Revolutionizing neurodegenerative disease treatment through CDNF and HER-096 therapies
For the millions of people living with Parkinson's disease worldwide, available treatments have offered symptomatic relief but nothing that stops the relentless progression of the condition. This gap between managing symptoms and truly modifying the disease has represented one of the most significant challenges in modern neurology.
Enter Herantis Pharma, a clinical-stage biotechnology company daring to approach neurodegenerative diseases differently. Their pioneering work on CDNF and HER-096 represents a potentially revolutionary class of therapies that could protect and even restore damaged neurons in the brain. This isn't just another dopamine regulator—it's science that aims to alter the very course of Parkinson's disease 5 .
Herantis's research focuses on what scientists call "disease-modifying therapies"—treatments designed to address the underlying biological processes of a disease rather than just its symptoms. In Parkinson's, this means finding ways to protect the dopamine-producing neurons whose degeneration causes the disease's characteristic movement symptoms 1 3 .
A naturally occurring protein in the human body that has shown remarkable neuroprotective and neurorestorative properties in preclinical models. CDNF is considered an "unconventional neurotrophic factor" because its mechanism of action differs significantly from traditional neurotrophins 5 .
Recent groundbreaking research has shed light on how CDNF actually works in the brain. A 2024 study published in Nature Communications revealed that CDNF interacts with GRP78, a critical protein regulator of the unfolded protein response (UPR) pathway .
The UPR is essentially the cell's quality control system for protein production. When this system detects misfolded proteins—a common problem in neurodegenerative diseases including Parkinson's—it can trigger cellular stress responses that ultimately lead to neuron death. The research demonstrated that CDNF binds directly to GRP78's nucleotide-binding domain, and this interaction appears essential for CDNF's neuroprotective effects .
This discovery is particularly significant because it provides a structural basis for understanding how CDNF protects neurons from the cellular stress that would normally kill them.
To unravel how CDNF interacts with GRP78, researchers employed advanced structural techniques that allowed them to visualize these molecular interactions at an unprecedented level of detail :
Size Exclusion Chromatography-Small Angle X-ray Scattering for analyzing protein complex shapes
Nuclear Magnetic Resonance for determining molecular structure and dynamics
Generating and evaluating structural models of protein complexes
Modifying specific amino acids to determine essential binding sites
The experimental results provided compelling evidence of a direct molecular interaction between CDNF and GRP78.
Perhaps most significantly, when researchers mutated the specific CDNF residues involved in GRP78 binding, the resulting protein not only showed impaired binding capability but, crucially, lost its neuroprotective activity in mesencephalic neuron cultures. This strongly suggests that the interaction with GRP78 isn't incidental but fundamental to CDNF's ability to protect neurons .
One of the most significant hurdles in treating brain disorders is the blood-brain barrier—a protective cellular layer that prevents most drugs from entering the brain from the bloodstream. Early approaches with CDNF required direct administration into the brain, a complex medical procedure 5 .
HER-096 represents a strategic solution to this challenge. As a smaller peptidomimetic molecule, it's designed to be administered subcutaneously (under the skin) yet still reach its target in the central nervous system. Recent Phase 1b clinical trials confirmed that HER-096 successfully crosses the blood-brain barrier and remains in the central nervous system long enough to potentially exert therapeutic effects 1 .
The Phase 1b trial of HER-096, reported in September 2025, achieved all its primary objectives, demonstrating good tolerability and safety in both healthy volunteers and patients with Parkinson's disease.
Status: Completed
Key Findings: Good safety and tolerability; blood-brain barrier penetration
Next Steps: Progress to Phase 1b
Status: Completed (2025)
Key Findings: Good tolerability and safety; determined optimal dosing
Next Steps: Advance to Phase II
Status: Planned (2026)
Key Findings: To investigate long-term safety and preliminary efficacy
Next Steps: Potential partnership agreement
While the scientific foundation of Herantis's approach is compelling, the path from promising mechanism to approved medicine remains challenging.
Current funding is sufficient only until Q2 2026, making the securing of additional resources a priority.
The true test will come when HER-096 is evaluated for its ability to actually slow Parkinson's progression.
Potential for extending their approach to other neurodegenerative diseases, including Alzheimer's disease.
Herantis Pharma represents a fascinating convergence of structural biology insight and therapeutic innovation. Their work on the CDNF-GRP78 interaction mechanism provides a robust scientific foundation for what could become the first truly disease-modifying treatment for Parkinson's disease.
The journey of HER-096 from a structural insight about protein interactions to a potential life-changing medicine exemplifies how deepening our understanding of fundamental biological processes can open new avenues for treating some of medicine's most challenging conditions.