The Glass Cannon Project¶
A patient-and-family–led research effort to characterize heterozygous SAMHD1 p.A565T — a single-copy variant that appears to tune the innate immune system for maximum antiviral offense at the cost of long-term structural and metabolic durability.
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The variant
SAMHD1 c.1693G>A (p.Ala565Thr): one impaired copy of a master nucleotide-metabolism and innate-immune checkpoint enzyme.
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The kindred
A multi-generation carrier family whose living pedigree spans the full human lifespan — a natural history "time machine" for the variant.
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The objectives
Confirm the mechanism, publish the first heterozygous case series, and open a path to treatment and eventual gene correction.
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Weekly research surveillance
An automated semantic sweep of the world's literature, scored against this exact phenotype and published here every week.
Why "glass cannon"?¶
Most disease variants make a protein do less and leave you simply weaker. This one appears to do something stranger. A single impaired copy of SAMHD1 seems to leave the immune system in a permanently primed, aggressive antiviral state — a real biological advantage against infection, and possibly even against early-pregnancy loss. That is the cannon.
The cost is fragility. Under a hard enough hit — an acute viral infection, a metabolic or toxic stressor — the same over-tuned system appears to crash into a self-sustaining inflammatory and bioenergetic failure state it cannot climb back out of: post-viral fatigue (ME/CFS), a chronic interferon signature, progressive immune-cell decline, connective-tissue failure, and diet-resistant metabolic disease. That is the glass.
The Glass Cannon Project exists to prove that model rigorously, to support the families who carry the variant, and to turn the mechanism into treatment.
Status: working framework, not yet peer-reviewed
The "glass cannon" model is a research hypothesis under active investigation. Nothing on this site is medical advice, and specific mechanistic claims are flagged throughout as established, hypothesized, or predicted so readers can tell them apart.
Get involved¶
If you are a clinician, researcher, or a family that carries a SAMHD1 variant and any of this sounds familiar, we would like to hear from you. Contact details and the current call for collaborators live on the Foundation page.