Understanding Natural History: How RHI Tracks Hearing Loss Progression to Revolutionize Gene Therapy
In this groundbreaking presentation, RHI CEO Jim Ayala reveals how understanding the natural progression of genetic hearing loss—from initial symptoms to complete deafness—is enabling the development of targeted gene therapies that could save patients’ hearing before it’s too late.
What is Natural History in Gene Therapy Development?
Jim Ayala explains:
“We’re trying to understand more about what’s called the natural history of the disease—in other words, how does the disease progress from the time a patient realizes that their hearing is going bad or they’re not hearing as well to the time that they actually would go deaf.”
💡 Key Insight
Natural history studies create a comprehensive timeline of disease progression, providing the critical baseline data needed to measure gene therapy effectiveness and determine optimal intervention timing.
The Patient Journey: Understanding Disease Progression
Disease Timeline:
“What we know about the disease right now is that typically patients are born with normal hearing and then usually in their late teens and early 20s they start to lose their hearing.”
Typical Disease Progression Timeline
Current Treatment Options and Their Limitations
Available Interventions:
“They will be given typically two options: you have the options of hearing aids and if your hearing is really bad you potentially could qualify for a cochlear implant.”
Treatment Progression Path
- Hearing Aids
- First-line intervention
- Effectiveness diminishes as disease progresses
- Cannot prevent continued deterioration
- Cochlear Implants
- Surgical intervention for severe cases
- Electronic device with external receiver
- Direct stimulation of inner ear
The Critical Challenge:
“Because this disease affects multiple parts of the inner ear physiology—hair cells as well as nerve cells—their hearing continues to get worse even with a cochlear implant.”
🔬 Scientific Breakthrough
This multi-cellular pathology explains why current interventions fail and highlights the need for gene therapy approaches that can address the root genetic cause.
RHI’s Revolutionary Natural History Approach
Data Collection Strategy:
“What we’re doing at Rescue Hearing is we are taking data from patient records that have tested positive for this specific genetic mutation.”
RHI’s Comprehensive Research Framework
Multi-Modal Approach:
“In addition to our mouse data, in addition to our in vivo data, our cell data, we’re also doing natural history studies on individual patients, documenting their journey from the beginning when they began to lose their hearing to the point where they go deaf.”
🎯 Strategic Objective
RHI-001 aims to intervene before patients reach the point of deafness, potentially preserving hearing function through targeted gene therapy.
Regulatory Significance: Why FDA and EMA Need Natural History Data
Regulatory Requirements:
“We will present to the regulatory authorities of the FDA and the EMA because the regulatory authorities also want to know how does this disease progress.”
Critical Regulatory Applications:
- Endpoint Selection: Natural history data helps define clinically meaningful outcomes
- Trial Design: Informs patient selection criteria and treatment timing
- Efficacy Demonstration: Provides baseline for comparison without placebo groups
- Safety Monitoring: Distinguishes drug effects from natural disease progression
Building the Evidence Base:
“RHI is in the process of amassing a database of patients who have this mutation and tracking the natural history of this disease as it progresses.”
The Impact: Why This Matters for Patients
🌟 Patient Hope
By understanding exactly how and when hearing loss progresses in patients with specific genetic mutations, RHI can:
- Identify the optimal treatment window
- Develop targeted interventions before irreversible damage
- Provide hope for preserving natural hearing function
- Create evidence-based treatment protocols
Looking Forward: The Future of Gene Therapy for Hearing Loss
Natural history studies represent the foundation upon which successful gene therapies are built. RHI’s comprehensive approach—combining patient data, preclinical research, and regulatory strategy—exemplifies how understanding disease progression enables the development of transformative treatments.
For patients facing genetic hearing loss, this research offers something that current treatments cannot: the possibility of addressing the root cause of their condition before it’s too late.