Research ArticlesWorking papers, published research & mechanistic foundations

What the first drug to show clinical improvement in autism's core social symptoms reveals about the IDA cascade — and why it is only part of the answer. A complete mechanistic analysis of the Yamo Pharmaceuticals Phase 2 results (NCT05067582), the Vineland-3 subdomain fingerprint as IDA-confirmatory evidence, long-term risk considerations, and the synergy hypothesis for combination therapy with the IMIG priming protocol and IMIG therapy. Includes the three-state reversibility model, the neuropeptide triad failure analysis, and falsifiable predictions distinguishing combination from monotherapy.

One condition fails to open synaptic plasticity, or keep it open; the other has plasticity closing prematurely later in life. Explores the shared biology of synaptic remodeling failure — hevin/SPARC astrocyte signaling, perineuronal net remodeling, and neuroinflammation as the common mechanism — and what it means for the reversibility of SST-14 interneuron loss described elsewhere in the framework.

Proposes that appetite phenotype in ASD is a surface readout of upstream cytokine dominance — an IFN-γ-dominant, IDO1-active locked cascade (No-Appetite Group) versus a TNF-α-dominant, IDO1-inactive dynamic cascade (Appetite Group). Both converge on NF-κB-mediated SST-14 silencing through mechanistically distinct and differently reversible routes. Includes a full biomarker panel, testable predictions, differential IMIG response trajectories, and an explicit tryptophan/5-HTP contraindication in the AG subgroup.

Using IMIG, IVIG, and MSC therapy as parallel pathways to neuropeptide cascade recovery. Proposes the three-state SST-14 interneuron model, a six-component adjunctive metabolic support framework, and a biomarker-stratified trial architecture with state-assignment decision algorithm and neuropeptide cascade restoration as the primary endpoint. Includes convergent evidence from Naviaux's cell danger response framework and Morrow's GPT2 mitochondrial research as independent proof-of-concept for the State 2 model, a candidate SIRT1/NF-κB supporting mechanism for Mechanism A, and a second IDO1-driven hypothalamic route to oxytocin suppression. Version 19 · 66 references. Companion to The Anatomy of Immune-Derived Autism.

A systems biology dissection of immune-derived autism presenting a two-layer model: the convergent cascade tracing founding conditions through gut pH dysregulation, immune activation, IDO1, and NF-κB to SST-14 interneuron silencing; and a constitutional susceptibility architecture identifying seven tipping points that determine who the cascade propagates in. Includes the three-state clinical framework, the CREB/CBP/CRE transcriptional suppression mechanism, the estrogen-cAMP sex ratio explanation, a parallel viral-reactivation entry point into the immune-activation arm, a second IDO1-driven hypothalamic route to oxytocin suppression, and ten testable predictions. Version 16 · 55 references. Working document — under expert review prior to journal submission.

Twenty-five years of promising autism treatments — secretin, oxytocin, IVIG, suramin, vancomycin, arbaclofen — followed the same arc: compelling mechanism, striking early results, failure at scale. Argues the treatments were not wrong; the trial design and treatment architecture were. Uses the Frye folate-receptor-antibody precedent as proof that biomarker-selected enrollment works, and proposes the three-state SST-14 model as the corrective selection framework. Version 1.0 · 16 references. Companion to Reversing SST-14 Silencing.

A mechanistic framework for SST-14 transcriptional restoration through an eleven-agent, three-phase priming protocol addressing both NF-κB-mediated CREB suppression and adenosine-driven adenylyl cyclase starvation. Framed as a proposed cohort-split trial design comparator arm, with full constitutional susceptibility architecture, the mu-opioid and estrogen-cAMP axis context, and a dedicated scientific-honesty section on what the priming protocol cannot do that IMIG can. Working paper — July 2026 · Version 5.

How Roundup disrupts gut microbiome function, depletes tryptophan availability, and feeds directly into the IDO1 cascade — a mechanistic connection with direct implications for the Biology of Autism framework.

IL-6, IL-17A, and fetal microglial priming. How prenatal immune events establish the inflammatory baseline that persists throughout neurodevelopment and shapes the ASD phenotype.

The CCK/opioid peptide → somatostatin no-off-switch mechanism, the upstream cholinergic suppression arm, and downstream consequences across seven gut peptides. Companion to Chapter 11 of the core framework.

How acetaminophen use around vaccination depletes sulfate availability, disrupts glycosaminoglycan synthesis, and may impair the detoxification capacity needed to clear adjuvant load in susceptible children.

Microbiome differences, lifestyle, vaccine exposure differential, and what lower observed ASD rates in Amish communities do and don't mean for the biological cascade model.

The metabolic mechanism linking estrogen signaling to IDO1 activity, adenylyl cyclase, and the male-to-female ASD population ratio — why the sex difference in ASD prevalence may be hormonally mediated.

What each receptor system does, how E/I imbalance develops, and how the kynurenine pathway and calcium dysregulation drive excitatory overload in the autism cascade.

When pepsin cannot break proline bonds at low pH, casomorphin and gliadorphin peptides remain intact. Which amino acids stay trapped, what opioid-like signaling results, and what this means for tryptophan availability, CCK, and the ASD cascade.

Persistent anti-streptococcal serology without active infection points to molecular mimicry — the immune system attacking self-tissue that resembles strep antigens. How this connects to basal ganglia autoantibodies, PANS, and immune-triggered regression in ASD.