Promoting ReMyelination As A Future Therapeutic Principle In Multiple Sclerosis?
Pohlau D, Aktas O, Epplen C, Hartung HP, Hoffmann V, Przuntek H
Unique AutoAntiBodies Promote Central Nervous System ReMyelination
Asakura K, Rodriguez M
Failure of IntraVenous ImmunoGlobulin To Arrest Progression Of Multiple Sclerosis
A clinical and MRI based study
Due to the modest benefit, inconvenience and high cost of currently available therapies for MS, it is appropriate to seek alternative treatments.
Based on anecdotal evidence suggestive of benefit for IVIG in MS, we conducted an open-label, unblinded protocol of I.V.IG in nine MS patients.
The patients were given induction doses of IVIG followed by monthly boosters for 1 year and had clinical, MRI and CSF analyzes performed. Patients included were both Progressive and Relapsing.
There was no clinical benefit nor apparent MRI benefit utilizing this protocol.
During treatment the majority of patients continued to progress or have attacks and MRI demonstrated continued accumulation of T2-weighted lesions. CSF was unaffected by treatment.
IntraVenous ImmunoGlobulin therapy: Effects Of Acute And Chronic Treatment In Multiple Sclerosis
Trial Of IV ImmunoGlobulin In Multiple Sclerosis
We enrolled 25 patients with Relapsing/Remitting or Relapsing/Progressive Multiple Sclerosis (MS) in a randomized placebo-controlled double-blind study of IntraVenous ImmunoGlobulin (IVIG).
IVIG 1 g/kg daily for 2 days was administered every 4 weeks for 24 weeks.
Seventeen patients completed the whole trial, whereas eight patients discontinued the trial; four during IVIG treatment and four on placebo.
Of the 17 patients who completed the trial, 11 had no exacerbations during IVIG treatment compared with only six on placebo (P=O.05).
The total number of exacerbations in the IVIG period was 11 and in the placebo period 15 (NS), and the number of severe exacerbations requiring treatment with IntraVenous MethylPrednisolone was four during treatment with IVIG and six on placebo (NS).
The results suggest that IVIG treatment may be of benefit for prevention of exacerbations in patients with Relapsing MS.
Treatment Effects Of Monthly IntraVenous ImmunoGlobulin In R/R Multiple Sclerosis
Further Analyzes Of The Austrian ImmunoGlobulin In MS Study
Recently, the Austrian ImmunoGlobulin in Multiple Sclerosis (AIMS) study showed patients with Relapsing/Remitting Multiple Sclerosis to benefit from repeated administration of IntraVenous ImmunoGlobulin (IVIg).
To provide a more detailed understanding of IVIG's action we performed further analyzes on the time course of treatment effects and in regard to the impact of clinical disability at study entry on patients' response to medication.
The AIMS trial was a randomized, placebo-controlled, double blind, multicenter trial.
It included 148 patients (IVIG: 75; placebo 73) who suffered from Relapsing/Remitting MS, were 15-65 years old and scored from 1-6 on the Expanded Disability Status Scale (EDSS).
IVIG was given over 2 years in a monthly dosage of 0.15-0.2 g/kg body weight.
Within the first 6 months of the trial clinical disability of IVIG treated patients improved significantly from a baseline EDSS of 3.33 +/- 1.38 to a score of 3.05 +/- 1.73 (P=0.002).
This improvement was retained over the subsequent 18 months of the trial (final EDSS: 3.09 +/- 1.62).
In contrast, placebo-treated patients showed a slight trend for deterioration over the study period (baseline EDSS: 3.37 +/- 1.67; final EDSS: 3.49 +/- 1.83).
IVIG treatment was associated with a significant reduction of relapses throughout the study which was independent of the patients' disability at baseline.
The observation of clinical improvement in the early phase of IVIG medication may suggest the activation of repair mechanisms.
Such as the promotion of ReMyelination while ImmunoRegulatory effects would be expected as the cause of fewer exacerbations throughout the AIMS study. These hypotheses need to be tested in future trials.
Promotion Of Endogenous ReMyelination In Multiple Sclerosis
Lucchinetti CF, Noseworthy JH, Rodriguez M