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Chinese Herbal Medicine for Peanut/Food Allergy

Chinese Herbal Medicine for Peanut/Food Allergy. Julie Wang, MD Mount Sinai School of Medicine New York, NY. October 21, 2012. Learning objectives. Discuss the effects of Traditional Chinese Medicine (FAHF-2) in a murine model of food allergy

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Chinese Herbal Medicine for Peanut/Food Allergy

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  1. Chinese Herbal Medicine for Peanut/Food Allergy Julie Wang, MD Mount Sinai School of Medicine New York, NY October 21, 2012

  2. Learning objectives • Discuss the effects of Traditional Chinese Medicine (FAHF-2) in a murine model of food allergy • Describe recent clinical trials using FAHF-2 for food allergic patients

  3. Traditional Chinese Medicine (TCM) • Used in China to treat diseases for thousands of years. • Used as monotherapy or in combination with standard Western medical treatment. • Complex interactions produce synergistic effects and reduce possible side effects. • Given its reputed effectiveness, low cost, and favorable safety profile, TCM is attracting interest in Western countries as a source of alternative or complementary therapy for a variety of diseases, including allergies and asthma.

  4. Development of FAHF-2 • Food allergy has not been described in TCM literature. • Studies of Wu-Mei Wan (10 herbs) on various diseases including gastroenteritis and asthma. No adverse effects in these clinical studies. • Ling Zhi was added enhance to its anti-allergy and anti-inflammatory properties  FAHF-1 • 2 herbs, Xi-Xin and Zhi-Fu-Zi, were eliminated due to potential toxicity if processed improperly. • This refined formula has been named FAHF-2

  5. Traditional Chinese Medicine: FAHF-2 Wu–Mei Huan–Jiao Dang–Gui Gang–Jiang Gui–Zhi Huang–Bai HPLC fingerprint of FAHF- 2 at 254 nm Ling–Zhi Huang–Lian Hong–Shen

  6. FAHF-2: Pre-clinical studies Srivastava K et al. J Allergy Clin Immunol 2009; 123:443-451

  7. Persistent effects of FAHF-2: Symptom scores post PN challenge 5 W14 W18 W22 W28 Early Treatment 4 3 Late Treatment 2 1 *** *** *** *** Symptom Score 0 5 W50 W66 W34 W40 *** ***, P<0.001 vs Sham 4 3 *** 2 1 *** *** 0 Naive Naive Naive Naive Sham Sham Sham Sham FAHF-2 FAHF-2 FAHF-2 FAHF-2

  8. Effects on IgE and IgG2a Figure 3 – Srivastava 2009 Srivastava K et al. J Allergy Clin Immunol 2009; 123:443-451

  9. FAHF-2: Persistent effects on cytokines (Week 50 Post-therapy) Mesenteric lymph node Spleen 1600 1600 1800 1800 Sham Sham 1600 1600 1400 1400 FAHF-2 FAHF-2 * Naive Naive * 1400 1400 1200 1200 * * * 1200 1200 1000 1000 * 1000 1000 Pg/ml Pg/ml Pg/ml Pg/ml 800 800 800 800 * * 600 600 * * 600 600 * * * * * * 400 400 * 400 400 * * * 200 200 200 200 * * * 0 0 0 0 IFN- TGF-β IL IL - - 4 4 IL-5 IL IL - - 13 13 IL IL - - 10 10 IL IL - - 4 4 IL IL - - 5 5 IL IL - - 13 13 IFN- IFN - - IL IL - - 10 10 TGF-β TGF - - * * Srivastava K et al. J Allergy Clin Immunol 2009; 123:443-451

  10. Safety profile of FAHF-2 • Mice fed 24x the effective daily dose • No signs of acute toxicity • No evidence of abnormal liver and kidney functions, abnormal CBC • Normal histology of the major organs Srivastava K et al. J Allergy Clin Immunol 2005; 115:171-178

  11. Synergistic effects of the herbs Kattan J et al. Phytother Res 2008; 22:651-9

  12. Mast cell and basophil effects • Reduction in number of peripheral blood basophils and peritoneal mast cells • Suppression of IgE-mediated mast cell activation Song Y et al. J Allergy Clin Immunol 2010; 126:1208-1217

  13. Multiple food allergies Insert Fig 5 Srivastava K et al. Ann Allergy Asthma Immunol 2012; 108:351-358

  14. Multiple food allergies • No allergic reactions seen at the post-treatment challenges for peanut, codfish, and egg Insert Fig 3 Srivastava K et al. Ann Allergy Asthma Immunol 2012; 108:351-358

  15. Multiple food allergies • Additional findings: • Decreased allergen-stimulated IL-4 and IL-13 production • Increased IFN-g in cultured splenocytes and mesenteric lymph node cells Insert Fig 5 Srivastava K et al. Ann Allergy Asthma Immunol 2012; 108:351-358

  16. FAHF-2: Clinical trials • FDA approval as an investigational new drug IND 77,468 – 2007 • Phase I clinical trial • Study Subjects: 12 – 45 years of age • Documented peanut, tree nut, fish and/or shellfish allergy (positive skin test and/or IgE)

  17. Acute Phase I trial • Double-blind, placebo-controlled, dose escalation trial • 4, 6, 12 tablets TID x 7 days • 18 subjects • No significant adverse effects Wang J et al. Ann Allergy Asthma Immunol 2010; 105:75-84

  18. Acute Phase I – immunologic changes Ex vivo effect of FAHF-2 on cytokine levels in PBMC cultures pre and post FAHF-2 treatment Wang J et al. Ann Allergy Asthma Immunol 2010; 105:75-84

  19. Extended Phase I trial • Open label • 6 tablets TID x 6 months • 18 subjects enrolled, 14 completed treatment • Well-tolerated, no significant adverse effects Patil S et al. J Allergy Clin Immunol 2011; 128:1259-1265.

  20. Extended Phase I immunologic changes P=0.067 P=0.08 Patil S et al. J Allergy Clin Immunol 2011; 128:1259-1265.

  21. Phase II trial: on-going • Double-blind, placebo-controlled • 12-45 years of age • Inclusion: allergy to peanut, tree nut, sesame, fish or shellfish • Therapy: 10 tablets TID x 6 months • Multi-center trial • Mount Sinai School of Medicine, NY • Arkansas Children’s Hospital, AK • Children’s Memorial Hospital, IL

  22. Phase II trial: on-going • Outcomes: • compare threshold for reaction during oral food challenge pre- and post-treatment • prick skin tests • allergen-specific IgE & IgG4 • epitope recognition using peptide microarray • basophil activation • T cell activity

  23. Refined FAHF-2 • A major drawback of the current FAHF-2 formula is the high daily dose • Therefore, a refined FAHF-2 using butanol purification has been developed • B-FAHF-2 at ~1/5 the dose of FAHF-2 resulted in protection from peanut anaphylaxis in the murine model that persisted for 6 months • The beneficial effects could be re-established with a second treatment course • Furthermore, the safety profile and immunologic are similar to FAHF-2

  24. B-FAHF-2: clinical effects Srivastava K et al. Clin Exp Allergy 2011; 41:582-91.

  25. B-FAHF-2: decreased IgEand increased IgG2a IgE IgG2a Srivastava K et al. Clin Exp Allergy 2011; 41:582-91.

  26. B-FAHF-2: immunologic effects Srivastava K et al. Clin Exp Allergy 2011; 41:582-91.

  27. Conclusions • FAHF-2 treatment in peanut allergic mice results in protection from peanut-induced anaphylaxis that persists for ~6 months. • Associated with decreased IgE, increased IgG2a, decreased Th2 cytokines, increased IFN-g • High safety profile • Phase I clinical trial demonstrated safety of FAHF-2 in food allergic individuals • Phase II study investigating efficacy is on-going • B-FAHF-2 achieves similar efficacy and safety at a reduced dose

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