Immunoadsorption with regenerating systems in neurological disorders – A single center experience

Hohenstein, Bernd; Passauer, Jens; Ziemssen, Tjalf; Julius, Ulrich

doi:10.1016/j.atherosclerosissup.2015.02.022

Cited by 16 publications

(17 citation statements)

References 15 publications

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“…IA has been clinically applied 59,60 and it is known that antibodies rapidly return to pretreatment levels. 41 In general, 6 to 8 hours after IA a rebound of antibody plasma titers is seen due to redistribution of tissue-bound antibodies and antibodies from the lymphatic/ interstitial compartment.…”

Section: Discussionmentioning

confidence: 99%

Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates

et al. 2019

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Key Points• IA procedure decrease anti-AAV5 NABs to levels compatible with a successful AAV5 vector readministration.• Patients positive for anti-AAV antibodies could benefit from AAVbased gene therapy after IA treatment.Adeno-associated virus (AAV)-based liver gene therapy has been shown to be clinically successful. However, the presence of circulating neutralizing antibodies (NABs) against AAV vector capsids remains a major challenge as it may prevent successful transduction of the target cells. Therefore, there is a need to develop strategies that would enable AAV-mediated gene delivery to patients with preexisting anti-AAV NABs. In the current study, the feasibility of using an immunoadsorption (IA) procedure for repeated, liver-targeted gene delivery in nonhuman primates was explored. The animals were administered IV with recombinant AAV5 (rAAV5) carrying the reporter gene human secreted embryonic alkaline phosphatase (hSEAP). Seven weeks after the first rAAV treatment, all of the animals were readministered with rAAV5 carrying the therapeutic hemophilia B gene human factor IX (hFIX). Half of the animals administered with rAAV5-hSEAP underwent IA prior to the second rAAV5 exposure.The transduction efficacies of rAAV5-hSEAP and rAAV5-hFIX were assessed by measuring the levels of hSEAP and hFIX proteins. Although no hFIX was detected after rAAV5-hFIX readministration without prior IA, all animals submitted to IA showed therapeutic levels of hFIX expression, and a threshold of anti-AAV5 NAB levels compatible with successful readministration was demonstrated. In summary, our data demonstrate that the use of a clinically applicable IA procedure enables successful readministration of an rAAV5-based gene transfer in a clinically relevant animal model. Finally, the analysis of anti-AAV NAB levels in human subjects submitted to IA confirmed the safety and efficacy of the procedure to reduce anti-AAV NABs. Furthermore, clinical translation was assessed using an immunoglobulin G assay as surrogate.

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Section: Discussionmentioning

confidence: 99%

Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates

et al. 2019

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“…regenerated rather than replaced). 7,93 In adults immunoadsorption has equivalent efficacy to TPE for myasthenic crises 94 and relapses of multiple sclerosis and neuromyelitis optica, 95 with equivalent or superior safety profiles. It is hoped that such systems can be more widely used in future.…”

Section: Priorities For Future Researchmentioning

confidence: 99%

Therapeutic plasma exchange in paediatric neurology: a critical review and proposed treatment algorithm

Eyre

Hacohen

Barton

et al. 2018

Develop Med Child Neuro

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“…Apart from the method itself, specific techniques and treatment regimens have to be taken into account when assessing efficacy and safety of PE and IA. Various regenerable (protein A, recombinant proteins) and non-regenerable (tryptophan, phenylalanine) IA adsorbers are routinely used in clinical practice which feature different binding characteristics with regard to immunoglobulin classes, subclasses, and other plasma proteins [3,4]. For example, protein A adsorbers have a stronger binding affinity to IgG compared to IgA and IgM [3].…”

Section: Introductionmentioning

confidence: 99%

“…Life-threatening complications have been reported in 0.12% of patients [14], and a higher risk of adverse events in patients with neurological diseases compared to non-neurological diseases has been described [13]. On the other hand, IA has repeatedly been described as a safe and well-tolerated procedure [3,4,15]. Two studies in myasthenia gravis found that side effects were reduced in IA compared to PE [11,12].…”

Section: Introductionmentioning

confidence: 99%

Safety and Tolerability of Plasma Exchange and Immunoadsorption in Neuroinflammatory Diseases

Dorst

Fillies

Dreyhaupt

et al. 2020

JCM

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Plasma exchange (PE) and immunoadsorption (IA) are frequently used for treatment of various autoimmune-mediated neurological diseases, including multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), and Guillain–Barré syndrome (GBS). Although both methods are generally regarded as well-tolerated treatment options, evidence for safety and tolerability is low for most indications and largely relies on small case series. In this study, we retrospectively analysed adverse events (AEs) and laboratory changes in 284 patients with various neurological indications who received either PE (n = 65, 113 cycles) or IA (n = 219, 435 cycles) between 2013 and 2020 in our Neurology department. One standard treatment cycle for PE as well as IA consisted of five treatments on five consecutive days. During every treatment, the 2.0–2.5-fold individual plasma volume (PV) was treated in IA, while in PE, the 0.7-fold individual PV was replaced by human albumin solution. Overall, both methods showed an excellent safety profile; no deaths of life-threatening adverse events were recorded. Severe AEs (corresponding to grade 3 on the Common Terminology Criteria for Adverse Events grading scale v5.0) including three patients with sepsis, one pneumonia, and one pneumothorax were present in 5/435 IA cycles (1.1%); in the PE group, no severe AEs were recorded. Furthermore, although advantageous tolerability is generally considered the main advantage of IA over PE, we found that overall frequency of AEs (including grades 1 and 2) was higher in IA (67.1% of all cycles) compared to PE (35.4%; p < 0.001). The low incidence of AEs in PE might be caused by the lower PV exchanged during each treatment (0.7-fold) compared to previous studies which predominantly exchanged the 1.0–1.5-fold PV. In order to verify this hypothesis as well as confirming the efficacy of this lower-dosed scheme, prospective studies comparing different treatment regimens are needed.

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Immunoadsorption with regenerating systems in neurological disorders – A single center experience

Cited by 16 publications

References 15 publications

Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates

Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates

Therapeutic plasma exchange in paediatric neurology: a critical review and proposed treatment algorithm

Safety and Tolerability of Plasma Exchange and Immunoadsorption in Neuroinflammatory Diseases

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