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1996 Clinical Trials of
Multiple Sclerosis Therapies


1 The effects of Amantadine and Pemoline on Cognitive Functioning in MS
2 Treatment of Chronic Progressive MS with Cladribine
3 Interferon-ß Inhibits Progression of Relapsing/Remitting Experimental AutoImmune EncephaloMyelitis
4 Glial Cell Transplantation and ReMyelination of the CNS
5 Copolymer-1 Inhibits Chronic Relapsing Experimental Allergic EncephaloMyelitis Induced by Proteolipid Protein (PLP) Peptides in Mice & Interferes with PLP-Specific T-Cell Responses
6 Intravenous Immune Globulin in Multiple Sclerosis: Clinical, Neuroradiological Results & Implications for Possible Mechanisms of Action
7 Oral IFN-alpha: Superior to Subcutaneous IFN-alpha in the Suppression of Chronic Relapsing Experimental AutoImmune EncephaloMyelitis (EAE)
8 A Comparison of two Neurologic Scoring Instruments for Multiple Sclerosis
9 Acyclovir Treatment of R/R Multiple Sclerosis: A Randomized, Placebo-Controlled, Double-Blind Study
10 Functional & NeuroPhysiological Evidence of the Efficacy of Trophic Pharmacotherapy using AdrenoCorticoTrophic Hormone Analog in Experimental Allergic EncephaloMyelitis
11 Cell-Cell Interactions During the Migration of Myelin-Forming Cells Transplanted in the DeMyelinated Spinal Cord
12 Pentoxifylline, a Phosphodiesterase Inhibitor: Induces Immune Deviation in Multiple Sclerosis
13 Impact of Aerobic Training on Fitness & Quality of Life in MS
14 Safety Profile of Copolymer-1 (Copaxone):
Cumulative Experience in United States Israel
15 ImmunoGlobulins Reactive with Myelin Basic Protein - Promote CNS ReMyelination
16 Side Effect Profile of Interferon-ß-1b in MS: Results of an Open Label Trial
17 Subcutaneously Insulin-like Growth Factor-I Reduces Clinical Deficits, Decreases Lesion Severity & Upregulates Synthesis of Myelin Proteins in Experimental AutoImmune EncephaloMyelitis
18 Intramuscular Interferon-ß-1alpha for Disease Progression in Relapsing/Rimitting Multiple Sclerosis
19 Comparative Effects of Interferon-Consensus: Interferon alpha(2a), and Interferon-ß(1b), on HLA Expression & Lymphoproliferation: A Preclinical Model for Treatment of MS
20 Selective Depletion of Myelin-Reactive T-Cells with the Anti-OX-40 Antibody Ameliorates AutoImmune EncephaloMyelitis
21 Intravenous Antigen Administration as Therapy for AutoImmune DeMyelinating Disease



1) The Effects of Amantadine and Pemoline on Cognitive Functioning in Multiple Sclerosis

Summary: The fatigue found in MS patients has been frequently treated by two drugs Amantadine Hydrochloride and Pemoline. These drugs may also improve attention and other Cognitive functions.

This study evaluated the effect of these drugs on Cognitive functioning in MS patients using placebo controlled trials. A total of 45 ambulatory MS patients were treated for 6 weeks with either Amantadine, Pemoline, or a placebo.

The results indicated that Cognitive functioning in MS is NOT related to fatigue and neither Amantadine nor Pemoline enhanced Cognitive performance in MS patients.

MW Geisler, M Sliwinski, PK Coyle, DM Masur, C Doscher, LB Krupp
Archives of Neurology 53: 2 (FEB 1996) Page(s) 185-188
LB Krupp, SUNY Stony Brook, Sch Med, Dept Neurol, Stony Brook, NY 11794 USA



2) Treatment of Chronic Progressive MS with Cladribine

Summary: The authors describe a two year study, initiated in 1992, to evaluate Cladribine (an Immunosupressive drug) in the treatment of Chronic/Progressive MS.

There were positive results obtained in the neurological performance scores (using both Kurtze and Scripps rating scales) and on Magnetic Resonance Imaging (MRI) in patients treated with Cladribine compared to the control patients.

While clinical deterioration continued over the first year in placebo control patients (which were switched onto the drug in the second year of the study) patients receiving Cladribine stabilized or even improved slightly.

Finally, the therapeutic response and the toxic effects of the drug were both dose-related.

E Beutler, JC Sipe, JS Romine, JA Koziol, R Mcmillan, J Zyroff
Proceedings of the National Academy of Sciences of the United States of America 93: 4 (FEB 20 1996) Page(s) 1716-1720
 E Beutler, Scripps Clin & Res Inst, Dept Molec & Exptl Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA



3) Interferon-ß Inhibits Progression of Relapsing/Remitting Experimental AutoImmune EncephaloMyelitis

Summary: Relapsing/Remitting MS has recently been shown in clinical trials to be effectively treated with Interferon-beta (ß).

ß treatment significantly decreased the rate of clinical relapse and showed a considerable delay in the disease progression compared to placebo controls.

In this study, the authors show similar therapeutic benefits after treating mice with ß at the beginning of Experimental AutoImmune EncephaloMyelitis (EAE).

This disease is an animal model widely used in MS studies. In blinded studies (the scientists did not know which mice were treated with ß or a plecebo), a delay in progression to disability was observed in mice treated with ß at EAE onset when compared to placebo control mice.

The ß treated mice had an overall decrease in both inflammation and DeMyelination in the Central Nervous System.

These findings mimic the effectiveness of ß treatment observed in trials with MS patients.

In addition, these findings suggest that the anti-viral properties of ß are not essential for producing these effects.

The mode of action of ß in the treatment of MS may be due to the inhibition of the AutoImmune effect.

M Yu, A Nishiyama, BD Trapp, VK Tuohy
Journal of NeuroImmunology 64: 1 (JAN 1996) Page(s) 91-100
VK Tuohy, Cleveland Clin Fdn, Res Inst, Dept Immunol, FFB-1, 9500 Euclid Ave, Cleveland, OH 44195 USA



4) Glial Cell Transplantation and ReMyelination of the Central Nervous System

Summary: This is a review article discussing the feasibility of using transplantation as a therapy for ReMyelination. The transplantation of Myelin producing Glial cells into the Central Nervous System (CNS) of animals with Myelin damage has raised the possibility that this technique may one day be used as therapy for MS.

New advances in the growth of these cells in tissue culture (outside the body) and a better understanding of the different stages of cell growth and development makes transplantation of these cells attractive.

However, the tissue cultured cells must be carefully monitored to make sure they are not harboring any other Viruses or have not turned Cancerous.

For this technique to be used in humans there must be proof that the ReMyelination will occur in the presence of the existing Nerve damage and inflammation associated with MS.

ID Duncan
Neuropathology and Applied NeuroBiology 22: 2 (APR 1996) Page(s) 87-100
 ID Duncan,
Univ Wisconsin, Sch Vet Med, Dept Med Sci, 2015 Linden Dr W, Madison, WI 53706 USA


5) Copolymer-1 Inhibits Chronic Relapsing Experimental Allergic EncephaloMyelitis Induced by Proteolipid Protein (PLP) Peptides in Mice & Interferes with PLP-Specific T-Cell Responses

Summary: Experimental Allergic EncephaloMyelitis (EAE) is a disease in rodents that is similar to MS in humans.

An Amino Acid copolymer called Copolymer 1 (Cop 1) has been developed to suppress the EAE disease and is a candidate drug for MS treatment. In this study mice injected with the components to induce the EAE disease were also injected with Cop 1.

These mice were almost completely resistant to disease induction. These results support the theory that Cop 1 could be used as a general broad-spectrum drug for MS patients.

D Teitelbaum, M Fridkishareli, R Arnon, M Sela
Journal of NeuroImmunology 64: 2 (FEB 1996) Page(s) 209-217
 M Sela, Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel



6) Intravenous Immune Globulin in Multiple Sclerosis: Clinical, Neuroradiological Results & Implications for Possible Mechanisms of Action

Summary: There have been a number of scientific publications recently reporting on the positive effects of Intravenous Immune Globulin (IVIG) on MS.

IVIG seems to limit inflammation and enhance ReMyelination. In this study the impact of IVIG on arresting the progression of Relapsing/Remitting MS was studied.

People (ages 20-55 years) having MS between 2 and 10 years with a frequency of exacerbations 1-3 per year were selected for the study.

The results of the study appear promising with the reduction in lesion size as measured by Magnetic Resonance Imaging.

A Achiron, Y Barak, M Goren, U Gabbay, S Miron, Z Rotstein, S Noy, I Sarovapinhas
Clinical and Experimental Immunology 104: Suppl. 1 (MAY 1996) Page(s) 67-70
A Achiron, Chaim Sheba Med Ctr, Multiple Sclerosis Ctr, IL-52621 Tel Hashomer, Israel



7) Oral Administration of IFN-alpha: Superior to Subcutaneous Administration of IFN-alpha in the Suppression of Chronic Relapsing Experimental AutoImmune EncephaloMyelitis (EAE)

Summary: Interferon-alpha (IFN) is a naturally occurring chemical that has regulatory effects on some cells of the immune system.

Used as a drug, it has previously been shown to suppress relapses and inhibit clinical attacks in animal models of MS when fed to the animals. When the drug is delivered to the animals by injection, higher doses are required to achieve the same effects.

In this study, the researchers set out to find the doses of IFN that were best at inhibiting relapses in mice with EAE (an animal model of MS) when administered orally or by subcutaneous injection.

They found that the optimum dose of IFN was 10 times lower when it was fed to the mice than when it was injected.

Furthermore, when the responses of the mice to the optimum dose of IFN delivered orally was compared to the optimum dose delivered subcutaneously, the orally-delivered drug was found to be by far the most effective at inhibiting relapses.

Specific responses of immune cells to different types of stimulations were also looked at in the mice, and in many cases oral IFN inhibited the responses whereas injected IFN did not. Sometimes injected IFN actually increased the responses of the immune cells.

Therefore, not only is the oral route a more convenient way to deliver IFN than by subcutaneous injection, it also appears to be more effective, at least in mice.

SA Brod, M Khan
Journal of AutoImmunity 9: 1 (FEB 1996) Page(s) 11-20
SA Brod,
Univ Texas, Hlth Sci Ctr, Dept Neurol 7044, POB 20708, Houston, TX 77225 USA


8) Comparison of two Neurologic Scoring Instruments for Multiple Sclerosis

Summary: The Extended Disability Status Scale (EDSS) and the Scripps Neurologic Rating Scale (SNRS) are two different scales that are used to asses neurologic impairment.

Although different, these two scales supposedly measure more or less the same thing, and so should correlate with each other for any given patient with a particular condition.

This study was performed to examine just how closely these two scales actually do correlate.

The two scales were independently employed to measure patients' neurologic abilities in a clinical trial in which the usefulness of the drug Cladribine in treating Chronic Progressive Multiple Sclerosis was tested.

If both the scales were equally able to assess neurologic impairment, it would be expected that when a patient benefited from the drug, both scales would indicate a similar reduction in impairment.

Surprisingly, the EDSS and the SNRS did NOT give results that strongly correlated when used to assess an individual's response to the drug. In fact, in 9 out of 48 patients, the actual direction of change from baseline were different using the two scales (that is, one scale indicated the patient had improved and the other scale indicated that the patient's impairment had worsened).

There were also differences in the way the two scales measured clinical changes over time, with one scale indicating a fast rate of change and the other indicating a slower, more gradual change.

Although this study does not go as far as to favor one scale over the other as a tool for measuring neurologic impairment, it does suggest that further study should be done in future clinical trials to more thoroughly asses the validity of the EDSS and the SNRS.

JA Koziol, A Frutos, JC Sipe, JS Romine, E Beutler
Journal of Neurology 243: 3 (MAR 1996) Page(s) 209-215
JA Koziol, Scripps Clin & Res Inst, Dept Molec & Exptl Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA


9) Acyclovir Treatment of R/R Multiple Sclerosis: A Randomized, Placebo-Controlled, Double-Blind Study

Summary: It is thought that Viral infections might contribute towards relapses of Multiple Sclerosis episodes. The purpose of this study was to test the idea that infection with a particular virus, the Herpes Virus, might play a role in MS disease.

Sixty patients with the Relapsing/Remitting form of MS were randomly assigned to either a placebo control group or a group which was given oral treatment with the anti-herpes virus drug Acyclovir 3 times a day.

After 2 years the number of relapses that people from each group had experienced was compared.

Although there was a 34% reduction in the number of relapses in the Acyclovir-treated group this was not statistically significant.

However, if the patients were grouped according to relapse frequency (low, medium, or high numbers of relapses), or if the number of relapses for an individual for the 2 years prior to entering this clinical trial were compared with the number of relapses that individual had while in the Acyclovir trial, then a significant reduction in relapse frequency was observed.

Other than relapse frequency, acyclovir did not seem to affect a variety of neurological parameters, and neurological deterioration was NOT slowed down by the drug.

The results of this study suggest that Acyclovir might be able to be used to reduce the relapse frequency in patients with MS, and it also provides support for the idea that infection with Herpes Viruses (or other Acyclovir-sensitive viruses) might be involved in MS disease progression.

J Lycke, B Svennerholm, E Hjelmquist, L Frisen, G Badr, M Andersson, A Vahlne, O Andersen
Journal of Neurology 243: 3 (MAR 1996) Page(s) 214-224
J Lycke, Gothenburg Univ, Sahlgrens Hosp, Dept Neurol, S-41345 Gothenburg, Sweden


10) Functional & NeuroPhysiological Evidence of the Efficacy of Trophic Pharmacotherapy using AdrenoCorticoTrophic Hormone Analog in Experimental Allergic EncephaloMyelitis

Summary: One possible approach to the treatment of MS could be to try to repair Neurological damage as it occurs.

This might be done by using analogues of naturally occurring Hormones or chemicals that support nerve growth and repair.

In this paper, the effectiveness of one such drug (AdrenoCorticoTrophic Hormone analogue) was tested on an animal (rat) model of MS. A variety of neurological parameters were studied.

Repeated subcutaneous injections suppressed the development of disease symptoms in the rats and improved motor function (movement) as well as the time it took the animals to react after being touched by a hot object. Other more specific neurological parameters were also improved by the drug.

Therefore, this study suggests that the Neurological repair approach to MS treatment might indeed be valuable in helping to restore motor function affected people.

Much more study is necessary, however, before this particular treatment can be tried on people.

HJ Duckers, RP Vandokkum, J Verhaagen, FHL Dasilva, WH Gispen
NeuroScience 71: 2 (MAR 1996) Page(s) 507-521
WH Gispen,
Univ Utrecht, Fac Med Rudolf Magnus Inst NeuroSci, Dept Med Pharmacol, 3521 Gd Utrecht, Netherlands



 

11) Cell-Cell Interactions During the Migration of Myelin-Forming Cells Transplanted in the DeMyelinated Spinal Cord

Summary: The authors transplanted Myelin-forming cells into mice that had damaged Nerve cells. The cells were transplanted at a distance from the damaged site to see if the cells would move to the damaged area after transplantation.

The transplanted cells called (Schwann cells) were found at the damaged site showing that these cells can indeed move in adult mice to a site of damage.

The authors go on to describe the exact locations of these cells and the possible route of migration.

They conclude that the movement pattern of these repair cells is determined by a number of differenT-Cell types in the Central Nervous System of the mouse and because there are a number of differenT-Cells involved in the process it must be quite complex.

A Baronvanevercooren, V Avellanaadalid, A Benyouneschennoufi, A Gansmuller, B Naitoumesmar, L Vignais
Glia 16: 2 (FEB 1996) Page(s) 147-164
A Baronvanevercooren, Hop La Pitie Salpetriere, Inserm U134, Lab NeuroBiol Cellulaire, 47 BVD Hop, F-75651 Paris 13, France



12) Pentoxifylline, a Phosphodiesterase Inhibitor, Induces Immune Deviation in Multiple Sclerosis

Summary: Drugs which can modify the Immune System are potential candidates for MS therapy. T-Cells are integral components of the Immune System and are thought to play a role in the development of the disease.

These cells produce compounds called Cytokines which attract and stimulate other Immune cells.

A certain type of T-Cells called T-Helper type 1 (Th1) produce Cytokines that cause inflammation whereas a second set of T-Cells called T helper type 2 (Th2) produce Cytokines which stimulate B-Cells to produce AntiBodies.

Immunotherapy of AutoImmune Diseases such as MS may be achieved by inhibiting the production of Cytokines from Th1 cells and stimulating Cytokine production of Th2.

The scientists examined a compound called Pentoxifylline (PTX) which has been found to inhibit the production of some Th1 Cytokines and stimulates the production of some Th2 cytokines. Eight patients with Relapsing/Remitting MS were treated with PTX and Cytokine levels were measured in their blood.

Two inflammatory Cytokines called Tumor Necrosis Factor alpha and InterLeukin-12 (the Th1 type) were found to be significantly decreased whereas InterLeukin-4 and -10 (the Th2 type) were found to be elevated in the MS patients treated with PTX.

These results indicate that PTX modulates the Immune System in a favorable way and may have potential benefits as a treatment for MS. More studies are needed.

P Rieckmann, F Weber, A Gunther, S Martin, A Bitsch, A Broocks, B Kitze, T Weber, T Borner, S Poser
Journal of NeuroImmunology 64: 2 (FEB 1996) Page(s) 193-200
P Rieckmann,
Univ Wurzburg, Neurol Klin & Poliklin, Josef Schneider Str 11, D-97080 Wurzburg, Germany

 



13) Impact of Aerobic Training on Fitness & Quality of Life in Multiple Sclerosis

Summary: Fifty-four MS patients were grouped into either an exercise group (EX) or nonexercise group (NEX). The EX group underwent 3 X 40 minute sessions per week of leg and arm exercises.

At the beginning of the study and after 15 weeks of aerobic training the participants were measured for various fitness factors including aerobic capacity, isometric strength, body composition, and blood lipids. Various other factors, such as daily activities, mood, fatigue and disease status were monitored in both groups.

The EX group showed a number of improvements over the NEX group such as improved bowel and bladder function, upper and lower extremity strength, and aerobic capacity.

There were also significant decreases in skinfolds, triglyceride, and very-low-density lipoprotein (VLDL).

After five weeks depression and anger levels were lower and after ten weeks there was a reduction in fatigue.

In general, the exercise improved the quality of life and resulted in improved fitness in the MS patients studied.

JH Petajan, E Gappmaier, AT White, MK Spencer, L Mino, RW Hicks

Annals of Neurology 39: 4 (APR 1996) Page(s) 432-441

JH Petajan,
Univ Utah, Dept Neurol, Salt Lake City, UT 84112 USA



 

14) Safety Profile of Copolymer-1 (Copaxone): Cumulative Experience in United States & Israel

Summary: This article summarizes the data accumulated so far regarding the treatment results of Copolymer 1 (Copaxone) on MS. A total of 857 patients to date (mainly with Relapsing/Remitting MS) have been enrolled in various trials.

The typical dose of Copaxone was 20 milligrams by daily injection for at least one year and sometimes for more than 10 years.

The most common side effect of the drug was redness and inflammation at the injection site and the most adverse event, which occurred in 10% of patients, was a whole body reaction including flushing, chest tightness, anxiety, rapid and irregular heart beat and was acute and transient.

The authors suggest that the use of Copaxone appears to be well tolerated and suitable for self-administration by MS patients.

AD Korczyn, P Nisipeanu
Journal of Neurology 243: 4 Suppl. 1 (APR 1996) Page(s) S23-S26
AD Korczyn, Sackler Fac Med, IL-69978 Ramat Aviv, Israel



15) ImmunoGlobulins Reactive with Myelin Basic Protein Promote CNS ReMyelination

Summary: This study tested the idea that AntiBodies directed against Myelin Basic Protein might help Remyelination caused by Immune mediated DeMyelinating diseases like MS.

As an animal model of MS, they used mice infected with Theiler's Virus. These mice develop extensive DeMyelination and inflammation and show relatively low levels of ReMyelination.

When the mice were treated with AntiBodies specifically directed against Myelin Basic Protein, they responded by increasing their production of new Myelin.

Also, essentially no inflammatory cells were found in the ReMyelinated lesions, even though the virus was still present in the Spinal Cord.

These results suggest that AntiBodies against Myelin proteins may potentially promote Myelin repair in individuals with MS.

M Rodriguez, DJ Miller, VA Lennon
Neurology 46: 2 (FEB 1996) Page(s) 538-545
M Rodriguez, Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Immunol, Rochester, MN 55905 USA



16) Side Effect Profile of Interferon-ß-1b in MS: Results of an Open Label Trial

Summary: 72 MS patients who had started Interferon-ß-1b therapy after its release as a treatment for MS were studied. The purpose was to see which type of patient is most susceptible to side effects from this drug and which side effect are the most problematic.

Skin reactions, flu-like symptoms, fatigue, leukopenia (decrease in white blood cells), new or worsened depression, and new or worsened headache were the most significant side effects associated with drug.

The patients who suffered from fatigue and depression were the ones who were most likely to stop using Interferon-ß-1b.

In addition, if the patients taking the drug had a chronic progression of the disease (even though the drug appeared to be beneficial in reducing the attack rate), they were also more likely to discontinue treatment.

The authors suggest that in future clinical trials of Interferon-ß-1b, the side effects of fatigue and depression will have to be lessened in order to reduce the number of patients who stop taking the drug.

LK Neilley, DS Goodin, DE Goodkin, SL Hauser
Neurology 46: 2 (FEB 1996) Page(s) 552-554
DS Goodin,
Univ Calif San Francisco, Dept Neurol, M-794, 505 Parnassus Ave, San Francisco, CA 94143 USA



17) Subcutaneously Insulin-like Growth Factor-I Reduces Clinical Deficits, Decreases Lesion Severity & Upregulates Synthesis of Myelin Proteins in Experimental AutoImmune EncephaloMyelitis

Summary: In this study, the effects of a naturally occurring hormone called Insulin-like Growth Factor-1 (IGF-1) on treating MS was assessed using the animal model Experimental AutoImmune EncephaloMyelitis (EAE).

IGF-1 treatment was started on the animals when they started showing definite clinical weakness.

It was found that IGF-1 given subcutaneously (under the skin) or intravenously (injected into a vein) significantly reduced both clinical symptoms and lesion severity.

IGF-1 treatment also appeared to promote Myelin regeneration, as assessed by an increase in production of Myelin components.

These results suggest that IGF-1 may be useful in treating Multiple Sclerosis patients with active DeMyelination.

DL Yao, X Liu, LD Hudson, HD Webster
Life Sciences 58: 16 (MAR 15 1996) Page(s) 1301-1306
HD Webster, Nincds, NIH, Exptl Neuropathol Lab, Bldg 36, RM 4A29, Bethesda, MD 20892 USA


18) Intramuscular Interferon-ß-1alpha for

Disease Progression in R/R Multiple Sclerosis

Summary: This study reports on the findings of a phase III clinical trial of the drug Interferon-ß-1a (AvonexTM).

It was carried out at a number of different medical centers and was initiated to determine if Interferon beta-1a was effective at slowing the progression of Neurological disability in Relapsing MS patients.

301 patients with Relapsing MS were randomly assigned to treatment or placebo control groups. Weekly injection of the drug (6 million units) or the placebo was given, and the patients were monitored for the time it took them to progress in their disability, as measured on a commonly used disability status scale called EDSS.

It was found that patients treated with Interferon-ß-1a took a significantly longer time to progress one point further down the disability scale than those in the control group.

The drug treated patients also had significantly fewer exacerbations and a significantly lower number and volume of Brain lesions assessed by Magnetic Resonance Imaging.

Therefore, this major study concludes that Interferon-ß-1a (AvonexTM) is significantly beneficial in reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity in patients with Relapsing MS.

Since this drug differs from standard therapies by actually slowing the progression of physical disability in MS patients rather than only treating the symptoms, its use may change the course of this disease.

LD Jacobs, DL Cookfair, RA Rudick, RM Herndon, JR Richert, AM Salazar, JS Fischer, DE Goodkin, CV Granger, JH Simon, JJ Alam, DM Bartoszak, DN Bourdette, J Braiman, CM Brownscheidle, ME Coats, SL Cohan, DS Dougherty, RP Kinkel, MK Mass, FE Munschauer, RL Priore, PM Pullicino, BJ Scherokman, B Weinstockguttman, RH Whitman, WC Baird, M Fillmore, LM Bona, ME Colonruiz, BS Nadine, A Donovan, S Bennett, YM Kieffer, MA Umhauer, CE Miller, AK Kilic, EL Sargent, M Schachter, DW Shucard, V Weider, BA Catalano, JM Cervi, C Czekay, JL Farrell, JS Filippini, RC Matyas, KE Michienzi, M Ito, etal.
Source Annals of Neurology 39: 3 (MAR 1996) Page(s) 285-294
LD Jacobs, Buffalo Gen Hosp, Dept Neurol, 100 High St, Buffalo, NY 14203 USA


19) Comparative Effects of Interferon-Consensus:

Interferon-alpha(2a), and Interferon-ß(1b), on HLA Expression & LymphoProliferation:

A Preclinical Model for Treatment of Multiple Sclerosis

Summary: Interferon-ß-1b is a naturally occurring chemical in the immune system and is being used to treat Multiple Sclerosis. It is a member of a larger family of chemicals called type 1 Interferons.

A synthetic protein has been created which is put together from the most common pieces of the different interferons. This new synthetic protein is called IFN-Con 1 for (Interferon-consensus 1), it has been shown to have greater biological activity in many situations when compared to the natural Interferons.

Since IFN-Con 1 might prove to be more potent that Interferon-ß-1b in some regards, including the treatment of MS, its biological effects must be further studied. The authors of this paper investigated a number of different activities of IFN-Con 1.

They concluded that in many ways it had effects that were similar to other Class 1 Interferons which might make it a possible candidate for use as a treatment for AutoImmune Diseases.

S Dhibjalbut, H Jiang, QA Xia, L Blatt, KP Johnson, D Hilt
Journal of Interferon and Cytokine Research 16: 3 (MAR 1996) Page(s) 195-200
S Dhibjalbut,
Univ Maryland Hosp, Dept Neurol, 22 S



20) Selective Depletion of Myelin-Reactive T-Cells with the Anti-OX-40 AntiBody Ameliorates AutoImmune EncephaloMyelitis

Summary: OX-40 is a protein which is produced in larger quantities on T-Cells that react against Myelin Basic Protein (MBP). These T-Cells are found at the site of inflammation at the onset of Experimental AutoImmune EncephaloMyelitis (EAE).

The scientists in this study used a Toxin, called OX-40 ImmunoToxin, which binds and eliminates MPB-specific T-Cells without affecting other T-Cells. The destruction of these T-Cells resulted in an improvement of mice with this disease.

The unique expression of OX-40 on the surface of these T-Cells may provide a new therapeutic strategy for the elimination of these T-Cells and a potential therapy for MS patients.

AD Weinberg, DN Bourdette, TJ Sullivan, M Lemon, JJ Wallin, R Maziarz, M Davey, F Palida, W Godfrey, E Engleman, RJ Fulton, H Offner, AA Vandenbark
Nature Medicine 2: 2 (FEB 1996) Page(s) 183-189
 AD Weinberg, Providence Med Ctr, Earle a Chiles Res Inst, 4805 NE Glisan, Portland, OR 97213 USA



21) Intravenous Antigen Administration as Therapy for AutoImmune DeMyelinating Disease

Summary: Experimental Allergic EncephaloMyelitis (EAE) is a DeMyelinating Disease induced in rodents, which is similar to MS.

The authors have previously shown that the administration of high doses of Myelin Basic Protein (MBP) relieved some of the clinical signs and damaging effects of EAE through the destruction of MBP-specific T-Cell.

In this study they demonstrate that multiple injections are required to acquire a therapeutic effect. This form of therapy works even after prolonged chronic disease.

The inclusion of a Cytokine (InterLeukin-2) actually aggravated the clinical symptoms compared to the Antigen (MBP) alone.

These experiments support the rationale for this kind of therapy which results in the decrease of specific AutoImmune T-Cells in mice. This type of strategy may be eventually used as a treatment for MS patients.

MK Racke, JM Critchfield, L Quigley, B Cannella, CS Raine, HF Mcfarland, MJ Lenardo
Annals of Neurology 39: 1 (JAN 1996) Page(s) 46-56
MK Racke, Washington Univ, Sch Med, Dept Neurol, Box 8111, 660 S Euclid Ave, St Louis, MO 63110 USA



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