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The Glass Cannon Foundation

First draft

This page is an early draft of the Foundation's framing, published for comment. The "glass cannon" model is a working research hypothesis, not yet peer-reviewed. Wording, scope, and structure are expected to change.

Mission

To characterize heterozygous SAMHD1-driven disease, support the families who carry these variants, and accelerate the path from mechanism to treatment to cure — so that a rare, invisible, multi-system condition becomes recognized, diagnosable, and ultimately correctable.

The problem we exist to solve

People carrying a single impaired copy of SAMHD1 can spend decades being diagnosed one symptom at a time — post-viral fatigue here, an inflammatory arthritis there, unexplained metabolic disease, connective-tissue failures, immune decline — without anyone connecting them to a single upstream cause. Because the heterozygous phenotype has never been formally described, there is no name for it, no diagnostic pattern to match against, and no mechanism-matched treatment plan.

The Glass Cannon Foundation exists to close that gap.

What we mean by "glass cannon"

The name captures the variant's dual character:

  • The cannon — a single impaired copy appears to leave the innate immune system in a permanently primed, aggressive antiviral state. In evolutionary terms this may even be advantageous, which could explain why the variant persists.
  • The glass — that same over-tuned system appears structurally fragile. Under a sufficient stressor it can crash into a self-sustaining inflammatory and bioenergetic failure state, sacrificing metabolic and structural durability for immune gain.

It is, in short, a systems optimization failure — tuned for maximum offense at the cost of resilience.

Objectives

  1. Recognition — publish the first heterozygous SAMHD1 case series and establish the phenotype in the medical literature.
  2. Mechanism — fund and coordinate the confirmatory biology (interferon scoring, primary-cell work, structural modeling).
  3. Family support — provide carrier families with a de-identified, understandable account of the condition and a route to research-grade surveillance of the field.
  4. Treatment — advance a rational, multi-arm therapeutic strategy that addresses both the interferon arm and the JAK-resistant metabolic arm.
  5. Cure — track and, ultimately, help enable precise gene correction of the underlying variant.

Guiding principles

  • Privacy first. Patient and family identities are never published. A technical privacy guard sits at the boundary between our private records and anything public.
  • Honesty about certainty. We label claims as established, hypothesized, or predicted, and we do not overstate. The model is a scaffold for investigation, not a settled fact.
  • Open by default. Our literature surveillance and synthesis are published openly so that other families, clinicians, and researchers benefit.

Get involved

We would like to hear from:

  • Families carrying any SAMHD1 variant who recognize this pattern.
  • Clinicians — rheumatology, immunology, neurology, hepatology, metabolic medicine — who have seen unexplained multi-system cases.
  • Researchers in interferonopathy, mitochondrial biology, nucleotide metabolism, and precision gene editing.

A contact address and formal call for collaborators will be added here. In the meantime, the research blog is updated weekly and is the best window into the current state of the science.