Wilson disease
Wilson disease is an autosomal recessive inherited disorder of copper metabolism caused by biallelic mutations in ATP7B on chromosome 13 — over 700 known pathogenic variants encode a defective copper-transporting ATPase in hepatocytes that cannot excrete copper into bile or load it onto ceruloplasmin. Progressive hepatic copper accumulation with spillover into CNS (basal ganglia + brainstem), cornea (Kayser-Fleischer rings on Descemet's membrane), kidney, and red cell line. Presentations span hepatic (steatohepatitis to cirrhosis to acute liver failure, sometimes as fulminant hepatic failure with Coombs-negative hemolysis), neurologic (tremor, dystonia, parkinsonism, dysarthria, cerebellar signs), psychiatric (depression, personality change, psychosis), and mixed. Diagnostics anchor on serum ceruloplasmin (low <20 mg/dL in ~95%), 24-hour urinary copper (>100 µg, or >40 µg pre-symptomatic), Kayser-Fleischer rings on slit-lamp (~95% of neurologic Wilson, ~50% hepatic), liver biopsy with hepatic copper quantification (>250 µg/g dry weight diagnostic), ATP7B genetic testing, and the Leipzig score. Standard of care: chelation — D-penicillamine, trientine tetrahydrochloride (Cuvrior FDA 2022), zinc salts (zinc acetate Galzin FDA 1997 maintenance gold standard) — plus strict low-copper diet, mandatory family screening of first-degree relatives, and liver transplant for acute liver failure or refractory decompensated disease. AASLD 2023 + EASL 2012 + APASL. No peptide has Wilson-disease evidence. Thirtieth deliberate non-elevation.
What changes during this transition
Wilson disease arrives in the peptide-companion library along three predictable community-curiosity vectors, each of which fails on the same load-bearing reason: the disease is a Mendelian copper-transport disorder, and peptides do not address that. The first vector is the 'liver-healing peptide' register — BPC-157 in particular, and to a lesser extent TB-500 with its anti-fibrotic framing. The community-peptide reflex for any chronic liver disease is to nominate BPC-157, and Wilson disease, with its hepatic presentations spanning steatohepatitis to cirrhosis to acute liver failure, gets pulled into that pattern. The mechanism mismatch is total: BPC-157 does not chelate copper, does not induce metallothionein, does not restore ATP7B function, and does not prevent the hepatic copper accumulation that drives the disease. TB-500's anti-fibrotic framing inverts the altitude — fibrosis in Wilson disease is downstream of unremitting copper-driven hepatocyte injury, and treating fibrosis without chelating copper is mechanically equivalent to mopping a floor with the tap running. The second vector is the 'mitochondrial dysfunction' register — NMN, more sharply SS-31 / elamipretide. Copper toxicity does produce documented mitochondrial dysfunction in hepatocytes and basal ganglia neurons, and this gives the mitochondrial-protection framing more mechanistic coherence than the liver-healing register has. But the framing trap is exactly the same: the upstream load-bearing problem is copper accumulation. Mitochondria recover when copper is removed. Supporting mitochondria while leaving the copper accumulation unaddressed is the 'treat downstream when upstream is the load-bearing problem' trap in its purest form. SS-31's FDA approval (Forzinity, March 2025) is for Barth syndrome — a rare X-linked cardiolipin-remodeling disorder — and Rule 6 blocks propagation. NMN's general-aging biomarker case has no Wilson-disease trial anchor. Critically: copper-containing multivitamins are explicitly contraindicated in Wilson disease, and the supplement-aisle navigation problem this creates is one of the most underdiscussed patient-education traps in the entire disorder. The third vector is the 'neuroprotection' register — Cerebrolysin in particular. The Cerebrolysin multi-jurisdictional clinical register is real and respected — Austrian, German, Russian, Chinese, Mexican, and Romanian groups have published trial work in ischemic stroke, TBI, and vascular dementia. That register does not include Wilson disease. The neurologic Wilson presentation — tremor, dystonia, parkinsonism, dysarthria, cerebellar signs — is mechanistically distinct from the registered indications, and the load-bearing complication of the neurologic Wilson trajectory is paradoxical worsening during chelation initiation (10-50% with penicillamine, less with trientine), which is a chelator-selection conversation, not a neuroprotection-adjunct conversation. What anchors Wilson-disease management is well-defined and has been for decades. Chelation with D-penicillamine (older standard, ~30% adverse-effect rate, paradoxical neurologic worsening in 10-50% of neurologic Wilson during initiation, mandatory pyridoxine co-administration), trientine tetrahydrochloride (Cuvrior FDA 2022; better tolerated than penicillamine), or zinc salts (zinc acetate Galzin FDA 1997 the maintenance gold standard via metallothionein induction in enterocytes; zinc gluconate and zinc sulfate as alternatives; the standard for maintenance, asymptomatic siblings identified through family screening, and pregnancy). A strict low-copper diet — avoiding shellfish, organ meats, mushrooms, nuts, chocolate (cocoa), and unprocessed wheat germ — is patient-education load-bearing. Copper plumbing and copper cookware require testing and substitution. Liver transplant is curative for acute liver failure or refractory decompensation because the donor liver has functioning ATP7B. Family screening of first-degree relatives is mandatory (ATP7B genetic testing + ceruloplasmin + 24-hour urinary copper), because pre-symptomatic siblings identified early can be placed on zinc maintenance and never develop the end-organ damage. The Wilson Therapeutics / Alexion / AstraZeneca WTX-101 (bis-choline tetrathiomolybdate) Phase 3 FoCus trial result was mixed and the drug is not approved, but the molybdate biology continues to inform the ongoing pipeline. Vivet Therapeutics' VTX-801 AAV-mediated ATP7B gene therapy Phase 1/2 GATEWAY trial is actively enrolling, with Ultragenyx and partners running parallel programs — this is a genuinely active gene-therapy frontier where the conversation about disease-modifying intervention has real momentum. The editorial posture across all five substrate entries is the same: peptides are not the conversation in Wilson disease, the hepatology team is the anchor, the chelation regimen is the load-bearing intervention, the low-copper diet and family screening are the patient-education non-negotiables, and the gene-therapy pipeline is where the substantive disease-modifying frontier is moving.
Important caveat
Wilson disease is hepatology-anchored — your hepatologist (and, where relevant, your movement-disorder neurologist, psychiatrist for psychiatric Wilson presentations, ophthalmologist for KF-ring follow-up, and maternal-fetal medicine specialist during pregnancy) leads diagnosis, chelator selection, and surveillance. Diagnosis follows AASLD 2023 / EASL 2012 / APASL guidelines anchored on the Leipzig score, integrating serum ceruloplasmin (low <20 mg/dL in ~95%; can be normal in inflammation), 24-hour urinary copper (>100 µg, or >40 µg in pre-symptomatic), Kayser-Fleischer rings on slit-lamp (~95% neurologic, ~50% hepatic), liver biopsy with hepatic copper quantification (>250 µg/g dry weight diagnostic), ATP7B genetic testing, and MRI for the neurologic presentation. Standard-of-care chelation lives along three options: D-penicillamine (older standard, ~30% adverse-effect rate including rash, proteinuria, lupus-like syndrome, pyridoxine depletion — mandatory B6 co-administration — and paradoxical neurologic worsening in 10-50% of neurologic Wilson patients during initiation); trientine tetrahydrochloride (Cuvrior, FDA 2022 — alternative chelator with better tolerability and lower paradoxical-worsening rate but the complication is still possible); zinc salts (zinc acetate Galzin FDA 1997, zinc gluconate, zinc sulfate — competitively inhibit intestinal copper absorption via metallothionein induction; the maintenance gold standard, the standard for asymptomatic family-screened siblings, and the standard during pregnancy). LOW-COPPER DIET IS LOAD-BEARING: avoid shellfish, liver and other organ meats, mushrooms, nuts, chocolate (cocoa), unprocessed wheat germ; test home water if copper plumbing is present, use distilled water if needed; avoid copper cookware. COPPER-CONTAINING MULTIVITAMINS ARE EXPLICITLY CONTRAINDICATED — check the label on every supplement in your stack, because this is one of the most common supplement-aisle traps in the entire disorder. FAMILY SCREENING IS MANDATORY: every first-degree relative of any Wilson patient needs ATP7B genetic testing + ceruloplasmin + 24-hour urinary copper; pre-symptomatic siblings identified through screening can be placed on zinc maintenance and never develop end-organ damage, and missing this family-medicine action is the regret pattern that haunts Wilson families when a sibling presents in acute liver failure years later. PREGNANCY: Wilson disease pregnancies require CONTINUATION OF CHELATION OR ZINC — do not stop, the risk of acute liver decompensation or hemolytic crisis is real. Penicillamine is generally continued at reduced dose; trientine is continued; zinc is continued unchanged and is often preferred during pregnancy. All Wilson pregnancies should be hepatology + maternal-fetal medicine coordinated from preconception. Liver transplant is curative for acute liver failure presentation (which can include fulminant hepatic failure with Coombs-negative hemolysis as the presenting picture) and for refractory decompensated cirrhosis — the donor liver has functioning ATP7B and the underlying disorder is corrected. The Wilson Disease Association (US), the Mexican Council of Hepatology, and the European Liver Patients Association are legitimate patient-organization first stops. The bis-choline tetrathiomolybdate (WTX-101, Wilson Therapeutics / Alexion / AstraZeneca) FoCus Phase 3 result was mixed and the drug is not approved. The Vivet Therapeutics VTX-801 AAV-mediated ATP7B gene therapy Phase 1/2 GATEWAY trial is actively enrolling — gene therapy is the genuinely active disease-modifying frontier for Wilson disease. None of the peptides discussed in this substrate (BPC-157, TB-500, NMN, SS-31, Cerebrolysin) have controlled trial evidence in Wilson disease in any jurisdiction; all are research-chemical or specialist-prescription sourcing channels with the usual quality-assurance concerns; interaction profiles with D-penicillamine, trientine, and zinc are uncharacterized; and copper-containing supplement contamination during compounded-vendor sourcing is a non-trivial risk that adds an extra layer of concern in this specific disorder. WADA athletes: BPC-157 (S0) and TB-500 (S2) prohibited at all times. This substrate is editorial honesty for /ask probing; it is not a recommendation to use any of these peptides in Wilson disease.
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