Stephens 1978 (continued), animal model literature rows, Outcome measure in nGD (SST / mSST)

Stephens 1978 (continued)

	2 day post	3 day post	4 day post	5 day post	8 day post	12 day post
	24%	42% / 64%	61%	63%

nothing done to Saposin C

Animal model literature rows

#	Reference / strain	Treatment	Enzyme inhibition (24h post) / substrate	Substrate measured	Clinical / phenotype	Neuropathology
2	Ginns (2014, US) (C57BL/6 mice, males aged 8 weeks)	100mg/kg daily for 9 days in mouse Nothing done to Saposin C	Not shown		1. motor impairments, but no change in food intake or body weight	1. TH+ cell not done 2. microglial activation in SN (IBA1 IF visualized but not quantified) 3. a-syn accumulation in SN & Striatum (IF, not Q) ↓ striatal dopamine release
3	Xu (2008) (post-natal day 5 or 15)	100mg/kg, IP, daily for 6-11 days in mouse Nothing done to Saposin C	4.5% (3hr post injection) → 10.2% of WT (24hr post injection)		Die by the age of 14 days	↓ microglial activation 노력 애기 못 잔겠음. (1 CD68 cells, no Q) 2. Neuronal loss ↑ TUNEL cells, no Q (↓ NeuN Ab cells, Q) Indeed, the TG model was mimicked by CBE by treatment for 10-14 days with complete recapitulation of the CNS abnormalities. here it was highly specific and provides a reliable and informative phenotype.
4	Vitner (2014) (C57BL/6 mice, aged from 8 days)	50mg/kg (or PBS) IP, daily Nothing done to Saposin C				RIPK3 in cell death
5	Manning-Bog (2009) (C57BL/6 mice, 3 weeks)	A single 200mg/kg, ip, Nothing done to Saposin C	Not done	Not done 48 h post CBE injection		1. a-syn ↑ in SN but not in cortex / hippocampus (IF, not Q) 2. ↑ a-syn (WB) in ventral mesencephalon homogenates: monomer 가 particulate fraction (insoluble 과 debris 가 같이 있겠구만)에서 증가 (by 20%), supernatant fraction (=내 normal lysate, cellular debris 등만 제거된 상태이니, cytosolic 과 membrane form 이 같이있겠구만)에서는 안 증가, (oligomer 는 양 fraction 에서 안 보임) GFAP in SN & cortex (IF, not Q)
6	Rockenstein (2016 #594) / Genzyme poster / Panarello, 2013 WT mice & PrP-A53T-SNCA mice	100mg/kg, 3x/week, 10 w Nothing done to Saposin C,	Not done	Not done	5-panel chart labels: A GCase Activity, B Hexosaminidase Activity, C GlcCer, D GlcSph, E α-Synuclein ELISA. Groups: WT, PrP-A53T-SNCA × Saline / CBE.
7	Rocha (2015) Male BDF1 mice 3-4 months	100mg/kg, IP, daily for 28 days	Inhibition (post 24h): 자로잼 Forebrain: 29.1% Midbrain: 20.8% Cbll: 24.4% Recovery (post 7d): Forebrain: 77.9% Midbrain: 80.2% Cbll: 78.1%	Substrate measured	1. No change in the number of dopaminergic (TH + NeuN-labeled) neurons in SNpc or the number of NeuN-labeled neurons in the pars reticulate, also no effect on dopaminergic striatal fiber density 2. Iba-1-positive microglia throughout the brain, which remains highly reactive even 7 days postcessation of CBE, (ie cortical layer V, striatum and SN), not quantified but just by IF 3. ↑ proteinase-K resistant a-syn aggregates (by IHC) 1. ↑ LC3II (by 36%, 자로잼), ↑ LAMP2 (51% 자로잼), p62: (only trend due to high error bar despite 71.4% increase), ↑ Cathepsin D (which normaly degrades a-syn) 2. neuronal cell loss in the motor and somatosensory cortices.
	Kanfer (1975) (C57BL/6 mice, aged from 3 months)	100mg/kg, IP, daily for 3 weeks				5 fold increase in brain

Outcome measure in nGD

Tool	Reference	Range		Examples used
SST (severity scoring tool) (Original)	(Davies, 2007 #828)	Normal 0 - worst (total) 39
mSST (Modified Severity Scoring Tool)	(Davies, 2011 #552)	Normal 0 - worst (total) 36, 12 domains		Venglustat P2 "LEAP"

mSST domain scoring

Domain	Description	Score
Gaze palsy	Normal (although not likely in diagnosis)	0
	Horizontal saccades absent, vertical saccades present	0.5
	Horizontal saccades and vertical saccades absent	1
Ophthalmology	Normal	0
	Cranial nerve palsy (previously corrected or not)	1
	Cranial nerve palsy (reappearing despite surgical correction)	2
Epilepsy	No seizures.	0
	Seizures not requiring anticonvulsants	3
	Seizures controlled with anticonvulsants.	4
	Seizures requiring combination therapy or resistant to anticonvulsants	5
Age at first seizure	Younger than 5 years	3
	5-10 years	2
	10-15 years	1
	16 years or over, or seizure free	0
Development / Cognitive ability	Normal	0
	Mildly impaired (IQ less than 85 or equivalent)	1
	Moderate (IQ 50-57 or equivalent)	2
	Severe (more than half their chronological age)	3
Ataxia of gait	Normal, apparent only on tandem walking	0
	Ataxia on straight gait, able to walk without assistance	1
	Able to walk only with assistance	2
	Unable to walk	3
Cerebellar tremor	No intention tremor	0
	Intention tremor not affecting function	0.5
	Intention tremor with marked impact on function	2
Pyramidal	Normal tone with increased reflexes	0
	Mildly to moderately increased tone and reflexes	2
	Increased tone and reflexes with clonus, whether unsustained or sustained	3
	Severe spasticity with inability to walk	5
Extrapyramidal	Normal	0
	Variable tone and posturing not impairing function, with or without therapy.	1
	Variable tone and posturing impairing function, despite therapy	2
	Significant rigidity with no/minimal benefit from therapy	3
Swallowing difficulties / Oral bulbar function	Normal	0
	Mild dysphagia (excess drooling)	1
	Moderate dysphagia (risk of aspiration, modification to diet required)	2
	Severe dysphagia (requiring non-oral feeding)	3
Speech	Normal (and those too young yet to speak)	0
	Mild to moderate dysarthria impairing intelligibility to unfamiliar listener	1
	Severe dysarthria with most speech unintelligible to familiar and unfamiliar listener	2
	Anarthria	3
Spinal alignment	Normal	0
	Mild kyphosis - but flexible and not requiring bracing	1
	Moderate kyphosis - partially corrected by bracing	2
	Severe kyphosis - not corrected by bracing or requiring surgery	3
Total		36

Uncertain Spans

location	transcription	uncertainty
Stephens 1978 tail	full row-by-column alignment for 2-12 day post rows	not all column cells are clearly visible at the top of frame; values transcribed where legible.
mSST scoring / Cognitive ability	Moderate (IQ 50-57 or equivalent)	reads as written; the IQ range is small, OCR also returned IQ 50-67.