Contraindications
Vaccination with live-attenuated or live vaccines is not recommended during treatment and should be administered at least four weeks before starting satralizumab. Side effects
The most common side effects observed were the common cold (nasopharyngitis), headache, upper respiratory tract infection, inflammation of the lining of the stomach, rash, joint pain, extremity pain, fatigue and nausea.The FDA label for satralizumab includes a warning for increased risk of infection, including serious and potentially fatal infections – such as potential reactivation of hepatitis B and tuberculosis. Other warnings and precautions for satralizumab include elevated liver enzymes, decreased neutrophil counts and hypersensitivity reactions. Pharmacology
Mechanism of action
Satralizumab is a humanized IgG2 monoclonal antibody that binds to soluble and membrane-bound human interleukin-6 (IL-6) receptors and thereby prevents IL-6-mediated signal transmission through these receptors.IL-6 is a pleiotropic cytokine that is produced by a large number of cell types and is involved in a variety of inflammatory processes. Patients with NMO and NMOSD have elevated levels of IL-6 in cerebro-spinal fluid and serum during periods of active disease. Some of the pro-inflammatory processes involved in NMOSD are thought to involve IL-6, including the formation of pathological autoantibodies against aquaporin-4 (AQP4), and the permeability of the blood-brain barrier to mediators of inflammation. Efficacy
The effectiveness and safety of satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD) were demonstrated in two 96-week clinical studies.A study of satralizumab as monotherapy for NMOSD included 95 adult participants, 64 of whom had antibodies against AQP4 (i.e. were anti-AQP4 positive).
The amyloid plaque load and dense-core Congo red positive plaque load in the cortex were reduced by both drugs at all doses. The chronic inflammation response (microglial activation) was also reduced by all treatments
Cai HY et al. demonstrated in a study that lixisenatide could reduce amyloid plaques, neurofibrillary tangles and neuroinflammation in the hippocampi of 12-month-old APP/PS1/tau female mice; activation of PKA-CREB signaling pathway and inhibition of p38-MAPK might be the important mechanisms in the neuroprotective function of lixisenatide. So, lixisenatide might have the potential to be developed as a novel therapy for AD
Liu Wet al found an interesting results when comparing exendin-4 (10 nmol/kg), liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen, while both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro-apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The previous results demonstrate that both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of Parkinson disease
Another study done by Kerry Hunter et al. profiled the GLP-1 receptor agonists liraglutide and lixisenatide. The kinetics of crossing the blood brain barrier (BBB), activation of the GLP-1R by measuring cAMP levels, and physiological effects in the brain on neuronal stem cell proliferation and neurogenesis were evaluated. Both drugs were able to cross the BBB.