Inflamed Muscle and Innovative Targeted Therapies (MITIC)
Inflamed Muscle and Innovative Targeted TherapiesInflamed Muscle and Innovative Targeted Therapies
Myopathie Inflammatoire et Thérapie Innovante Ciblée (MITIC) is a new research structure, directed by Olivier Benveniste, devoted to translational research as a global aim and focused in the studies of auto immune disease, especially myositis.
Idiopathic inflammatory myopathies are a heterogeneous group of different diseases, classified into four main categories: dermatomyositis, polymyositis which frequently overlap other connective tissue diseases, immune-mediated necrotizing myopathy, and sporadic inclusion body myositis. Polymyositis presents itself with endomysial inflammatory cell infiltrates (rich in CD8+ T-cells) surrounding and invading non-necrotic muscle fibres, in parallel with a diffuse major histocompatibility class I overexpression. The treatment of polymyositis consists of corticosteroids frequently associated with other immunosuppressive drugs. The unavoidable and often severe side effects of these drugs, which have to be taken for several months or years, prompted us to propose alternative treatments, which were tested in experimental animal models.
We have developed a reproducible experimental autoimmune myositis (EAM) model of polymyositis, in which mice are immunized once a week for 3 weeks with 1 mg of partially purified myosin emulsified in complete Freund’s adjuvant. We further demonstrated that it was possible to induce the disease by adoptive transfer of unsorted lymph node cells. In this EAM model, we also demonstrated that administration of regulatory T cells (Tregs) can ameliorate the disease phenotype.
Rapamycin is a well known immunosupressive dugs used for a decade in transplant patients to prevent graft rejection. In vivo, rapamycin has been described to increase the percentage of Tregs. Under preventive or curative treatment in EAM model, an increase of muscle strength was observed with in parallel a decrease of muscle inflammation. Those observations suggest that rapamycin may represent an effective new therapeutic approach in patients with PM, allowing reducing steroid administration. This approach may be particularly beneficial in this patient population, as a deficiency in Treg frequency has been reported in individuals affected by PM.
Now, in this model we study the role of intravenous immunoglobulin (IgIV) and Trisenox (arsenic trioxide).
We also study necrotizing myopathies (with autoantibodies) through myoblast cultures to understand the mechanism that allows the destruction of muscle fibers.
Fields of interest
Contact infoAddress: MITIC U974, 3ème étage, 105 Boulevard de l’Hôpital CHU Pitié-Salpetrière
Postal code: 75651
Telephone: +33 1 40 77 96 84
Fax: +33 1 40 77 81 29
- Prevel N, Allenbach Y, Klatzmann D, Salomon B, Benveniste O.
Beneficial role of rapamycin in experimental autoimmune myositis
PLoS One. 2013 Nov 12;8(11):e74450.
- Terrier B, Geri G, Chaara W, Allenbach Y, Rosenzwajg M, Costedoat-Chalumeau N, Fouret P, Musset L, Benveniste O, Six A, Klatzmann D, Saadoun D, Cacoub P
Interleukin-21 modulates Th1 and Th17 responses in giant cell arteritis
Arthritis Rheum. 2012 Jun;64(6):2001-11.
- Herson S, Hentati F, Rigolet A, Behin A, Romero NB, Leturcq F, Laforêt P, Maisonobe T, Amouri R, Haddad H, Audit M, Montus M, Masurier C, Gjata B, Georger C, Cheraï M, Carlier P, Hogrel JY, Herson A, Allenbach Y, Lemoine FM, Klatzmann D, Sweeney HL et al.
A phase I trial of adeno-associated virus serotype 1-γ-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C
Brain. 135(Pt 2), 483-492 (2012)
- Benveniste O, Guiguet M, Freebody J, Dubourg O, Squier W, Maisonobe T, Stojkovic T, Leite MI, Allenbach Y, Herson S, Brady S, Eymard B, Hilton-Jones D
Long-term observational study of sporadic inclusion body myositis
Brain. 2011 Nov;134(Pt 11):3176-84.
- Benveniste O, Drouot L, Jouen F, Charuel JL, Bloch-Queyrat C, Behin A, Amoura Z, Marie I, Guiguet M, Eymard B, Gilbert D, Tron F, Herson S, Musset L, Boyer O.
Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy.
Arthritis Rheum. 2011 Jul;63(7):1961-71.
- Clement A, Nathan N, Epaud R, Fauroux B and Corvol H.
Interstitial lung diseases in children.
Orphanet J Rare Dis. 2010 Aug 20;5:22.
Preclinical Studies Aimed at Clinical Development
- Allenbach Y, Solly S, Grégoire S, Dubourg O, Salomon B, Butler-Browne G, Musset L, Herson S, Klatzmann D, Benveniste O
Role of regulatory T cells in a new mouse model of experimental autoimmune myositis
Am J Path. 2009, 174:989-98.