Summary
BDNF has been remarkably effective in proof-of-concept studies but there has been no viable approach for delivery. This project, led by Dr. Simona Capsoni, will attempt to both develop and validate a novel, non-invasive, intranasal delivery strategy for BDNF in PWS.
Lay Abstract
1. Project Summary. The central issue this research addresses is the low level of Brain-Derived Neurotrophic Factor (BDNF) in people with PWS. BDNF is essential for growth, memory, and regulating appetite. Previous attempts to deliver BDNF required highly restrictive, invasive brain surgery. This project proposes an entirely new, non-surgical way to deliver this brain fertilizer: a nasal spray. The core of the project involves 3 steps: (a) Delivery Method: Testing if delivering BDNF through the nose (intranasally) is effective in PWS mouse models, which is a much simpler, non-invasive process. (b) Enhanced Packaging: Comparing BDNF alone with BDNF packaged within tiny, natural protective carriers called Extracellular Vesicles (EVs). These EVs are intended to act as a protective envelope, helping the BDNF stay stable, reach specific brain areas, and be more potent at a lower dose. (c) Formulation: Developing the final, optimized nasal spray formula that is safe and ready to be tested in humans.
2. Why This Research is Important? This research targets the underlying cause of multiple PWS symptoms simultaneously, in a way that is practical for patients. (a) Addressing Multiple Symptoms: BDNF affects the parts of the brain that control both the uncontrolled hunger and behavioral/psychiatric issues like anxiety and psychosis. Successful BDNF delivery aims to be a single treatment for both physical and mental health challenges. (b) Speed and Safety: Using a non-invasive nasal spray is inherently safer and much faster to translate to the clinic than complex, long-term treatments like gene therapy or surgery. It offers a more immediate potential therapeutic solution for families. (c) Precision Science: Understanding if the EV carriers truly boost BDNF's effect will not only improve PWS treatment but also advance the broader field of how to get large, complex protein drugs across the blood-brain barrier for treating any neurological disorder.
3. Next Steps Depending on the Outcomes. The path forward depends on which delivery system proves most effective in the mouse models: Option A (BDNF in EVs is highly effective): Prioritize the EV-enhanced nasal spray, finalize the human-ready formulation, and proceed to safety/toxicology studies and clinical trials for PWS. Option B (BDNF protein alone works well): Optimize the simpler BDNF protein nasal spray and follow a similar, but less complex, path to the clinic. Option C (Delivery or effect is limited): Re-evaluate the formulation components or explore alternative EV carriers to boost BDNF absorption to the brain.
4. Therapeutic Progress and Clinical Foundation. This project sets a critical foundation for therapeutic development: (a) Ready-to-Translate Drug Product: The successful BDNF/EV nasal spray creates a non-invasive, easily administered drug product closer to clinical reality. (b) New Delivery Paradigm: By validating nose-to-brain delivery using sophisticated EV carriers, the project solves the major challenge of getting complex proteins pass the brain's protective barriers. This breakthrough opens the door for similar non-invasive protein therapies for other brain disorders.
Funded Year:
2026
Awarded to:
Simona Capsoni, PhD, DVM
Amount:
$161,984
Institution:
University of Ferrara
Researcher:
Simona Capsoni, PhD, DVM
