Treatment of multiple system atrophy using intravenous immunoglobulin

Abstract

BackgroundMultiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA.MethodsThis was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment.ResultsNine subjects were enrolled, and seven (2 women and 5 men, age range 55–64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment.ConclusionsTreatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.

Atypical Parkinsonism

“…85,86 Neuroprotective or disease-modifying approaches such as with intravenous immunoglobulin and intra-arterial or intravenous injections of autologous mesenchymal stem cells have shown promising results in pilot studies, but need further confirmation. 87,88 Future studies such as a-syn targeting antibodies are currently planned. 89 …”

Treatment of Neurodegenerative Ataxias With Intravenous Immune Globulin

“…Increased numbers of reactive astrocytes and activated microglial cells were also identified in SCA 3 pontine regions. Another openlabel pilot study performed in nine patients with the neurodegenerative disorder MSA successfully used monthly infusions of the IVIG preparation Privigen ® (dose 0.4 g/kg for 6 months) to effect significant improvements in the Unified Multiple System Atrophy Rating Scale (UMSARS)-I (activities of daily living) and UMSARS-II (motor functions) at endpoint relative to baseline [12].…”

Interventional trials in atypical parkinsonism

“…Immunomodulation with intravenous delivery of immunoglobulins improved activities of daily life and motor scores measured by UMSARS-I and eII in a 6-months open-label trial in a small cohort of 9 MSA patients. Nonetheless, safety and tolerability remain to be established in a large RCT [27]. Currently, a phase 1 trial assessing the effect of active immunization with AFFITOPE ® (PD01A or PD03A) over 1 year is running in MSA (NCT02270489).…”