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The PD Node

The Parkinson’s Disease Node conducts cutting-edge translational and clinical research with the aim to improve the diagnosis, treatment, and quality of life of individuals with PD and other parkinsonisms, including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS).

Node leader: Charalampos Tzoulis

Charalampos Tzoulis, MD, PhD, is professor of neurology and neurogenetics at the University of Bergen and Haukeland University Hospital, Bergen, Norway. He is also Co-Director of the Neuro-SysMed, and Director of the DECODE-PD, KG Jebsen Centre for Translational Research in Parkinson’s disease. An internationally recognised expert in movement disorders and neurodegeneration, Prof. Tzoulis has made significant scientific contributions, particularly in understanding mitochondrial dysfunction and NAD metabolism in PD. 

The PD Node is globally acknowledged for implementing full-cycle translation – from the laboratory to the bedside and back – and for being a world leader in NAD-replenishment therapy for neurodegeneration. The Node’s work has constituted the foundation for multiple clinical trials across neurodegenerative diseases at the Centre and across the globe. 

Node activities  

Basic and translational research at the PD Node has nominated mitochondrial function and NAD-metabolism as promising therapeutic targets primarily for PD and, by extension, other neurodegenerative and neuroinflammatory disorders, including Alzheimer’s disease, ALS, and MS. Inspired by these findings, the PD Node conducts multiple clinical trials of NAD-replenishment therapy, with a broad range of objectives ranging from establishing safety and pharmacokinetic profiles, to determining the optimal biological dose for brain diseases, and testing efficacy in delaying or preventing PD and other parkinsonisms. Moreover, this research has catalysed several other NAD-replenishment trials at the Centre, targeting Alzheimer’s disease, ALS, and MS (see respective sections).

In addition, the PD Node is working actively on setting the foundations for individualised medicine in PD, by running an international initiative aiming to stratify PD according to underlying molecular mechanisms and develop biomarkers for patient selection for tailored therapies. Notably, in 2024, they published groundbreaking results identifying for the first time a subtype of PD characterised by severe and widespread mitochondrial dysfunction. To enable tailored treatment, they run world-class translational research aiming to identify novel therapeutic targets and candidate therapies for PD and emerging subtypes thereof. 

Furthermore, the PD Node leads and is currently establishing a multiarm multistage (MAMS) platform trial for PD – one of five initiatives in the world – as well as the first ever globally trial accelerator and derisking platform designed to assess target penetration and engagement of promising treatments for PD. 

Investigator-initiated clinical trials: 

During 2024, the PD Node made key advances in their clinical research projects, which include nine clinical trials, and two prospective cohort studies:  

  • The N-DOSE study is a phase II randomised, double blinded dose-optimisation trial of NR in PD. The primary objective is to determine the optimal biological dose of NR for PD and other brain diseases. The study will be completed in 2025. 

  • The NADbrain study is a phase I pharmacokinetic study, aiming to assess the blood and brain NAD-kinetics following the consumption of different NAD-precursors. Based on the results of NADbrain, the optimal dosing frequency of NAD replenishment therapy will be determined. The study was completed in 2024 and the results submitted for publication.

  • The NOPARK study is a phase-III randomised, double-blind, multicentre clinical trial, with the primary objective to assess the efficacy of NR as a neuroprotective therapy, delaying the rate of neurodegeneration and clinical disease progression in PD. The study will be completed in 2025.

  • The NO-PARK extension study is a phase-III open-label, multicentre clinical trial, with the primary objective of assessing the long-term safety of NR therapy in PD. The study will be completed in 2025. 

  • The NADAPT study is a phase-II randomised, double-blind, multicentre trial, aiming to assess the efficacy of NR as a neuroprotective, disease-modifying therapy for atypical parkinsonism, including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). 

  • SLEIPNIR is the world’s first clinical trial accelerator and derisking platform for PD. A multiarm platform designed to assess whether promising disease-modifying therapies engage their intended targets in the human brain, to decide whether they should enter efficacy testing. The platform was developed in 2024 and will start in 2025.

  • HYDRA aims to revolutionise PD trials through an adaptive, multi-arm, multi-stage (MAMS) platform efficacy trial. This innovative approach simultaneously evaluates multiple potential disease-modifying treatments against a single placebo, with the flexibility to discontinue ineffective treatments and reallocate participants to more promising interventions. 

  • NADream is a randomised double-blind trial to explore the effects of NAD-augmentation therapy on human sleep physiology.

  • NOR-RBD is a longitudinal cohort and clinical trial platform for prodromal α-synucleinopathies, identified by REM-sleep behaviour disorder (RBD).

  • NADage is a phase II randomised, double blinded trial of NAD-augmentation with NR in aging-related frailty.

  • The STRAT-PARK initiative is a longitudinal population-based multicentre cohort study aiming to identify biological subtypes of PD and to develop biomarkers enabling patient stratification in clinical practice.

Industry-sponsored clinical trial: 

  • The REASON study, led by Biogen: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB094 in Adults With Parkinson's Disease.

Selected publications from 2024:

  • Nido GS, Castelli M, Mostafavi S, Rubiolo A, Shadad O, Alves G, Tysnes OB, Dölle C, Tzoulis C. Single-nucleus transcriptomics reveals disease- and pathology-specific signatures in α-synucleinopathies. Brain. 2024 Nov 15:awae355. doi: 10.1093/brain/awae355. Online ahead of print. PMID: 39546628.
  • Dick F, Johanson GAS, Tysnes OB, Alves G, Dölle C, Tzoulis C. Brain Proteome Profiling Reveals Common and Divergent Signatures in Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy. Mol Neurobiol. Epub 2024 Aug 21. doi: 10.1007/s12035-024-04422-y. PMID: 39164482. 
  • Flønes IH, Toker L, Sandnes DA, Castelli M, Mostafavi S, Lura N, Shadad O, Fernandez-Vizarra E, Painous C, Pérez-Soriano A, Compta Y, Molina-Porcel L, Alves G, Tysnes OB, Dölle C, Nido GS, Tzoulis C. Mitochondrial complex I deficiency stratifies idiopathic Parkinson's disease. Nat Commun. 2024 Apr 29;15(1):3631. doi: 10.1038/s41467-024-47867-4.PMID: 38684731. 
  • Stige KE, Kverneng SU, Sharma S, Skeie GO, Sheard E, Søgnen M, Geijerstam SA, Vetås T, Wahlvåg AG, Berven H, Buch S, Reese D, Babiker D, Mahdi Y, Wade T, Miranda GP, Ganguly J, Tamilselvam YK, Chai JR, Bansal S, Aur D, Soltani S, Adams S, Dölle C, Dick F, Berntsen EM, Grüner R, Brekke N, Riemer F, Goa PE, Haugarvoll K, Haacke EM, Jog M, Tzoulis C. The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease. Prog Neurobiol. 2024 May;236:102603. doi: 10.1016/j.pneurobio.2024.102603. PMID: 38604582. 
  • Hong Y, Zhang Z, Yangzom T, Chen A, Lundberg BC, Fang EF, Siller R, Sullivan GJ, Zeman J, Tzoulis C, Bindoff LA, Liang KX. The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC derived Cortical Organoid of Alpers' Disease. Int J Biol Sci. 2024 Jan 25;20(4):1194-1217. doi: 10.7150/ijbs.91624. eCollection 2024.PMID: 38385069.

Selected publications from 2023:

  1. Flønes IH, Toker L, Sandnes DA, Lura N, Shadad O, Nyland H, Sandnes DA, Fernandez-Vizarra E, Painous C, Pérez-Soriano A, Compta Y, Molina-Porcel L, Alves GW, Tysnes OB, Dölle C, Nido GS, Tzoulis C. Mitochondrial complex I deficiency stratifies idiopathic Parkinson’s disease. Accepted, Nature Communications, Dec 2023.
  2. Berven H, Kverneng S, Sheard E, Søgnen M, Af Geijerstam S, Haugarvoll K, Skeie, GO, Dölle C, Tzoulis C. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease. Nat Commun.
    2023 Nov 28;14(1):7793.
  3. Neufeld LM, Ho E, Obeid R, Tzoulis C, Green M, Huber LG, Stout M, Griffiths JC. Advancing nutrition science to meet evolving global health needs. Eur J Nutr. 2023 Dec;62(Suppl 1):1-16
  4. Gaare JJ, Brügger K, Nido GS, Tzoulis C. DNA methylation age acceleration is not associated with age of onset in Parkinson disease. Mov Disord. 2023 Nov;38(11):2064-2071.
  5. Dick F, Gard J, and Tzoulis C. Neuronal loss drives differentially expressed protein-pathways in the PSP globus pallidus. Clin Transl Med. 2023 Jul;13(7):e1280.
  6. Toker L, Nido GS, and Tzoulis C. Not every estimate counts. Genome Med. 2023 Jun 7;15(1):41.
  7. Gaare JJ, Dölle C, Brakedal B, Brügger K, Haugarvoll K, Nido GS, Tzoulis C. Nicotinamide riboside supplementation is not associated with altered methylation homeostasis in Parkinson`s disease. iScience. 2023 Feb 27;26(3):106278.
  8. Dick F, Tysnes OB, Alves GW, Nido GS, and Tzoulis C. Altered transcriptome-proteome coupling indicates aberrant proteostasis in Parkinson’s disease. iScience. 2023 Jan 4;26(2):105925.

Read article: Isolated REM Sleep Behavior Disorder – A Unique Opportunity for Prevention in Parkinson’s Disease

Last updated 4/2/2025