Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental allergic encephalomyelitis (EAE) was induced in Buffalo rats by immunization with syngeneic spinal cord homogenate in complete adjuvant. EAE, an autoimmune disease of the central nervous system (CNS), is regarded as a model for multiple sclerosis. When severe paresis had developed, rats were treated with high-dose total body irradiation (TBI) and transplanted with syngeneic BM from healthy donors. Nine Gy TBI followed by syngeneic BMT greatly accelerated recovery of paresis compared with untreated controls. In 6-33% of the treated animals a relapse of EAE was observed shortly after treatment. Reimmunization 20 days after treatment, resulted in a relapse in 12-44% of the rats. Employing the maximally tolerated dose of TBI (10 Gy) did not significantly alter the incidence of spontaneous or induced relapses. Furthermore, it was shown that irradiation of the CNS only was not sufficient for the induction of complete regression of paresis. The origin of the cells responsible for these relapses is discussed, as is the importance of reimmunization in evaluating the effect of treatment of experimental autoimmune disease.
 ...
PMID:Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT. 846 89

We previously showed that relapsing experimental autoimmune encephalomyelitis (R-EAE) in BUF rats, a model for multiple sclerosis, responds favorably to treatment with TBI and syngeneic BMT. Relapses of paresis occurred less frequently than in untreated controls, but were not completely prevented. Therefore, we investigated the effect of allogeneic BMT from the resistant WAG rat strain. BUF rats were treated with either high-dose TBI or CY and Bu followed by allogeneic BMT. This treatment induced complete remission, and reduced both the spontaneous and induced relapse rate more efficaciously than syngeneic BMT. Evidence is provided that a subclinical GVHR contributes to the prevention of spontaneous relapses. The almost complete absence of induced relapses likely results from the repopulation by the resistant immune system of the donor, which proved to be functional by responding to immunization with type II collagen. It is thus unlikely that a BMT-related immunodepression contributed to the lower incidence of induced relapses. We propose that allogeneic BMT should be considered for the treatment of severe progressive MS with a poor prognosis.
 ...
PMID:Treatment of relapsing experimental autoimmune encephalomyelitis in rats with allogeneic bone marrow transplantation from a resistant strain. 853 5

BUF rats suffering from severe relapsing experimental autoimmune encephalomyelitis (R-EAE), a model for multiple sclerosis, were treated with intensive cytoreductive therapy and grafting of allogeneic bone marrow (BM). BN.1B rats were used as EAE-resistant, largely MHC-matched donors, resembling human BMT from HLA-identical siblings. The treatment induces complete remission and low recurrence rates of R-EAE. Evidence is provided that the efficacy of the treatment depends on a high degree of lymphoablation: a minority of rats had host-type residual activated T lymphocytes in the CNS after treatment. Furthermore, complete replacement of host-type BM by donor-type hemopoietic cells is essential, as higher relapse rates were observed in animals with incomplete reconstitution by donor cells than in completely reconstituted rats. Overall, our results indicate that patients with severe MS might benefit from treatment with HLA-matched allogeneic BM.
 ...
PMID:Treatment of relapsing experimental autoimmune encephalomyelitis with largely MHC-matched allogeneic bone marrow transplantation. 882 82

Several human and experimental autoimmune diseases, including the current model for multiple sclerosis (MS), ie relapsing experimental autoimmune encephalomyelitis (R-EAE), have been reported to respond with complete remission to lympho- and myeloablation and rescue with transplantation of bone marrow (BMT) from healthy donors. Since treatment with autologous BM was as effective in our arthritis model as treatment with allogeneic BM from healthy rats, and in view of the much lower risk of autologous BMT in clinical practice, we have investigated treatment of R-EAE with pseudo-autologous (PSA) BM. PSABM is harvested from animals in the same active stage of R-EAE as the syngeneic recipients which are to be treated. Our results show that PSABM is as effective as syngeneic BM, except for a higher incidence of artificially induced relapses. We also demonstrated that lymphocytes present in the autologous BM graft may contribute to the occurrence of relapses post-transplantation. The implications of our results for a possible clinical application in the treatment of MS patients are discussed. If such treatment is envisaged, the use of T cell-depleted autografts seems mandatory, particularly as human BM contains 10 times more lymphocytes than rat BM.
 ...
PMID:Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation. 897 69

Several experimental autoimmune diseases (AID), including allergic encephalomyelitis, ie the multiple sclerosis (MS) model, respond to TBI and chemotherapy followed by BMT. Remissions of AID may also occur in patients with concomitant malignancies treated with allogeneic or autologous BMT. These observations have emphasized the possibility of treating AID with high-dose therapy and haematopoietic stem cell transplantation (HSCT). In a phase I/II pilot study, 15 patients with progressive MS were treated with BEAM followed by autologous blood SCT and antithymocyte globulin (ATG). Patients were severely disabled, with median EDSS and SNRS scores of 6 (5-7.5) and 42 (33-62), respectively. Cyclophosphamide (4 g/m2) and G/GM-CSF (5 microg/kg/day) were used for stem cell mobilization, which caused no neurotoxicity. On days +1 and +2, ATG (2.5-5 mg/kg) was given for in vivo T cell-depletion. Allergy (93%) and infections (87%) were the principal toxic complications. Mild, transient, neurotoxicity was observed in six patients in the immediate post-transplant period. The median follow-up time is 6 months (6-18). Durable neurologic improvements have been detected on both the EDSS (7/15) and SNRS (15/15) systems. One patient worsened at 3 months and two have relapsed. Autologous HSCT appears feasible in MS; it does not aggravate disability and seems to offer a clinical benefit. However, these observations need confirmation and long-term outcomes will show if benefits counterbalance toxicity and cost.
 ...
PMID:Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. 938 25

Relapsing experimental autoimmune encephalomyelitis (R-EAE) is an immune-mediated demyelinating central nervous system (CNS) disease. Myeloablation and syngeneic bone marrow transplantation (SBMT), when performed at the peak of acute disease (day 14), prevented glial scarring and ameliorated the disease severity. In contrast, when syngeneic BMT was performed late in chronic phase (day 78), significant glial scarring remained and the clinical severity did not differ significantly from that of the controls. After SBMT in either the acute or chronic phase of disease, the posttransplant immune system remained responsive to myelin epitopes as determined by in vitro proliferation and interferon-gamma (IFN-gamma) production. However, in mice undergoing SBMT, in vivo delayed-type hypersensitivity (DTH) responses were significantly decreased while IFN-gamma RNA levels and inflammatory infiltrates within the CNS were slightly improved. We conclude that failure of SBMT to improve the clinical disease when performed in chronic phase may be due to preexisting glial scarring. We also conclude that in the absence of glial scarring and irreversible neuronal injury, in vivo DTH responses and histology are better predictors of clinical improvement than in vitro proliferation or IFN-gamma cytokine production.
 ...
PMID:Effect of disease stage on clinical outcome after syngeneic bone marrow transplantation for relapsing experimental autoimmune encephalomyelitis. 951 63

Since Morton and Siegel's epochal experiments 30 years ago animal models have been successfully utilized both for transfer and resolution of autoimmune diseases (AID). More recently human lymphocyte xenografts have reproduced clinical AID in SCID mice. Allogeneic stem cell transplantation demonstrated therapeutic potential in fully developed autoimmune disease. Mixed allogeneic chimerism induced by a sublethal approach has also been shown to prevent and even reverse autoimmune insulitis in nonobese diabetic (NOD) mice. More unexpectedly it was found that experimental adjuvant arthritis (AA) and experimental allergic encephalomyelitis (EAE) could be cured by means of total body irradiation (TBI) followed by autologous hemolymphopoietic stem cell (HSC) transplantation. It was postulated that the newly developing T cells might be tolerant to self antigens. The transfer of AID from affected donors to recipients of allogeneic HSC transplants has been reported for many organ-specific AID, including diabetes (IDDM), thyroiditis, myasthenia gravis and thrombocytopenic purpura (AITP); rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were not transferred. Conversely patients with the combination of AID and a severe blood disease (leukemia, aplasia) were cured of both diseases following allogeneic BMT, with the notable exception of a relapse in a patient with RA despite full donor engraftment. Allogeneic transplants are certainly more promising as far as concerns a resolution of AID, because they may also exert a graft-versus-autoimmunity effect by gradually eradicating the recipient's lymphopoiesis, but transplant related mortality (TRM) is considered still too high to employ this procedure consistently. New non-myeloablative conditioning regimens, designed to allow the donor's immune system to take over, are already utilized for malignant and non-malignant hematologic diseases, and may become an attractive option for severe, refractory AID. For the time being, however, autologous procedures are still safer, and are being utilized in many projects worldwide. The EBMT/EULAR Registry has collected over 70 patient reports. The more numerous and favorable results have been obtained up to now in multiple scleosis and in systemic lupus erythematosus; the worst in refractory autoimmune thrombocytopenic purpura. No definite conclusions as to the efficacy of autologous HSC transplantation, from marrow or from blood, with or without T-cell depletion, may be drawn at this time, but the feeling is that real cures will be very difficult to obtain by this approach, and that corticosteroid-free remissions and a general lowering of the autoimmune potential will be more realistic goals. Accurate comparisons with already existing aggressive immunosuppressive protocols will become necessary, if possible by means of prospective randomized clinical studies.
 ...
PMID:Stem cell transplantation for severe autoimmune diseases: progress and problems. 979 58