Description of the platform

In the last decade it has become clear that the underlying disease pathologies of Alzheimer's disease (AD) and Parkinson's disease (PD) start to accumulate several decades before onset of overt symptoms. We can now use biomarkers to reliably detect these disease pathologies (e.g., amyloid-beta, tau and alpha-synuclein) even during pre-symptomatic and prodromal phases of the disease (Hansson. Nature Medicine, 2021). In the last years it has become evident from both basic and clinical research that disease-modifying therapies are likely to be much more efficient when initiated during these early pre-symptomatic or prodromal phases of AD and PD, i.e., before widespread and irreversible neurodegeneration has already occurred. A couple of such randomized controlled trials are already ongoing in the USA for pre-symptomatic AD (e.g., the NIH-funded A4 and AHEAD 3-45 studies), and similar studies are planned for prodromal PD. However, Europe should be part of this development, and in order to be competitive we need to establish Trial Ready Cohorts, consisting of individuals with either pre-symptomatic or prodromal disease that subsequently can quickly enter randomized controlled trials evaluating novel pharmacological treatments. So far, no such cohorts exist in Scandinavia.

Consequently, we have set up a clinical platform composed of 3.5 research nurses, 1 medical doctor, and 1 research coordinator that will establish 2 new trial-ready cohorts:
a) Individuals with pre-symptomatic AD. About 2,000-3,000 cognitively normal individuals in Skåne (aged 50-80 years) are screened with blood-based P-tau217 and APOE genotyping (Palmqvist et al, Nature Medicine, 2021; Palmqvist et al, JAMA, 2020) to detect appr. 600 cases with elevated risk of having pre-symptomatic AD. The latter undergo CSF and PET investigations for amyloid-beta pathology to determine which of these persons who indeed has pre-symptomatic AD. The aim is to recruit 400 individuals for this pre-symptomatic AD trial-ready cohort.

b) Individuals with prodromal PD. We aim to include 100 individuals with idiopathic REM-sleep Behavioral Disorder (iRBD) who have Lewy Body disease pathology in the brain. It has recently been shown that the majority of individuals with iRBD are positive when CSF is analyzed for alpha-synuclein seeding aggregation assays (RT-QuIC; Iranzo et al, Lancet Neurology, 2021), and this accurately predicts future development of clinical Lewy Body disease (i.e., PD or DLB). We advertise for individuals with iRBD symptoms, which is confirmed with polysomnography, and Lewy Body pathology is confirmed with a CSF-based alpha-synuclein RT-QuIC assay. Those with confirmed Lewy Body pathology and iRBD are included in this prodromal PD trial-ready cohort. We also include 100 patients with newly diagnosed PD in this trial ready cohort.

This platform will establish two trial ready cohorts that can help MultiPark to achieve its strategic goals in several ways:

1) To understand the origins and progression of neurodegenerative disease
Skin-biopsies, plasma samples and CSF samples can all be used to perform omics analyses or targeted analyses, and skin-biopsies can also be used for reprogramming (e.g., into iN cells). Because the samples are from individuals with very early disease, it will help MultiPark researchers to better understand the earliest disease stages of PD and AD.

2) To develop early and differential diagnostics and prognostics
This platform will be useful for all aims under this heading. Samples and images collected can be used to develop: a) effective accurate and cost-effective diagnostics, and b) novel methods for detecting therapeutic effects of novel interventions on neurodegeneration and plasticity. Further, novel digital tools will be used to improve c) methodologies for quantitative monitoring of neurological, cognitive and psychiatric deficits and symptoms.

3) To create new therapeutic approaches for prevention, disease modification and management of unmet medical needs
This is the most important aim of this novel platform. By establishing Trial-Ready cohorts, we will substantially improve "our ability to conduct clinical trials by supporting important infrastructure and develop more refined methods to evaluate relevant target engagement of novel disease-modifying drugs in the human brain." We further think that this platform would greatly increase MultiPark's interactions with the international pharmaceutical companies.

The platform will make Lund one of the most competitive sites in the world for clinical trials in pre-symptomatic and prodromal AD/PD. Such Trial-Ready cohorts do not exist in Scandinavia and are extremely rare even from a global perspective. As stated above, we think this would greatly increase MultiPark's interactions with the international pharmaceutical companies. It would make Multipark a highly attractive collaboration partner in research initiatives concerning projects aiming for disease modification of neurodegenerative disease worldwide. 

How can I use the platform?
Researchers employed by Skåne University Hospital or Lund University will be able to apply to get access individuals (i.e., with either preclinical/prodromal Alzheimer’s disease or prodromal/mild Parkinson’s disease) who can be asked to participate in therapeutic trials headed by the researchers and sponsored by either Skåne University Hospital or Lund University.

The cohorts are still under development, and more details will be provided once they are ready for use.  

Prerequisites for future applications from applicants
Approvals from both the Swedish Ethical Review Authority and the Medical Products Agency for the therapeutic trial should be in place with Region Skåne or Lund University as the sponsor.

• There is no need for co-funding, if the researchers themselves take responsibility for contacting the SweTRAP study participants with information regarding their new therapeutic trial.

Detailed instructions for applications will be published when the cohorts are ready for use.