Our Research Strategy

Funding Focus: Research demonstrating how Alpha-1 Antitrypsin can prevent and treat comorbidities across multiple disease states.

Key Research Questions:

• Can AAT supplementation prevent common comorbidities before they develop?
• Which comorbidities respond best to AAT therapy?
• What are the optimal dosing and timing strategies for prevention?
• How does AAT affect disease progression in patients with multiple conditions?

Target Conditions:

• Cardiovascular Comorbidities - Prevention of heart disease in inflammatory conditions
• Metabolic Complications - Diabetes-related tissue damage and complications
• Renal Dysfunction - Kidney protection in systemic diseases
• Cognitive Decline - Preventing neurological complications of chronic inflammation
• Cancer Development - Reducing cancer risk in chronic inflammatory states

Why This Matters: Preventing comorbidities is more effective and less costly than treating advanced disease. AAT's anti-inflammatory properties may prevent the cascade of complications that burden patients with chronic conditions.

Funding Focus: Clinical trials and mechanistic studies exploring AAT therapy for the 152 autoimmune diseases identified in Mark Egly's 2020 patent filing.

Priority Autoimmune Conditions for Study:

• Rheumatoid arthritis
• Systemic lupus erythematosus (SLE)
• Multiple sclerosis
• Inflammatory bowel disease (Crohn's, ulcerative colitis)
• Type 1 diabetes
• Psoriasis and psoriatic arthritis
• Sjögren's syndrome
• Scleroderma
• Myasthenia gravis
• Guillain-Barré syndrome
• And 142 additional autoimmune conditions

Research Approaches We will Fund:

• Small pilot studies establishing proof-of-concept
• Multi-center clinical trials for promising applications
• Biomarker studies identifying who will respond to AAT
• Mechanistic research explaining AAT's effects in specific conditions
• Combination therapy studies (AAT with standard treatments)

Funding Focus: Understanding and preventing cancer development and spread through AAT's anti-inflammatory mechanisms.

Critical Research Areas:

• Primary Prevention - Can AAT reduce cancer incidence in high-risk populations?
• Metastasis Inhibition - Does AAT prevent cancer spread by controlling inflammation?
• Treatment Support - Can AAT protect healthy tissue during chemotherapy/radiation?
• Inflammation-Driven Cancers - Targeting cancers linked to chronic inflammation

Example Research Projects:

• AAT in preventing colon cancer in inflammatory bowel disease patients
• AAT reducing lung cancer risk in COPD patients
• AAT preventing breast cancer metastasis
• AAT protecting against pancreatic cancer in chronic pancreatitis

Critical Need: Current AAT augmentation therapy relies exclusively on pooled human plasma—a limited, expensive, and potentially insufficient resource. Alternative production methods are essential for:

• Global accessibility
• Cost reduction
• Scalability to treat millions
• Elimination of infectious disease transmission risk
• Consistent product quality

Funding Priorities:

We will fund research in:

Cell-Based Production

• CHO (Chinese Hamster Ovary) cell expression systems
• HEK293 (human embryonic kidney) cell lines
• Yeast expression systems (Pichia pastoris)
• Bacterial expression platforms
• Insect cell culture systems

Transgenic Organism Production

• Transgenic animals (goats, sheep, cattle) producing AAT in milk
• Transgenic chickens producing AAT in eggs
• Safety and efficacy studies for animal-derived AAT

Plant-Based Bioreactors

• Rice grain expression systems
• Tobacco plant production
• Moss bioreactors (Physcomitrella patens)
• Algae-based production
• Scale-up and purification methods

In Vivo AAT Production:

• AAV (adeno-associated virus) gene therapy delivering functional SERPINA1 gene
• CRISPR-based correction of Z-allele mutations
• Liver-directed gene therapy enabling natural AAT production
• Long-term safety and durability studies

We will fund development of:

• Enhanced AAT variants with improved stability
• Modified AAT with extended half-life
• AAT fusion proteins with enhanced delivery
• Oral formulations and alternative delivery routes
• Inhaled AAT for direct lung delivery

Expected Impact: Successful development of alternative production methods could reduce costs by 90% and make therapy accessible to millions currently unable to afford treatment.

Current Problem: AATD is too narrowly defined, focusing only on:

• Severe genetic deficiency (ZZ genotype)
• Low serum AAT levels (typically

Research We'll Fund:

Genetic and Molecular Characterization

• Rare allele variants and their clinical significance
• Carrier states (MZ, SZ) and associated health risks
• Genetic modifiers affecting disease expression
• Epigenetic factors influencing AAT production
• Gene-environment interactions

Functional Assessment

• AAT activity testing (not just quantity)
• Neutrophil elastase levels and activity
• Oxidative modification of AAT (making it dysfunctional)
• Tissue-specific AAT levels vs. serum levels
• AAT consumption rates in inflammatory states

Clinical Phenotyping

• Systemic manifestations beyond liver and lungs
• Mild to moderate deficiency health impacts
• Late-onset vs. early-onset disease patterns
• Gender differences in disease expression
• Ethnic and population-specific variations

We seek research defining:

• Severe Deficiency (ZZ, null) - Traditional definition
• Moderate Deficiency (SZ, MZ with symptoms) - Requires new criteria
• Functional Deficiency - Normal genetics but inadequate AAT activity
• Acquired Deficiency - Environmental depletion of AAT
• Relative Deficiency - Insufficient AAT for individual's inflammatory burden

Goal: Create diagnostic standards that identify ALL individuals who could benefit from AAT therapy, not just those with the most severe genetic deficiency.

Research Philosophy: If insufficient AAT fails to protect lungs, it logically fails to protect ALL tissues throughout the body.

Funding Focus: Comprehensive mapping of tissues vulnerable to neutrophil elastase damage when AAT is deficient.

Bone Marrow and Hematopoiesis

• AAT's role in protecting thrombospondin-1
• Impact on blood cell formation and maturation
• Impact on Multiple Myeloma
• Connection to anemia, thrombocytopenia, and blood disorders
• Neutrophil elastase effects on hematopoietic stem cells
• Bone marrow microenvironment protection

Cardiovascular System

• Endothelial cell protection and vascular health
• Atherosclerosis prevention and plaque stability
• Aneurysm formation prevention
• Cardiac tissue protection
• Microvascular damage in capillaries

Nervous System

• Blood-brain barrier integrity
• Neuronal protection from inflammatory damage
• Relationship to Parkinson's Disease
• Myelin sheath preservation
• Neurotransmitter function
• Synaptic health and cognitive preservation

Connective Tissues

• Cartilage protection in joints
• Skin integrity and wound healing
• Ligament and tendon health
• Bone matrix protection
• Panniculitis and adipose tissue

Renal System

• Glomerular basement membrane protection
• Tubular function preservation
• Prevention of nephropathy
• Renal vasculature protection

Gastrointestinal System

• Intestinal barrier integrity
• Protection against inflammatory bowel disease
• Pancreatic tissue protection
• Hepatic inflammation control

Reproductive System

• Placental function and pregnancy outcomes
• Fertility preservation
• Reproductive tissue protection
• Fetal development impacts

Endocrine System

• Pancreatic islet cell protection
• Thyroid tissue preservation
• Adrenal function
• Hormonal regulation

We will fund:

• Systematic tissue analysis in AAT-deficient animal models
• Human tissue banking and analysis projects
• Proteomic studies identifying AAT-protected proteins
• Single-cell analysis of neutrophil elastase damage
• Longitudinal studies tracking tissue changes over time

Goal: Create a complete atlas of AAT's protective role throughout the human body, identifying all systems that require adequate AAT levels for optimal health.

Funding Focus: Better, faster, more accessible testing methods for AATD.

Research Areas:

• Point-of-care testing devices
• Dried blood spot analysis
• At-home testing kits
• Rapid genotyping methods
• Functional AAT activity assays
• Multiplex testing for AAT and related biomarkers

Goal: Make AATD testing as routine and accessible as cholesterol screening.

Research Questions:

• What is the optimal AAT dose for different conditions?
• Should dosing be adjusted based on inflammatory burden?
• What AAT blood levels achieve maximal protection?
• How frequently should augmentation therapy be administered?
• What combination therapies enhance AAT effectiveness?

We'll fund development of:

• Screening protocols for at-risk populations
• Prevention strategies for carrier states
• Environmental protection guidelines
• Lifestyle modifications enhancing AAT function
• Early intervention protocols for newly diagnosed patients

The Mark Egly Foundation welcomes proposals from:

Academic Researchers

• University laboratories and medical schools
• Research institutes and centers of excellence
• Graduate students and postdoctoral fellows
• Collaborative research networks

Industry Partners

• Large pharmaceutical companies
• Small and medium biotech firms
• Startup companies with innovative approaches
• Medical device manufacturers
• Diagnostic companies

Clinical Researchers

• Physician-scientists conducting patient-centered research
• Multi-center clinical trial networks
• Hospital research departments
• Private practice clinicians with research ideas

Research Spectrum

• Basic Science - Molecular mechanisms and cellular effects
• Translational Research - Bridge from bench to bedside
• Clinical Research - Human studies and trials
• Population Studies - Epidemiology and public health research
• Health Services Research - Access, delivery, and outcomes

Previously Unconsidered Uses of AAT:

Neuropsychiatric Applications

• AAT in depression with inflammatory markers
• Schizophrenia and neuroinflammation
• Autism spectrum disorders
• ADHD with immune dysfunction

Age-Related Conditions

• Inflammaging and healthspan extension
• Frailty prevention
• Sarcopenia (age-related muscle loss)
• Age-related cognitive decline

Infectious Disease

• AAT modulating severe infection responses
• Post-viral syndromes and Long COVID
• Sepsis prevention and treatment
• Vaccine response optimization

Metabolic Disorders

• Non-alcoholic fatty liver disease (NAFLD)
• Metabolic syndrome
• Obesity-related inflammation
• Insulin resistance

Specialized Applications

• Organ transplant rejection prevention
• Graft-versus-host disease
• Surgical recovery enhancement
• Sports injury and recovery
• Cosmetic and dermatological uses

Sound Scientific Rationale

• Clear hypothesis based on established science
• Connection to Mark Egly's discoveries or existing AAT research
• Logical experimental design
• Measurable outcomes

Clinical Relevance

• Potential to improve patient care
• Practical applicability
• Scalability if successful
• Patient-centered outcomes

Research Rigor

• Appropriate controls and statistical power
• Ethical conduct and IRB approval
• Data transparency and sharing
• Peer review and publication commitment

Financial Support

• Grant funding for promising research
• Flexible funding structures
• Multi-year support for complex projects
• Seed funding for pilot studies

Collaborative Network

• Access to "Uniting Doctors" research community
• Patient registries and data resources
• Expertise and consultation
• Publishing and dissemination support

Advocacy and Promotion

• Highlighting important research findings
• Connecting researchers with potential collaborators
• Public awareness of breakthrough discoveries
• Policy advocacy based on research findings

Through strategic research funding, the Mark Egly Foundation aims to:

• Prevent diseases before they cause irreversible damage
• Expand AAT therapy to millions who could benefit
• Reduce healthcare costs through prevention and early intervention
• Improve quality of life for patients with chronic inflammatory conditions
• Revolutionize how medicine understands and treats autoimmune diseases
• Eliminate barriers to AAT access through alternative production
• Save lives by identifying and treating AATD earlier and more comprehensively

Step 1: Review Our Priorities

Ensure your research aligns with our strategic focus areas.

Step 2: Prepare Your Proposal

Include:

• Research question and hypothesis
• Background and significance
• Methods and experimental design
• Expected outcomes and timeline
• Budget and justification
• Your qualifications and team
• Institutional support

Step 3: Submit Your Concept

Contact us through the foundation website or reach out directly with a brief concept paper (2-3 pages).

Step 4: Full Proposal (if invited)

Selected concepts will be invited to submit full proposals for peer review.

Mark Egly spent 45 years searching for answers to his family's tragic health history. His discoveries have opened new horizons in medicine. Now, through research funding, the Mark Egly Foundation continues that mission—supporting scientists and clinicians who will expand these discoveries and transform healthcare for millions.

Together, we will:

• Identify every disease influenced by Alpha-1 Antitrypsin
• Develop prevention strategies for conditions currently considered inevitable
• Make AAT therapy accessible to everyone who needs it
• Change the standard of care across multiple medical specialties
• Save lives and prevent suffering on a global scale

Alpha-1 Antitrypsin research stands at a critical juncture. Mark's discoveries have revealed vast therapeutic potential beyond traditional AATD treatment. Now we need research to prove, expand, and translate these insights into clinical practice.

Your research could be the breakthrough that:

• Prevents cancer metastasis
• Stops autoimmune disease progression
• Protects brain tissue from Alzheimer's
• Makes AAT affordable and accessible worldwide
• Changes medicine's approach to inflammation

For research funding inquiries, collaborative opportunities, or to submit a research proposal, please contact:

The Mark Egly Foundation Research Program

Advancing Alpha-1 Antitrypsin Research for Global Health

Let's discover tomorrow's cures today.