GFAP (IHC), AD mouse cortex
GFAP mRNA (astrocyte marker)
GFAP after cuprizone, AD mice, fold difference, cortex
GFAP (IHC)
GFAP (IHC), cortex, mice
GFAP (IHC), corpus callosum, mice
GFAP (IHC), dentate gyrus, mice
Tissue leukotrienes
Tissue LTC4 (pg/100 ul)
Tissue LTC4 (pg/mg)
LTC4 (HPLC), ipsilateral hemisphere, TBI rats
LTC4 (HPLC), contralateral hemisphere, TBI rats
LTC4 (HPLC), ipsilateral cortex, TBI rats
LTC4 (HPLC), ipsilateral hippocampus, TBI rats
LTC4 protein, ipsilateral pg/mg, rat
LTC4 protein, contralateral pg/mg, rat
Cysteinyl LT levels (fmol/g tissue)
Cysteinyl LT levels (fmol/g tissue), rat cortex, brain ischemia
Tissue LTB4 (ng/L protein)
LTB4 protein, SAH Rat, ng/L
LBT4, striata of PD mice % control
LBT4, subst niagra of PD mice % control
Tissue LXA4
kainic-acid-induced tissue LXA4, hippocampus (ELISA)
LTB4 pg/mL
LTB4, RIA, Guinea pigs
LCT4 pg/mL
LCT4, RIA, Guinea pigs
Other tissue metrics
PSD-95 levels
PSD-95, western blot (AD mouse-brain homogenate)
PSD-95, IHC (AD mouse cortex)
PSD-95 protein (IHC), brain homogenate, AD mice
SYP levels
myelin basic protein (MBP) mRNA
MBP mRNA, MS mice brain homogenate
Tissue 5-LO mRNA
Tissue 5-LO protein levels
5-lipoxygenase protein (west blot), AD mice brain homogenate
MAP-2 levels
MAP-2, western blot (AD mouse-brain homogenate)
MAP-2, IHC (AD mouse cortex)
MAP-2 protein (IHC), brain homogenate, AD mice
APP
APP Protein, optic density (AD mouse-brain homogenate)
APP+ neurons, MS mice
pGSK-3alpha
pGSK-3alpha, western blot (AD mouse-brain homogenate)
pGSK-3beta
pGSK-3beta, western blot (AD mouse-brain homogenate)
Synaptophysin
Synaptophysin, western blot (AD mouse-brain homogenate)
Synaptophysin, IHC (AD mouse cortex)
Synaptophysin, (IHC) brain homogenate, AD mice
GSK-3beta kinase activity
GSK-3beta kinase activity, western blot (AD mouse-brain homogenate)
PS-1 protein
PS-1 Protein (western blot), brain homogenate, AD mice
PS-1 mRNA (PCR), AD mice, brain homogenate
Nicastrin protein
Nicastrin Protein (western blot), brain homogenate, AD mice
nicastrin mRNA (PCR), AD mice, brain homogenate
Nicastrin Protein (western blot), brain homogenate, AD mice (OD)
Pen-2 Protein
Pen-2 Protein (western blot), brain homogenate, AD mice
Pen-2 mRNA (PCR), AD mice, brain homogenate
anterior pharynx defective-1 Protein
anterior pharynx defectiv-1 Protein (Western blot), brain homogenate, AD mice
anterior pharynx defective-1 mRNA (PCR), AD mice, brain homogenate
CTF-alpha Protein
CTF-alpha Protein (western blot), brain homogenate, AD mice
CTF-Beta Protein
CTF-beta Protein (western blot), brain homogenate, AD mice
cdk5 Protein
cdk5 Protein (Western blot), brain homogenate, AD mice
p35 Protein
p35 Protein (western blot), brain homogenate, AD mice
p25 Protein
p25 Protein (western blot), brain homogenate, AD mice
JNK Protein
JNK protein (Western blot), brain homogenate, AD mice
SAPK/JNK protein
SAPK/JNK protein (Western blot), brain homogenate, AD mice
CD45 protein < Other tissue metrics
Beta-secretase
beta-secretase protein (Western blot), AD mice, brain homogenate
beta-secretase mRNA (PCR), AD mice, brain homogenate
beta-secretase protein (Western blot), AD mice, brain homogenate (OD)
CREB
CREB protein (western blot), AD mouse brain homogenate
p-CREB protein (western blot), AD mouse brain homogenate
Sp1
SP-1 protein (western blot), AD mouse brain homogenate
alpha-SMA
alpha-SMA protein (western blot), SAH rat brain
Smemb
Smemb protein, western blot, SAH rat brain
PPAR-alpha
PPAR-alpha protein (Western blot), mouse brain homogenate
apoE
apoE protein (Western blot) mouse brain homogenate
lipoprotein receptor-related protein-1
lipoprotein receptor-related protein 1 (western blot) mouse brain homogenate
cerebral amyloid angiopathy severity
cerebral amyloid angiopathy, mouse cortex
cerebral amyloid angiopathy, mouse hippocampus
Plaque load
Plaque load, mouse cortex
Plaque load, mouse hippocampus
TH+ neurons
TH+ neurons after MPTP, PD mice
Dopamine levels
Dopamine levels in striata of PD mice after MPTP
DOPAC levels
DOPAC levels in striata of PD mice after MPTP
HVA levels
HVA levels in striata of PD mice after MPTP
Neuronal density
Neuronal density 1, TBI rat cortex
Neuronal density 2, TBI rat cortex
Iba-1
myelin score
myelin score, MS mice corpus callosum
myelin score, MS mice cortex
Tau protein metrics
Tau protein levels
Western Blot, tau, Cortex homogenate
Tau protein WB (% control), AD mice
Insoluble tau WB (% control), AD mice
Immunohistochemistry, tau, hippocampus
Tau protein IHC (% control), AD mice
Insoluble tau IHC (% control), AD mice
phosphorylated tau
Western Blot, phosphorylated tau, Cortex homogenate
Tau Ser396 WB (% control), AD mice
Tau Ser396 WB (abs value), AD mice
Tau Ser396/Ser404 WB (abs value), AD mice
Tau Ser396/Ser404 WB (% ctrl), AD mice
Tau Thr231/Ser235 WB (abs value), AD mice
Tau Thr231/Ser235 WB (% Control), AD mice
Total phosphorylated tau (HT7) WB (% Control), AD mice
Immunohistochemistry, phosphorylated tau, hippocampus
Tau Thr231/Ser235 IHC (% Control, phosphorylated/total tau), AD mice
Tau Ser396 IHC (% Control, phosphorylated/total tau), AD mice
Tau Ser396/Ser404 IHC (% Control, phosphorylated/total tau), AD mice
Amyloid beta metrics
insoluble ABeta levels
soluble ABeta levels
Amyloid Beta 1-40, immunoprecip RIPA extracted, mouse cortex (pmol/mg), AD mice
Amyloid Beta 1-40, immunoprecip FA extracted, mouse cortex (pmol/mg), AD mice
Amyloid Beta 1-42, immunoprecip RIPA extracted, mouse cortex (pmol/mg), AD mice
Amyloid Beta 1-42, immunoprecip FA extracted, AD mouse cortex (pmol/mg)
Amyloid Beta, IHC, AD mouse brain (% Control)
Amyloid Beta 1-40, immunoprecip RIPA extracted, AD mouse hippocampus (pg/mg)
Amyloid Beta 1-40, immunoprecip FA extracted, AD mouse hippocampus (pg/mg)
Amyloid Beta 1-42, immunoprecip RIPA extracted, AD mouse hippocampus (pg/mg)
Amyloid Beta 1-42, immunoprecip FA extracted, AD mouse hippocampus (pg/mg)
Amyloid Beta 1-40, immunoprecip RIPA extracted, AD mouse cortex (pg/mg)
Amyloid Beta 1-40, immunoprecip FA extracted, AD mouse cortex (pg/mg)
Amyloid Beta 1-42, immunoprecip RIPA extracted, AD mouse cortex (pg/mg)
Amyloid Beta 1-42, immunoprecip FA extracted, AD mouse cortex (pg/mg)
Amyloid Beta, ELISA, AD mouse brain (% Brain)
GPR17
GPR17 mRNA, MS mice
Blood tests
Blood inflammatory markers
Blood leukotrienes
Plasma Leukotriene B4 (LTB4, pg/ml)
Plasma Leukotriene C4 (LTC4, pg/mL)
Other blood tests
Plasma UCH-L1 (pg/mL)
Plasma GFAP (ng/mL)
Plasma Lipoxin A4 (LXA4, ng/mL)
Plasma LXA4 induced by kainic acid, mice (ELISA)
Safety events
Mortality
Decline in overall health
Organ pathology
Body weight
Bodyweight, pre-TBI, rats
Bodyweight, 24h-post TBI, rats
Bodyweight, 72h-post TBI, rats
Clinical symptoms
Ataxia
Paresis
Paralysis
Survival at day 21
Adverse events leading to withdraw
Lack of response
decreased hematocrit
abdominal pain/diarrhea
malignant neoplasm of brain
worsened UC
Rash