Article

Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry

Philipps University of Marburg, Marburg, Hesse, Germany
Journal of Neurology Neurosurgery & Psychiatry (Impact Factor: 5.58). 11/2004; 75(10):1472-4. DOI: 10.1136/jnnp.2003.033399
Source: PubMed

ABSTRACT Active or passive immunisation can mitigate plaque pathology in murine models of Alzheimer's disease (AD). Recently, it has been shown that antibodies against beta-amyloid (Abeta) are present in human immunoglobulin preparations (IVIgG), which specifically recognise and inhibit the neurotoxic effects of Abeta. This study reports the results from a pilot study using IVIgG in patients with AD.
Five patients with AD were enrolled and received monthly IVIgG over a 6 month period. Efficacy assessment included total Abeta/Abeta(1-42) measured in the CSF/serum as well as effects on cognition (ADAS-cog; CERAD) at baseline and at 6 months following IVIgG.
Following IVIgG, total Abeta levels in the CSF decreased by 30.1% (17.3-43.5%) compared to baseline (p<0.05). Total Abeta increased in the serum by 233% (p<0.05). No significant change was found in Abeta(1-42) levels in the CSF/serum. Using ADAS-cog, an improvement of 3.7+/-2.9 points was detected. Scores in the MMSE were essentially unchanged (improved in four patients, stable in one patient) following IVIgG compared to baseline.
Although the sample size of this pilot study is too small to draw a clear conclusion, the results of this pilot study provide evidence for a more detailed investigation of IVIgG for the treatment of AD.

0 Followers
 · 
128 Views
  • Source
    • "In addition, results from the studies conducted on Alzheimer's disease (AD) proved promising for the future (Dodel et al., 2004; Relkin et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Stroke is one of the major reasons of death in the United States and related to adult disability. Despite aggressive research, the treatment approaches of stroke still remains a major clinical problem. Intravenous immunoglobulin (IVIg) is a polyspecific Ig G preparation obtained from plasma of several thousand healthy people (donors). IVIg is an important treatment approach and used for several disorders. The aim of this study was to investigate the potentially beneficial effects of IVIg therapy in experimentally induced ischemia in middle cerebral artery occlusion (MCAo) models of rats. A total of 30 adult male Sprague Dawley rats were used. The rats were divided into two equal groups, each consisting of 15 randomly selected rats: control group (n = 15) and IVIg group (n = 15). Intraluminal filament method was used for establishment of cerebral ischemia. Intraluminal filament was withdrawn after 2 h of MCAo and reperfusion started again and passed to therapeutic stages for all the groups. Physiologic saline solution of 0.5 ml/kg was administered to the control group and 400 mg/kg IVIg was given to the IVIg group rats intravenously. In neurological evaluation, the worst score was determined as 3 and the best score as 0. After routine process, the brain tissue was prepared histopathological investigation. The IVIg group showed significantly better recovery with respect to the control group by neurological examination. The observation of specimens obtained from IVIg groups showed that findings correlate with grade 1 and -2 histopathologically. Nevertheless, ischemic amendments were observed to comply with grade 3 in ischemic areas in control group. IVIg therapy can be used in the treatment of ischemic stroke patients.
    Toxicology and Industrial Health 09/2013; DOI:10.1177/0748233713498461 · 1.71 Impact Factor
  • Source
    • "The potential therapeutic efficacy of IVIG has recently been tested in Alzheimer's disease (AD) patients (Dodel et al. 2002; Relkin et al. 2009). Human clinical studies showed stabilization and even a mild improvement in cognitive function in the patients treated with IVIg (Dodel et al. 2004; Relkin et al. 2009). Furthermore, a recent study demonstrated the protective effects of IVIg against Ab toxicity in primary mouse hippocampal neuronal cultures (Magga et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: J. Neurochem. (2012) 122, 321–332. Intravenous immunoglobulin (IVIg) preparations obtained by fractionating blood plasma, are increasingly being used increasingly as an effective therapeutic agent in treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke and Alzheimer’s disease has been proposed, but little is known about the neuroprotective mechanisms of IVIg. In this study, we investigated the effect of IVIg on downstream signaling pathways that are involved in neuronal cell death in experimental models of stroke and Alzheimer’s disease. Treatment of cultured neurons with IVIg reduced simulated ischemia- and amyloid βpeptide (Aβ)-induced caspase 3 cleavage, and phosphorylation of the cell death-associated kinases p38MAPK, c-Jun NH2-terminal kinase and p65, in vitro. Additionally, Aβ-induced accumulation of the lipid peroxidation product 4-hydroxynonenal was attenuated in neurons treated with IVIg. IVIg treatment also up-regulated the anti-apoptotic protein, Bcl2 in cortical neurons under ischemia-like conditions and exposure to Aβ. Treatment of mice with IVIg reduced neuronal cell loss, apoptosis and infarct size, and improved functional outcome in a model of focal ischemic stroke. Together, these results indicate that IVIg acts directly on neurons to protect them against ischemic stroke and Aβ-induced neuronal apoptosis by inhibiting cell death pathways and by elevating levels of the anti-apoptotic protein Bcl2.
    Journal of Neurochemistry 04/2012; 122(2). DOI:10.1111/j.1471-4159.2012.07754.x · 4.24 Impact Factor
  • Source
    • "IVIg is already approved as therapy for immune deficiency, with good safety and tolerability evidence. In two small studies, short-term immunoglobulin administration in patients with AD was well tolerated, promoted a decrease of total Aβ CSF concentrations, and increased plasma total Aβ concentrations [59] [60], with evidence of improvement or stabilization of cognitive functions . Preliminary data from a phase II RCT confirmed the positive effects on cognition [61] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Since 1992, the amyloid cascade hypothesis has played the prominent role in explaining the etiology and pathogenesis of Alzheimer's disease (AD). It proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs), neuronal cell death, and ultimately dementia. While there is substantial evidence supporting the hypothesis, there are also limitations: (1) SP and NFT may develop independently, and (2) SPs and NFTs may be the products rather than the causes of neurodegeneration in AD. In addition, randomized clinical trials that tested drugs or antibodies targeting components of the amyloid pathway have been inconclusive. This paper provides a critical overview of the evidence for and against the amyloid cascade hypothesis in AD and provides suggestions for future directions.
    03/2012; 2012:369808. DOI:10.1155/2012/369808
Show more