20240722_184354

Reduced iNOS, TNFα, and IL1β, ↓ LID

Below table from (Biglan, 2017 #1563)

Table 1. Representative Phase III disease-modifying trials in Parkinson disease.

Trial	Intervention	N	Design	PD population	Duration	Primary outcome(s)	Results
DATATOP	Deprenyl and centertocopherol	800	2 × 2 factorial	Early untreated	24 months	Time to development of disability requiring levodopa therapy	Deprenyl resulted in reduced hazard of requiring levodopa therapy
PRECEPT	CEP-1347 10 mg BID 25 mg BID 50 mg BID	806	Parallel group	Early untreated	24 months	Time to development of disability requiring dopaminergic therapy	Terminated early for futility
QE3	Coenzyme Q10 1200 mg/day 2400 mg/day	600	Parallel group	Early untreated	16 months	UPDRS change	Terminated for prespecified futility
ADAGIO	Rasagiline 1 mg/day 2 mg/day	1176	Delayed start	Early untreated	18 months	1) Superiority of UPDRS change in early start to placebo between weeks 12-36 2) Superiority of UPDRS change in early start to delayed start between baseline and week 72 3) Noninferiority of early to delayed start in rate of UPDRS change between weeks 48-72	1 mg/day but not 2 mg/day met all criteria for efficacy
LS1	Creatine	1741	Parallel group	Early stable treatment	60 months	Global statistical test defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity (UPDRS)	Terminated due to futility in an interim analysis of 955 subjects followed up for 5 years

MoA	Product name	RoA	Compound Phase in Indication	Company Name	Trial Source Online	US	EU	JPN	RoW	Est. Launch (US)
Targeting α-Syn	Prasinezumab	Injection (IV)	Phase II	Roche/ Prothena	NCT03100149	I	I			Q3 20...
Targeting α-Syn	BIIB-054	Injection (IV)	Phase II	Biogen	NCT03318523	I	I		I	Q4 20...
Targeting α-Syn	TAK-341	Injection	Phase I	takeda						2027+
Targeting α-Syn	Lu AF82422	Injection (IV)	Phase I	Lundbeck	NCT03611569	I				2027+
Targeting α-Syn	ABBV-0805	Injection (IV)	Phase I	AbbVie /BioArctic	NCT04127695	I				2027+
Targeting α-Syn	UB-312	Injection (IM)	Phase I	United Neurosciences	NCT04075318		I			2027+
Targeting α-Syn	UCB0599	Oral	Phase I	UCB/Neuropore	n/a					2027+
GBA Pathway	Venglustat	Oral	Phase II	Sanofi (Genzyme)	NCT02906020	I	I	I	I	Q2 2025
GBA Pathway	LTI-291 (BIA 28-6156)	Oral	Phase II	Lysosomal	NTR7299		I			EU: Q1 2026
GBA Pathway	PR001	Intracisternal	Phase I/II	Prevail	NCT04127578	I				2027+
Targeting LRRK2	DNL-201	Oral	Phase II	Denali	NCT03710707	I				Q1 2025
Targeting LRRK2	DNL-151	Oral	Phase I	Denali	NCT04056689		I			EU: Q2 2024
Targeting LRRK2	BIIB-094	Intrathecal	Phase I	Biogen / Ionis	NCT03976349	I				2027+
Neuronal Survival	EPI-589	Oral	Phase II	Sumitomo/ BioElectron	NCT02462603	I	I			Q2 2022
Neuronal Survival	DA-9805	Oral	Phase II	Dong-A Socio	NCT03189563	I				Q3 2022
Neuronal Survival	Deferiprone DR	Oral	Phase II	ApoPharma	NCT02728843		I		I	EU: Q1 2024
Others	Tasigna (Nilotinib)	Oral	Phase II	Novartis/ Michael J Fox Found.	NCT03205488	I				Q1 2022
Others	K0706	Oral	Phase II	SPARC (Sun Pharma)	NCT03655236	I				Q2 2024

addition,
(Vrasidlo et al., 2016).

Mechanism of action	Agent	Sponsor/Partner	Phase	N	Study population	Dose	Duration	Primary outcome	Result	Ref.
Active α-syn immunization	PD01A (C-terminal epitope of human α-syn)	Affiris AG	I	32	45–65 years, diagnosis < 4 years, stable dose of PD meds	15 µg or 75 µg every 4 weeks × 4; 15 µg or 75 µg booster no. 1; 75 µg booster no. 2	52 weeks, followed by 39 weeks follow-up; 24 weeks after booster no. 1; 52 weeks after booster no. 2	Safety and tolerability	Safe and well tolerated, positive humoral immune response	NCT01568099, NCT01885494, NCT02216188, NCT02618941 [15]
Passive α-syn immunization	PRX002/RG7935/ Prasinezumab (PASADENA)	Roche/Prothena	II	316	40–80 years, diagnosis < 2 years, PD DaTscan, no DA rx (stable MAOB-I allowed)	1500 mg or 4500 mg vs placebo every 4 weeks × 52 weeks	52 weeks	ΔMDS-UPDRS I-III at week 52	Negative; positive significant motor outcomes	NCT03100149 [16]
	BIIB054 (SPARK)	Biogen/PSG	II	357	40–80 years, diagnosis < 3 years, PD DaTscan, no PD meds	250 mg, 1250 mg, 3500 mg vs placebo every 4 weeks × 52 weeks	52 weeks with follow-up to 72 weeks and 178 weeks	ΔMDS-UPDRS I-III at weeks 52 and 72	Active, not recruiting; estimated completion 6/2021	NCT03318523 [17]
	Lu AF82422	Lundbeck	I	84	40–80 years, stable dose × 3 months	Single ascending dose	12 weeks	Safety and tolerability	Recruiting; estimated completion 12/2020	NCT03611569 [18]
	MEDI-1341	AstraZeneca	I	48	Healthy volunteers	Single ascending dose	13 weeks	Safety and tolerability	Estimated completion 1/2021	NCT03727165
Urate elevation/antioxidant	Inosine (SURE-PD3)	NINDS/PSG/MJFF	III	298	> 30 years, diagnosis < 3 years, PD DaTscan, no serum urate level 7.1–	Up to 3 g/day, titrated to ...	24 months	ΔMDS-UPDRS I-III at month 24	Negative, early termination	NCT02642393 [18]

Uncertain Spans

location	transcription	uncertainty
MoA pipeline table launch column	2027+ and quarter values like Q3 20...	The right-most “Est. Launch (US)” column is partially cut at the right edge of the source crop; quarter-year values are read where visible and 2027+ is preserved as printed for the truncated entries.
PD01A reference cell	NCT01568099, NCT01885494, NCT02216188, NCT02618941 [15]	The reference cell stacks four NCT identifiers and one bracketed citation [15]; numeric tokens are read from the source.
Inosine SURE-PD3 dose cell	Up to 3 g/day, titrated to ...	The dose-cell trailing text is partly cropped at the right edge; preserved with an ellipsis.