Primary sclerosing cholangitis (PSC)
Chronic cholestatic autoimmune liver disease with intrahepatic + extrahepatic bile duct strictures and beaded MRCP appearance. ~70-80% have concurrent IBD (mostly UC pancolitis with right-sided predominance). 10-15% lifetime cholangiocarcinoma (CCA) risk. Male predominance ~2:1 (opposite of PBC's ~9:1 female). NO DISEASE-MODIFYING THERAPY EXISTS. UDCA at moderate doses (15-20 mg/kg) is contested — may improve biochemistry without progression benefit; high-dose UDCA (28-30 mg/kg) FAILED Lindor 2009 NEJM and STOPPED EARLY for INCREASED serious adverse events + transplant need — the PSC-specific anti-supplement-stacking precedent (analog to Berson 1993 RP vitamin E). Annual MRCP + CA 19-9 for CCA surveillance. Annual colonoscopy when IBD overlap is present (PSC-IBD CRC risk exceeds IBD alone). ERCP for dominant strictures with brushings for CCA. Liver transplant for end-stage (5-year survival 80-85%); ~25% post-transplant recurrence. Trial-enrollment paths: norUDCA Phase 3 (most active DMT candidate); cilofexor FXR agonist failed Phase 2; vancomycin off-label small pediatric studies; vedolizumab for IBD overlap with emerging liver signal; bezafibrate off-label per BEZURSO extrapolation. Pruritus ladder (rifampin → cholestyramine → naltrexone → sertraline). AASLD 2022 + EASL 2022. PSC Partners Seeking a Cure + PSC Support. The editorial honest answer for this trigger is that no peptide in the Juno library has a defensible discovery-card case — trial enrollment is the actionable conversation.
What changes during this transition
PSC is the rare hepatology condition where the load-bearing fact is what doesn't exist: there is no disease-modifying therapy. UDCA — the workhorse for PBC — sits in a genuinely contested place in PSC: moderate doses (15-20 mg/kg) improve biochemistry without clear evidence of progression benefit, and high doses (28-30 mg/kg) were stopped early in the Lindor 2009 NEJM trial after a signal of increased serious adverse events and need for transplant. That harm signal is the PSC-specific anti-supplement-stacking lesson the way Berson 1993 RP vitamin E is for retinitis pigmentosa: well-meaning escalation in a disease without DMT made outcomes worse, not better. The other load-bearing facts that shape every substrate entry. ~70-80% IBD overlap, mostly ulcerative colitis with pancolitis and right-sided predominance — meaning two specialists (hepatology + IBD-focused gastroenterology) are co-managing. 10-15% lifetime cholangiocarcinoma (CCA) risk, with annual MRCP + CA 19-9 the surveillance backbone. Annual colonoscopy when IBD overlap is present (CRC risk in PSC-IBD outpaces IBD alone). ~25% post-transplant recurrence — transplant is definitive for end-stage but not curative-in-the-population sense. Male predominance ~2:1 — the editorial inverse of PBC's ~9:1 female predominance; PSC and PBC are not interchangeable cholestatic diseases. PBC has effective DMT (UDCA + 2024 PPAR agonists elafibranor + seladelpar + obeticholic acid post-September 2024 restriction); PSC does not. The inversion matters for users self-researching cholestatic disease. Trial-enrollment paths matter editorially because they're the actionable conversation. norUDCA (norursodeoxycholic acid) Phase 3 is the live trial-enrollment conversation. Cilofexor (FXR agonist) failed Phase 2. Vancomycin off-label has small pediatric signals. Vedolizumab treats the IBD overlap with some emerging liver signal in small studies. Bezafibrate off-label per BEZURSO extrapolation has been explored. ERCP for dominant strictures with brushings for CCA is the established procedural conversation. Pruritus management ladder: rifampin first-line, then cholestyramine, naltrexone, sertraline. Fat-soluble vitamin (A, D, E, K) repletion for cholestatic malabsorption. DEXA for cholestasis-related osteoporosis. AASLD 2022 + EASL 2022 guidelines anchor management. PSC Partners Seeking a Cure and PSC Support are the major patient organizations. Where Juno's library fits — narrowly and with deliberate non-elevation. PSC is exactly the disease class where peptide enthusiasm is most likely to cause harm — because the absence of DMT creates a vacuum that community claims rush to fill, and the Lindor 2009 high-dose UDCA harm signal proves the vacuum is dangerous to fill cavalierly. The five drafted substrate entries (BPC-157, TB-500, NMN, SS-31, Thymosin alpha-1) exist for honest /ask answers when users probe. BPC-157's 'gut-liver axis' framing via IBD overlap doesn't translate (PSC isn't an IBD subtype with a bile-duct manifestation). TB-500's fibrosis-attenuation extrapolation falls into the same trap as high-dose UDCA — biochemistry can shift without altering disease course, and the Lindor 2009 precedent means iatrogenic harm is non-trivial. NMN's NAFLD-context NAD+ work doesn't transfer to cholestatic disease. SS-31's Barth syndrome FDA approval (March 2025) + AMD + mitochondrial myopathy trial base does NOT propagate per Rule 6, and the cost-benefit asymmetry (expensive, supply-constrained, zero PSC data) makes the calculation worse. Thymosin alpha-1's hepatitis B/C registered indications do NOT propagate to autoimmune cholangiopathy, AND the immune-stimulation profile cuts AGAINST the immune-suppressive considerations PSC management often includes (vedolizumab for IBD overlap, post-transplant immunosuppression, autoimmune-hepatitis-overlap syndrome that some PSC patients carry). The honest editorial frame: hepatology + IBD-gastroenterology co-management, annual MRCP + CA 19-9 + colonoscopy if IBD overlap, ERCP for dominant strictures with CCA brushings, fat-soluble vitamin repletion, DEXA + bisphosphonates for cholestasis-osteoporosis, trial enrollment (norUDCA Phase 3, vedolizumab-for-liver-signal, vancomycin pediatric), AASLD 2022 + EASL 2022 guidelines, and PSC Partners + PSC Support patient organization resources drive outcomes.
Important caveat
PSC is hepatology + IBD-focused gastroenterology co-managed chronic cholestatic autoimmune liver disease — MRCP for biliary tree imaging (beaded appearance characteristic), liver biopsy where useful, ALP / GGT / bilirubin / albumin / INR for staging and synthetic function, IgG4 for IgG4-associated cholangiopathy rule-out, ANCA (often p-ANCA-positive in PSC), MELD-Na for transplant trajectory drive workup. No peptide substitutes for this care framework. THERE IS NO DISEASE-MODIFYING THERAPY for PSC. UDCA at moderate doses (15-20 mg/kg) is contested — may improve biochemistry without clear progression-benefit evidence. HIGH-DOSE UDCA (28-30 mg/kg) WAS STOPPED EARLY in the Lindor 2009 NEJM trial for INCREASED serious adverse events + transplant need — this is the PSC-specific anti-supplement-stacking precedent and the disease-class analog of Berson 1993 RP vitamin E. Trial-enrollment is the actionable path: norUDCA (norursodeoxycholic acid) Phase 3 (most active DMT candidate); cilofexor FXR agonist FAILED Phase 2 (worth knowing because it's the canonical 'FXR pathway didn't deliver' result in PSC); vancomycin off-label small pediatric studies; vedolizumab for IBD overlap with some emerging liver signal; bezafibrate off-label per BEZURSO extrapolation. CCA surveillance: annual MRCP + CA 19-9 (CA 19-9 imperfect; elevation triggers ERCP with brushings); 10-15% lifetime cholangiocarcinoma risk. Annual colonoscopy when IBD overlap (~70-80% of patients, mostly UC pancolitis with right-sided predominance) — PSC-IBD CRC risk exceeds IBD alone. ERCP for dominant strictures (balloon dilation +/- stent; brushings for CCA). Pruritus management ladder: rifampin first-line, then cholestyramine, naltrexone, sertraline. Fat-soluble vitamin (A, D, E, K) repletion for cholestatic malabsorption. DEXA + bisphosphonates for cholestasis-related osteoporosis. Liver transplant for end-stage disease (5-year survival 80-85%); ~25% post-transplant recurrence rate. Male predominance ~2:1 — the editorial INVERSE of PBC's ~9:1 female predominance; PSC and PBC are NOT interchangeable cholestatic diseases (PBC has effective DMT in UDCA + 2024 PPAR agonists elafibranor + seladelpar; PSC has none). AASLD 2022 + EASL 2022 guidelines. PSC Partners Seeking a Cure + PSC Support patient organizations. No Juno library peptide is surfaced as a PSC discovery card. Rule 6 non-propagation: BPC-157's gastric / IBD preclinical corpus does NOT propagate to cholestatic biliary disease; TB-500's fibrosis-attenuation framing falls into the same intervention-without-addressing-upstream-injury trap as high-dose UDCA per Lindor 2009; NMN's NAFLD-context NAD+ work does NOT propagate to cholestatic autoimmune disease; SS-31's Forzinity Barth syndrome FDA approval (March 2025) + AMD ReCLAIM-2 + mitochondrial myopathy trial base does NOT propagate to PSC, and cost-benefit asymmetry is sharp (expensive + supply-constrained + zero PSC data + intervention-harm precedent); Thymosin alpha-1's hepatitis B/C registered indications across multiple non-US jurisdictions do NOT propagate to autoimmune cholangiopathy — the immune-stimulation profile cuts AGAINST the immune-suppressive considerations PSC management often includes (vedolizumab for IBD overlap, post-transplant immunosuppression, autoimmune-hepatitis-overlap syndrome). The Lindor 2009 high-dose UDCA harm signal is the PSC-specific anti-supplement-stacking lesson — escalation in PSC has documented capacity to harm. WADA athletes: BPC-157 (S0) and TB-500 (S2) prohibited at all times. Pregnancy: PSC pregnancies are high-risk and require hepatology + maternal-fetal medicine + IBD-gastroenterology coordination; UDCA generally continued through pregnancy if on it; IBD therapies managed per pregnancy-specific guidance (anti-TNF with certolizumab preferred in third trimester for low placental transfer; vedolizumab and ustekinumab continued with specialist guidance; methotrexate ABSOLUTELY CONTRAINDICATED). Cancer surveillance during pregnancy and post-partum requires modified imaging schedules.
Want this list to grow? The library is editorial — if there’s a peptide you think belongs on this page with documented or mechanistically-clear evidence, send us a note with the citation and we’ll review it under the same evidence-tier discipline as every other entry.