Olink panels overlap, D&D Phamatech (NLY01 NCT04154072), DBS (EARLYSTIM Schuepbach 2013 + Indication / Side effects / Prognosis bullets), DDC (Aromatic L-amino acid decarboxylase): AADC enzyme / Keaton 2023 / Perera 2023 / Petlawski 2023 / Cieselska 2017 / 18F-L-DOPA PET (Calabria 2016), Diagnosis of PD (MDS criteria / Postuma 2017 / Geils’s criteria opener)

D&D Phamatech

• Neuraly (D&D Phamatech)‘s NLY01, is in a p2 clinical NCT04154072
• 홍유석, 이슬기, 홍성훈

DBS

Clinical trial		DBS	UPDRS III	Best medical practice
Williams a randomised, open-label trial
Weaver, 2009 RCT, Blinded, (H&Y 3.5)	UPDRS III: 0개 백 (0개 → 0)		UPDRS III: table 2, 35% ↓
RCT, Bcca FDA label p28 (Schuepbach, 2013 #1892)	UPDRS III: table 2, 53% ↓		UPDRS III: table 2, 53% ↓	UPDRS III: 4% ↓ ish
It is most effective for people who experience disabling tremors, wearing-off spells and medication-induced dyskinesias, with studies showing benefits lasting at least five years. That said, it is not a cure and it does not slow PD progression. It is also not right for every person with PD. It is not thought to improve speech or swallow issues, thinking problems or gait freezing.

Indication

• At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications.
• You have had PD symptoms for at least five years.
• You have “on/off” fluctuations despite consistent and regular medication dosing.
• You have dyskinesias.
• You are unable to tolerate anti-parkinson’s medications due to side effects.
• You have tremor that is not well controlled with medication (even with medical management by a movement disorders specialist).
• You continue to have a good response to PD medications, especially carbidopa/levodopa, although the duration of response may be insufficient.
• You have tried different combinations of anti-Parkinson’s medications under the supervision of a movement disorders neurologist.
• You have PD symptoms that interfere with daily activities.

Side effects

• There is a one to three percent chance of infection, stroke, cranial bleeding or other complications associated with anesthesia, per side that is done

Prognosis / outcome

• Although most people still need to take medication after undergoing DBS, many people experience considerable reduction of their PD symptoms and can greatly reduce their medications. The amount of reduction varies from person to person.
• The reduction in dose of medication leads to decreased risk of side effects such as dyskinesia (involuntary movements of the arms, legs and head).
• He beneficial effects of deep brain stimulator surgery will last beyond 15 years,” Dr. Michael Okun, national medical advisor to the Parkinson’s Foundation, said DBS, when used with medication, has long-lasting effects in some patients 2021: 6, 7

Resources:

• https://sciencedayparkinsons.com/2019/12/15/dbs/ so good, plain English

DDC

AADC RNA expression — Aromatic L-amino acid decarboxylase

RNA expression	Kidney → small intestine → colon → SN → adrenal gland
(Trex)	AADC is not a rate-limiting enzyme like TH. Although dopaminergic fibers carry the bulk of the AADC, the enzyme is also found in serotonergic fibers as AADC plays a role in serotonin synthesis as well
(Cieselska 2017 #2785) postmortem brain	AADC enzymatic activity in PD (n = 8), greatly reduced across striatum (striatum, caudate, putamen). js: what about cortex? Late stage 가? (도?)
kidney	Dopamine is synthesized within the proximal tubule from circulating L-Dopa via the enzyme L-amino acid decarboxylase [1-3]. There are also renal nerves that contain dopamine, although the physiologic significance of these nerves is unclear.
	The main source of renal dopamine comes from the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) from plasma [4]. L-DOPA is taken up by the renal tubules from circulation or glomerular filtration and is converted to dopamine by aromatic amino acid decarboxylase (AADC) [42-43].
(Keaton, 2023 #2779)	higher probability of PD development among certain CKD individuals, including those who resided in rural areas (aHR, 1.18; 95% CI: 1.10-1.37, p = 0.022). maintained a normal weight (aHR, 1.14, 95% CI: 1.04-1.06, p = 0.060), or had multiple times above background (aHR, 1.05, 95% CI: 1.02-1.10, p = 0.046). Therefore, these clinical or environmental factors may influence the incidence of PD in CKD patients. In conclusion, our results suggest that the general CKD population may not exhibit a greater propensity for PD pain. (Rutledge 2024, PPMI; OLINK SOMASCAN; LC-MS/MS (urine only))
(Perera, 2023) Swedish BioFINDER 1 & 2 cohort, olink
(Petlawski, 2023 #2787) olink, Stockholm cohort, BioFIND cohort
18F-L-DOPA PET ITRC, (Calabria, 2016 #2786)	Compensatory mechanism elsewhere in the brain as a response to nigrostriatal degeneration (Rutledge 2024), in order to provide faster response to the treatment. i: leakage of peripheral DDC into the CSF.

• Baseline level vs UPDRS (datscan) progression
• (i) FDA: 미상실간 이미 액 어떻게? 시기 가 위히 patient recruiting 시 시기 (-?)
• Correlation CSF vs Plasma vs Urine: (Perera, 2023) high correlations between CSF and plasma DDC levels (Spearman p: 0.7, p < 2.2 x 10^-16) in a subsample of 142 BioFINDER 1 participants (LBD: n = 33; atypical PS: n = 56; controls: n = 53), of which 29 were CUs and 24 had SCD.
• (cross-sectional) DDC vs UPDRS

Diagnosis of PD

MDS-PD criteria	International Parkinson and Movement Disorder Society (MDS) task force
		(Postuma, 2017 #1098/이게 경우)
Diagnosis of Clinically Established PD requires: (1) absence of absolute exclusion criteria, (2) at least two supportive criteria, and (3) no red flags Probable PD (1) absence of absolute exclusion criteria (2) presence of red flags counterbalanced by supportive criteria - If one red flag is present then there must also be at least one supportive criterion. - If two red flags, at least two supportive criteria are needed. - No more than two red flags are allowed for this category.
United Kingdom PD Society Brain Bank
Geib's criteria

(Marrub, 2018 #1099)

Stages of early PD	PRECLINICA PD	Prodromal PD	Clinical PD
	neurodegenerative process is started without evident symptoms or signs of the disease	presence of signs of this disease are present, but insufficient to define a full clinical picture of PD	diagnosis of PD is achieved, based on the presence of classical motor signs (according to MDS-PD criteria)