Lysosomal dysfunction biomarkers for PD
How would you propose to identify a CSF-, blood-, or urine-based biomarker to stratify early Parkinson’s disease patients according to the degree of lysosomal dysfunction?
Thomas Ciossek
Project Leader RBB
Discovery Research Boehringer Ingelheim
Call for proposals: All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants based on mutually agreed funding terms.
More information
Parkinson’s disease (PD) is a chronic, progressive neurological disorder that primarily affects motor function. It is caused by the gradual loss of dopamine producing neurons in the substantia nigra, a brain region critical for movement control. This neurodegeneration leads to characteristic motor symptoms, such as tremors, muscle rigidity, bradykinesia (slowed movement), and impaired balance.
Approximately 10–15% of PD patients carry a known genetic risk factor, such as mutations in LRRK2, PINK1 or GBA. However, for most patients, no clear genetic association has been identified to date. PD is therefore considered a multifactorial disease, arising from a complex interplay of genetic susceptibility, environmental influences, and biological processes. Multiple pathomechanisms — including lysosomal and mitochondrial dysfunction, inflammatory processes, and impaired protein homeostasis — are hypothesized to contribute to disease onset and progression. These distinct mechanisms can ultimately converge into a clinically similar disease phenotype despite differing underlying causes.
To enable the development and effective evaluation of mechanism targeted therapies, it is highly desirable to stratify prodromal / early PD patients into biologically defined subgroups. Such stratification would allow novel therapies to be tested in patient populations where their specific mode of action has the highest likelihood of producing meaningful clinical benefit.
Notably, a significant portion of risk genes identified in PD patients have been associated with lysosomal functions, pointing to a critical role of lysosomes in PD. Despite this, no readily accessible biomarker (e.g., blood‑ or cerebrospinal fluid (CSF) -based) has yet been identified that reliably reflects lysosomal dysfunction at an early stage of PD. An exception is the reported increase in urinary BMP levels in patients carrying pathogenic LRRK2 mutations, highlighting both the potential and the current limitations of biomarker development in this area.
We invite innovative proposals for non-invasive biomarker approaches aimed at identifying lysosomal markers in CSF, blood, urine, tears, saliva, or other biofluids or tissues of Parkinson’s disease patients, using analytes such as proteins, lipids, metabolites, or related measures (excluding sequencing of genetic variants), in comparison with age-matched individuals without evidence of neurodegenerative disease. While the primary focus is on fluid-based approaches, imaging-based methodologies are also within scope but are considered of secondary priority.
Submissions should focus on approaches that enable stratification of patients in whom lysosomal dysfunction is a key driver of disease onset.
Proposals are expected to outline innovative concepts, technologies, or strategies with evidence of biological relevance, analytical robustness, and potential for clinical translation.
Innovative solutions and approaches must meet all of the following criteria:
- The biomarker needs to be relevant for patients in the prodromal and/or early PD stage
- Should make use of easily accessible human patient material
- The approach needs to be tailored to detect changes associated with lysosomal dysregulation and/or function
- Targeted biomarkers need to allow for quantitative assessment
- Outcome should be translatable, i.e., measurable in preclinical animal models (e.g., rodents) and/or relevant in vitro disease models (iPSC-derived cell/organoid systems) as well
While the primary focus is on fluid-based approaches, imaging-based methodologies are also within scope but are considered of secondary priority.
- Biomarkers that only qualify for mid- to severe/end-stage PD patients
- Sequencing/genotyping for known PD risk factors / genetic variants
- GWAS or related screens
- Brain biopsy-related or postmortem assessments
- No invasive procedures will be considered, except for CSF or skin sampling.
- in silico biomarkers inferred from computational models or simulations of behavioral observations and systems biology data (e.g., lung or cardiac function)
- in silico biomarkers derived from imaging modalities (MRI, PET, CT, ultrasound) and digital data sources (e.g., wearables, sensors, smartphones)
If your project is selected, you will have the opportunity to directly collaborate with Boehringer's Neuroscience Research experts.
You can also expect appropriate funding for the prospective collaboration period. Your exact funding request should be outlined in your proposal. As a framework, we suggest that your initial funding request is structured in milestones and does not exceed 300,000 euros per submitted project in total (150,000 euros per year for a maximum period of 2 years, including direct, indirect, and overhead costs). Please note that depending on the complexity and maturity of a proposed model and the degree of validation, different budget terms could be negotiated with you.
Our collaboration agreement will provide full transparency about each partner’s rights & obligations (including intellectual property rights). As part of the agreement, you will be encouraged to publish following the collaboration agreement (to be negotiated in good faith).
The proposal needs to be highly feasible, should be based on established and existing methods, essays, and involve tools / reagents that are either available or which can be easily produced. We expect that the project will be executed in your laboratory and take advantage of existing technologies and methods.
In addition, we are seeking research collaboration proposals that contain:
- A well-structured proposal outlining a new and compelling scientific approach.
- Outlining of the technical feasibility, and potentially existing data or previous publications that support feasibility / experience with outlined technology, based on existing and established assays.
- Your exact funding request should be outlined in your proposal based on a well-thought-through project. The project should be structured in milestones and planned with key decision points (clear Go/No-Go criteria). The funding request for the initial milestones resulting in a Go/No-Go decision should not exceed 300,000 euros per submitted project in total (150,000 euros per year for a maximum period of 2 years, including direct, indirect, and overhead costs). Please note that depending on the complexity and maturity of a proposed model and the degree of validation, different budget terms could be negotiated with you.
- Proven track record in the required field of expertise.
- Ability to implement the outlined solution as part of a scientific collaboration project with Boehringer Ingelheim including access to a wet laboratory.
- Proposals with an anticipated execution time of two years will be prioritized.
Please use our answer submission template to provide a 2–3 page non-confidential proposal (available for download here).
If confidential data exists that would strengthen the proposal, please indicate that information is available to share under a Confidential Disclosure Agreement (CDA). If we find the non-confidential concept proposal sufficiently interesting, we will execute a CDA for confidential discussions.
We are currently seeking answers for the following scientific question: How would you propose to identify a CSF-, blood-, or urine-based biomarker to stratify early Parkinson’s disease patients according to the degree of lysosomal dysfunction?
All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants based on mutually agreed funding terms.
We can only accept research proposals if they arrive no later than September 1, 2026, 11:59 pm PST.
