Summary of the Neuro4D Conference, May 19 - 20, 2025 :

The Neuro4D Conference 2025 was attended by 56 participants from 11 countries and featured 15 Academic Presentations, 5 Corporate Presentations, 8 Panel Discussions, and 13 Posters.

Chairs Gerard Griffioen, Christiane Volbracht, Neil Cashman & Lutz Fröhlich gave comprehensive overviews to their fields during their 30 min introductory presentations. Speakers had presentation slots of 15 min incl. Q&A. This year most speakers used the entire allotted time for presentation, not allowing for questions right after their talk. The chair-led session panel discussions facilitated interaction with the audience and wider discussions. In the poster session four ad hoc posters were added to the nine posters for which abstracts had been sent for publication in the program.

The highlight of the first day were a number of novel modes of drug action for treatment of neurodegenerative diseases. Targeted Protein Degradation was attempted by PROTACs and antibodies against target protein aggregates. Antibody sequence optimization was proposed for best brain and cell penetration, and intracellular activity. Transgenic antibody production inside the disease hosts (gene therapy) was also suggested to eradicate disease-inducing protein aggregates. Strategies suppressing disease protein aggregation or monomer stabilization were shown. Furthermore, multiple attempts to stabilize calcium homeostasis in neurodegenerative diseases to prevent neuronal damage and apoptosis were presented. Novel and more comprehensive mouse models were presented to better evaluate drug effects in early mild to moderate, rather than late stage disease; and taking tau-aggregate toxicity into AD models.

Another, focus of presentations and discussions was the utility of different passive immunization therapies: Stephan Schilling compared the selectivity of different antibodies against misfolded post translationally modified natural proteins, which induce disease. Neil Cashman compared selectivity of different clinical antibodies and suggested a connection between monomer and insoluble aggregate binding and the frequency of ARIA-type side effects, observed in clinical trials. A number of attending experts felt that specific binding and eradicating of small soluble protein aggregates – often called oligomers – is key to maximal disease modifying efficacy, without causing severe side effects. It was felt that strong immune reactions to the very frequent native monomers and harmless insoluble aggregates cause treatment complications.

The first day ended with a local organic wine tasting of the Sommer vineyards of Siefersheim. Most people enjoyed the variety of Pinot Blanc, Pinot Gris, Sauvignon Blanc, Riesling and Chardonnay before the BBQ dinner started on the terrace with good weather, however a bit chilly towards the end. Many discussions of the day were intensified during the evening and new collaborations were discussed.

On the second day, the focus was on early diagnosis and treatment of neurodegenerative diseases. Oliver Peters made the case for in vitro diagnosis supporting and, in the future, possibly replacing more elaborate psychiatric evaluations and expensive MRI evaluations. He suggested that fluid-based biomarkers will enable unequivocal diagnosis of neurodegenerative diseases. Walter Schulz-Schaeffer presented his now established RT-QuIC method to detect disease inducing and templating α-synuclein aggregates in biopsies of submandibular gland to confirm diagnosis of Parkinson’s disease. One of the most appreciated presentations and the poster price went to the group of Franziska Richter, who presented the nasal therapy by small RNAs to treat Parkinson’s disease in a mouse model. Pedro Martins presented first evidence for clinical benefit of levodopa treatment for patients with neurodegenerative diseases, with suspected effects on protein aggregates and disease symptoms. Lutz Fröhlich explained current regulatory guidelines of amyloid antibody treatments of the EMA. These directions significantly reduce the number of AD patients which can currently benefit from this first disease modifying therapy. Antje Willuweit stood-in for Dieter Willbold, who unfortunately got sick, and explained the ongoing PRI-002 clinical phase II trial. Intermediate results suggest that there are no side effects and we are looking forward to see efficacy data next year. Eisai’s results in the Clarity AD and AHEAD 3-45 clinical study were discussed by Oliver Peters. These results show the clear but limited efficacy in disease modification and low rates of ARIA related side effects.

In the panel discussion, clinical panelists felt that efficacy of amyloid-related therapies might be limited to 30% reduction of symptoms and disease progression for mild AD cases. They stated that novel approaches need to address additional disease processes like neuroinflammation or tau aggregate toxicity to achieve higher clinical improvements. It was agreed that any therapy must start as early as possible for maximal patient benefit, whereas later disease stages might not even justify the unavoidable risks and burden of therapy. The panel felt that only significant improvements over currently approved therapies will justify the significant development costs in neurodegenerative diseases.

Major Sponsors:

Sponsors:

Poster Prize presented at the International Neuro4D Conference 2025:

The Poster Prize 2025 was selected by all Neuro4D participants and awarded to: Isabell Drath from the Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany: ‘Nanoparticle-based nose-to-brain delivery of small RNA to reduce alpha-synuclein pathology in a mouse model of Parkinson’s disease (Thy1-αSyn)’.

Poster Download (PDF)

Evaluation Results:

Feedback was entirely positive, on the evaluation forms, as well as in person, thank you! Many participants emphasized that we should not change conference format, nor venue! We had asked if a joint excursion would be welcome to further intensify delegate interactions, which was welcome by a number of delegates, but not seen as beneficial by others. Again, it was emphasized that the interactivity and togetherness of an expert group is a major benefit of Neuro4D and fosters successful collaborations, especially in comparison to big, multi-stream and impersonal meetings.

Feedback Neuro4D Conference 2025:

Question*:	Average Score # (max 5, min1)
Did you enjoy the venue and atmosphere?	4,9
Was the venue easy to reach for you?	4,6
How did you like your hotel room and service?	4,9
Did you enjoy the meals?	4,6
Did you enjoy the local wine tasting?	4,5
Was the conference overall scientific content fulfilling your expectations?	4,6
How do you rate the quality of presentations, posters and speakers?	4,6
Does Neuro4D cover important aspects outside of existing conferences like ADPD, AAIC, SfN?	4,4
Quality of the organization, printed program and team?	4,9
Did you enjoy the breaks & poster sessions?	4,6
Did you get to know interesting new contacts?	4,7

* Open questions and their answers are not shown.
# Absence of vote was counted as lowest score ‘1’

Advisory Committee:

Rakez Kayed, UTMB, Galveston, USA
Neil Cashman, ProMIS, Vancouver, Canada
Oliver Peters, Charité, Berlin, Germany
Roger Sher, Stony Brook University, USA

Organizer:

Dr. Andreas Köpke (bioExpert)
Tel: +49 6136 957 3000
info@bioexpert.biz