Our Research Strategy

Research Goal: Fund studies exploring Alpha-1 Antitrypsin's therapeutic potential beyond traditional AATD treatment.

Focus Areas: identified in Mark Egly's 2020 patent filing

• Autoimmune Disease Management - Clinical trials for AAT in treating the 152 autoimmune diseases
• Cancer Prevention and Metastasis Inhibition - Investigating AAT's role in preventing cancer development and spread through inflammation control
• Neurological Protection - Studies on AAT's neuroprotective effects in Alzheimer's, ALS, MS, and other neurodegenerative conditions
• Acute Inflammatory Events - AAT therapy for sepsis, ARDS, cytokine storm, and other life-threatening inflammatory conditions
• Cardiovascular Disease Prevention - Vascular inflammation control and atherosclerosis prevention
• Wound Healing Enhancement - Accelerated recovery and reduced scarring through controlled inflammation

Why It Matters: These applications can help millions of people who don't have AATD but could benefit from AAT's protective properties.

Research Goal: Develop strategies to prevent disease manifestation through proactive AAT supplementation.

Key Questions We're Exploring:

• Can maintaining optimal AAT levels prevent the development of autoimmune diseases?
• What AAT threshold levels provide protection against various conditions?
• How can we identify individuals who would benefit from preventive AAT therapy?
• What environmental factors deplete AAT, and how can we mitigate them?
• Can AAT prevent disease progression in early-stage patients before irreversible damage occurs?

Target Populations:

• Individuals with genetic risk factors (carriers)
• People exposed to AAT-depleting environments (pollution, smoke, toxins)
• Patients with early signs of inflammatory conditions
• Family members of AATD patients
• High-risk populations for autoimmune diseases

Innovation: Moving from reactive treatment to proactive prevention—stopping disease before it starts.

Research Goal: Fund development of Alpha-1 Antitrypsin sources beyond human blood and plasma donation.

Critical Need: Current AAT augmentation therapy relies entirely on pooled human plasma—a limited, expensive, and potentially scarce resource. Expanding production capabilities is essential for broader therapeutic access.

Promising Approaches:

• Recombinant AAT Production - Using genetically engineered cell lines (CHO cells, transgenic animals, plants)
• Synthetic Biology - Engineering microorganisms to produce human AAT
• Plant-Based Production - Rice, tobacco, or other plant expression systems
• Gene Therapy - Enabling patients to produce their own functional AAT
• Modified AAT Variants - Engineering enhanced versions with improved stability or potency

Impact: Alternative production could dramatically reduce costs, increase availability, and enable treatment for millions currently without access.

Research Goal: Establish more precise medical definitions and diagnostic criteria for AATD as a systemic condition.

Current Problem: AATD is narrowly defined based on severe genetic deficiency and lung/liver manifestations, excluding:

• Moderate deficiency with systemic effects
• Carrier states with health implications
• Functional deficiency despite normal genetic testing
• Environmental or acquired AAT depletion
• Varying clinical presentations across different organ systems

Research Needs:

• Expanded Diagnostic Criteria - Beyond just genotype and serum levels
• Clinical Phenotyping - Understanding the full spectrum of disease manifestations
• Functional Testing - Measuring AAT activity, not just quantity
• Risk Stratification - Identifying who needs treatment based on comprehensive health assessment
• Systemic Definition - Recognizing AATD as affecting multiple organ systems simultaneously

Goal: Create diagnostic standards that capture the true scope of AAT-related disease, ensuring no patient falls through the cracks.

Research Goal: Map all tissues and systems affected by uncontrolled neutrophil elastase when AAT is deficient.

Mark's Insight: If insufficient Alpha-1 Antitrypsin fails to protect lung tissue, it logically fails to protect other tissues throughout the body.

Target Areas for Investigation:

Bone Marrow and Blood Formation

• Effect on thrombospondin-1 and hematopoiesis
• Impact on blood cell development and maturation
• Connection to anemia and blood disorders

Vascular System

• Endothelial damage and atherosclerosis
• Blood vessel integrity and aneurysm formation
• Microvascular complications

Connective Tissues

• Cartilage degradation in joints
• Skin integrity and panniculitis
• Ligament and tendon health

Neurological Tissues

• Blood-brain barrier integrity
• Neuronal protection and synaptic health
• Myelin preservation in MS and other demyelinating conditions

Reproductive Health

• Placental function and pregnancy complications
• Fertility and reproductive tissue protection

Renal System

• Kidney tissue protection
• Glomerular function preservation

Comprehensive Mapping: We seek to identify every tissue vulnerable to neutrophil elastase attack, creating a complete picture of AAT's protective role throughout the body.

Research Goal: Demonstrate how adequate AAT levels can prevent development of secondary diseases and complications.

Hypothesis: Many "comorbidities" in various diseases may actually be manifestations of inadequate AAT protection against inflammatory tissue damage.

Research Questions:

• Can AAT prevent common comorbidities in diabetes (cardiovascular disease, neuropathy, nephropathy)?
• Does AAT reduce cancer risk in patients with chronic inflammatory conditions?
• Can AAT prevent cognitive decline in patients with systemic inflammation?
• Does AAT reduce infection severity and complications?

Potential Impact: Preventing comorbidities could dramatically improve quality of life and reduce healthcare costs across numerous patient populations.

We support research that:

• Builds on Mark Egly's patent findings and discoveries
• Addresses clear hypotheses about AAT's protective mechanisms
• Proposes rigorous experimental design
• Includes measurable outcomes and endpoints
• Demonstrates clinical relevance

No idea is too novel for us to consider. We especially welcome:

• Unconventional applications of AAT therapy
• Cross-disciplinary approaches
• Studies connecting previously unrelated conditions
• Explorations of AAT in rare or understudied diseases
• Preventive strategies not yet tested

We support:

• Academic Researchers - University labs and research institutions
• Industry Scientists - Pharmaceutical and biotech companies of all sizes
• Small Biotech Firms - Innovative startups with promising approaches
• Large Pharmaceutical Companies - Established firms with development capacity
• Clinical Researchers - Physician-scientists conducting patient-centered research
• Basic Science Labs - Fundamental mechanism studies

Basic Research

• Molecular mechanisms of AAT function
• Cellular effects of AAT deficiency
• Genetic studies and variant analysis
• Animal models of disease

Translational Research

• Bridge from bench to bedside
• Biomarker development
• Drug formulation and delivery
• Proof-of-concept studies

Clinical Research

• Human trials of AAT therapies
• Observational studies and registries
• Outcome tracking and epidemiology
• Comparative effectiveness studies

• AAT in Autoimmune Diseases - Clinical trials for specific conditions (RA, lupus, MS, IBD, etc.)
• Cancer Metastasis Prevention - AAT's role in preventing cancer spread
• Alternative AAT Production - Scalable, cost-effective manufacturing methods
• Alzheimer's and Neurodegeneration - Neuroprotective mechanisms and clinical trials
• Preventive Protocols - Early intervention strategies for at-risk populations
• Parkinson's Disease - Neuroprotective effects and therapeutic potential

• Bone Marrow and Hematopoiesis - Blood cell formation and protection
• Cardiovascular Applications - Vascular protection and disease prevention
• Acute Inflammatory Conditions - Sepsis, ARDS, cytokine storm management
• Diagnostic Innovation - Better tools for identifying who needs AAT therapy
• Pediatric Applications - Early intervention for children with AATD or at-risk genotypes

• Long COVID and Post-Viral Syndromes - AAT for chronic inflammatory sequelae
• Organ Transplant - AAT for rejection prevention and graft protection
• Surgical Recovery - Enhanced healing and reduced complications
• Environmental Medicine - Protection against pollution, toxins, and occupational exposures
• Sports Medicine - Injury recovery and inflammation management

All research should consider:

• Quality of life improvements
• Functional capacity enhancement
• Symptom reduction and disease modification
• Long-term health trajectories
• Patient-reported outcomes

We expect:

• Appropriate controls and comparisons
• Adequate statistical power
• Peer review and publication
• Data transparency and sharing
• Ethical conduct and patient protection

We encourage:

• Multi-institutional studies
• International collaborations
• Cross-disciplinary teams
• Data sharing through registries
• Open-access publication when possible

The Mark Egly Foundation is particularly interested in research exploring Alpha-1 Antitrypsin in conditions never before associated with AAT deficiency.

Examples of Frontier Research:

• Psychiatric Conditions - Inflammation's role in depression, anxiety, schizophrenia
• Metabolic Disorders - AAT in diabetes, metabolic syndrome, obesity-related inflammation
• Infectious Disease Complications - AAT modulating immune response to infections
• Age-Related Conditions - Inflammaging and healthspan extension
• Dermatological Applications - Skin barrier function and wound healing
• Ophthalmologic Conditions - Eye inflammation and retinal protection
• Dental Health - Periodontal disease and oral inflammation

Our Philosophy: Any condition with an inflammatory or neutrophil elastase-mediated component is worth investigating.

If you have a research proposal aligned with our priorities:

• Review Our Priorities - Ensure alignment with our strategic focus areas
• Prepare a Concept Paper - Outline hypothesis, methods, outcomes, and budget
• Demonstrate Clinical Relevance - Show potential patient benefit
• Contact Us - Submit through our website or reach out directly

• Clear research question and hypothesis
• Connection to Mark Egly's discoveries or AATD research
• Experimental design and methodology
• Timeline and milestones
• Budget and funding needs
• Investigator qualifications and institutional support
• Potential impact on patient care

We're open to:

• Co-funding arrangements with other foundations or agencies
• Industry partnerships for drug development
• Academic collaborations with research universities
• Clinical trial networks for multi-site studies
• International research consortia

• Facilitating the "Uniting Doctors" research network
• Supporting publication of findings
• Hosting symposia and research conferences
• Creating databases and patient registries
• Educational programs based on research findings

Through strategic funding and collaboration, the Mark Egly Foundation aims to:

Transform Medical Practice

• Change standards of care for AATD and related conditions
• Enable prevention of diseases currently considered inevitable
• Provide new treatment options for millions of patients

Advance Scientific Understanding

• Map the full scope of AAT's role in human health
• Identify all tissue systems requiring AAT protection
• Elucidate mechanisms linking inflammation to multiple diseases

Improve Global Health

• Make AAT therapy accessible and affordable worldwide
• Prevent suffering through early intervention
• Extend both lifespan and healthspan for affected populations

Build a Research Community

• Unite investigators across disciplines and institutions
• Foster collaboration and knowledge exchange
• Accelerate the pace of discovery through coordination

What makes our research strategy unique:

• Prevention-Focused - Stopping disease before it starts
• Broadly Applicable - Benefits extend far beyond traditional AATD
• Patient-Driven - Based on Mark's personal discoveries and lived experience
• Collaborative - Open to diverse partnerships and unconventional ideas
• Translational - Focused on real-world clinical applications
• Comprehensive - Considering AAT's role across all organ systems

The Mark Egly Foundation invites researchers, clinicians, industry partners, and institutions to join us in expanding the horizons of Alpha-1 Antitrypsin research.

Together, we can:

• Prevent diseases that have plagued humanity for centuries
• Transform treatment paradigms across multiple conditions
• Save countless lives through early intervention
• Build a comprehensive understanding of inflammation and tissue protection

The research opportunities are limitless. The potential impact is extraordinary.

For research inquiries, grant applications, or collaborative opportunities, please contact the Mark Egly Foundation through our website.

Let's change medicine together.