Mark Egly Foundation

State of the Field

Current Alpha-1 Antitrypsin Research Landscape and the Path Forward

The Current Research Paradigm

The mainstream research community is currently focused on developing a cure for Alpha-1 Antitrypsin Deficiency (AATD), with particular emphasis on genetic therapies and protein folding correction. This work is both phenomenal and essential—significant strides are being made to address protein misfolding issues that originate in the liver.

Gene Therapy and Protein Folding Research

Current research priorities include:

  • Gene therapy approaches to correct the SERPINA1 gene mutations
  • Protein folding correction to address Z-variant AAT that misfolds in liver cells
  • Liver transplantation as a curative option for severe hepatic disease
  • Novel augmentation therapy formulations for improved delivery and efficacy

These advances are particularly helpful for the approximately 25% of individuals with AATD who suffer from Z-protein accumulation in the liver, putting them at significant risk for cirrhosis and liver cancer.

This research is vital and must continue.

The Mark Egly Foundation's Complementary Approach

While we fully support the pursuit of genetic cures, the Mark Egly Foundation is pioneering a parallel and equally critical path: prevention and expanded therapeutic applications.

Our Research Focus: Prevention Over Remediation

Our groundbreaking work centers on a fundamental question:

What if we could prevent AATD-related conditions from ever manifesting by maintaining proper levels of Alpha-1 Antitrypsin in everyone's body?

This preventive approach offers several advantages:

  1. Immediate Impact - Available treatments can be applied now, not decades from now
  2. Broader Application - Benefits extend beyond those with severe genetic deficiency
  3. Systemic Protection - Addresses the full range of AAT-related conditions
  4. Quality of Life - Prevents irreversible damage rather than attempting to reverse it

Beyond Traditional AATD: Expanding the Field

Therapeutic Applications in Non-Deficient Populations

Our research has uncovered that Alpha-1 Antitrypsin has significant therapeutic value even for individuals without AATD

. This represents a paradigm shift in how we understand this protein's role in human health.

Emerging Applications Include:

Autoimmune Diseases

  • Treatment potential for 152+ identified autoimmune conditions
  • Controlling neutrophil elastase-driven tissue destruction
  • Modulating inflammatory response in conditions like rheumatoid arthritis, lupus, and MS

Cancer Prevention and Treatment

  • Preventing metastasis through inflammation control
  • Protecting healthy tissue during cancer treatment
  • Reducing cancer risk in high-inflammation environments
  • Addressing the mechanisms behind secondhand smoke-related cancers

Neurological Conditions

  • Alzheimer's disease (now understood as autoimmune-related)
  • ALS (Lou Gehrig's Disease)
  • Multiple Sclerosis
  • Other neurodegenerative conditions with inflammatory components

Acute Medical Events

  • Severe COVID-19 and cytokine storm management
  • Sepsis and systemic inflammatory response syndrome (SIRS)
  • Acute respiratory distress syndrome (ARDS)
  • Post-surgical inflammation control

Chronic Inflammatory Conditions

  • Cardiovascular disease prevention
  • Chronic pain management
  • Wound healing enhancement
  • Environmental exposure protection (pollution, smoke, toxins)

Current Gaps in the Field

What Traditional Research Overlooks

While gene therapy research is promising, several critical gaps remain:

1. The Diagnostic Gap

  • Only ~10,000-15,000 identified cases in the US (estimated 100,000+ actually affected)
  • Average 8 years and 4 healthcare providers before diagnosis
  • Many patients die without ever being diagnosed
  • No routine screening protocols in place

2. The Treatment Gap

  • Strict augmentation therapy criteria exclude many who could benefit
  • Focus on severe deficiency overlooks moderate cases
  • Limited understanding of optimal treatment timing
  • Insufficient data on long-term outcomes of early intervention

3. The Knowledge Gap

  • Systemic effects of AAT deficiency remain poorly understood by most physicians
  • Connection to autoimmune diseases not widely recognized
  • Therapeutic applications beyond AATD largely unexplored
  • Limited education in medical schools and residency programs

4. The Prevention Gap

  • No strategies for preventing disease progression in early-stage patients
  • Lack of protocols for at-risk family member screening
  • Insufficient focus on environmental factor mitigation
  • Missed opportunities for proactive health management

The Mark Egly Foundation's Research Agenda

Our Multi-Pronged Approach

1. Preventive Medicine Research

  • Establishing optimal AAT levels for health maintenance
  • Identifying early biomarkers for intervention
  • Developing prevention protocols for at-risk populations
  • Studying environmental factors that deplete AAT

2. Expanded Therapeutic Applications

  • Clinical evidence for AAT in autoimmune disease treatment
  • Cancer prevention and metastasis inhibition studies
  • Neurological condition interventions
  • Acute inflammatory event management

3. Mechanistic Understanding

  • Neutrophil elastase's role in tissue destruction across multiple diseases
  • AAT's protective mechanisms beyond protease inhibition
  • Inflammatory cascade interruption points
  • Systemic effects of chronic AAT insufficiency

4. Clinical Translation

  • Bridging the gap between research discoveries and clinical practice
  • Developing practical screening and treatment protocols
  • Creating educational resources for healthcare providers
  • Documenting patient outcomes and case studies

5. Collaborative Research Initiatives

  • Partnering with leading medical institutions
  • Supporting independent research aligned with our mission
  • Facilitating the "Uniting Doctors" knowledge-sharing network
  • Contributing to scientific literature and medical education

Where the Field Needs to Go

A Vision for Comprehensive AATD Care

The future of Alpha-1 Antitrypsin research and treatment should include:

Integrated Approach:

  • Genetic cures for those with severe deficiency (current focus)
  • Augmentation therapy with expanded access (bridging solution)
  • Preventive strategies for all at-risk individuals (our focus)
  • Therapeutic applications for broader populations (emerging field)

Universal Screening:

  • Routine testing as part of standard health screening
  • Targeted testing for symptomatic individuals
  • Family cascade testing protocols
  • Newborn screening consideration

Early Intervention:

  • Treatment before irreversible damage occurs
  • Proactive monitoring and management
  • Lifestyle and environmental modifications
  • Regular assessment and optimization

Holistic Understanding:

  • Recognition of systemic impacts
  • Integration across medical specialties
  • Comprehensive patient care models
  • Long-term outcome tracking

Current Research Partnerships and Initiatives

The Mark Egly Foundation is actively engaged in:

  • Academic Collaborations - Working with research institutions on AAT studies
  • Clinical Networks - Building physician networks for knowledge exchange
  • Patient Registries - Documenting outcomes and treatment responses
  • Publication Support - Contributing to peer-reviewed medical literature
  • Educational Programs - Training healthcare providers on latest findings
  • Advocacy Efforts - Promoting policy changes for expanded access

The Complementary Nature of Research Paths

Gene Therapy Research (Current Mainstream Focus):

  • Long-term solution for genetic deficiency
  • Potentially curative but years or decades away
  • Benefits those with severe deficiency
  • High complexity and cost

Prevention and Augmentation (Mark Egly Foundation Focus):

  • Immediate application with existing therapies
  • Benefits current patients and broader populations
  • Prevents damage rather than attempting reversal
  • Accessible and implementable now

Both approaches are essential. Gene therapy may one day cure AATD at its genetic root, but in the meantime, millions of people need help today. Our preventive and therapeutic approach saves lives now while we wait for ultimate genetic solutions.

Moving Forward: A Call for Balanced Research Investment

The field needs:

  1. Continued gene therapy research - Don't abandon the pursuit of a cure
  2. Expanded prevention research - Invest in strategies that help patients now
  3. Broader therapeutic exploration - Investigate AAT applications beyond AATD
  4. Clinical translation - Bridge the gap between discovery and practice
  5. Patient education - Empower individuals with knowledge and resources
  6. Provider training - Ensure physicians can identify and treat AATD effectively

Our Commitment to Advancing the Field

The Mark Egly Foundation will continue to:

  • Pursue cures alongside the broader research community
  • Advance treatment options through clinical research and advocacy
  • Prevent disease manifestation through early identification and intervention
  • Explore novel applications including cancer metastasis prevention
  • Share knowledge openly with medical professionals and the public
  • Support patients through education, resources, and community building

The state of the field is evolving rapidly. While traditional research pursues genetic cures, the Mark Egly Foundation is ensuring that today's patients don't have to wait decades for tomorrow's solutions. Through prevention, early intervention, and expanded therapeutic applications, we're changing lives now—while supporting the long-term pursuit of a permanent cure.