Animal studies assessing the effect of anti-GAD and antiamphiphysin antibodies
| Effects in experimental animals (reference) | Study design and comments |
|---|---|
| Stiffness and spasms induced in rats resembling human SPS19 | Intraperitoneal injection of high titre of purified IgG antibodies against amphiphysin from a patient with breast cancer and SPS plus encephalitogenic T-helper lymphocytes to disrupt the BBB in rats Comment: Rats treated with control IgG showed no muscle spasms |
| Continuous motor activity in rats with repetitive muscle discharges41 | Intracerebellar and paraspinal administration of IgG to rats from patients with SPS and cerebellar ataxia associated with anti-GAD antibodies. Comment: Abnormal exteroceptive reflexes increased excitability of anterior horn neurons compared to controls |
| Anxious behaviour in rats, resembling agoraphobia43 44 | Passive transfer of IgG to rats from a patient with SPS with prominent anxiety, agoraphobia and GABAA receptor binding in the amygdala assessed with (11)C-flumazenil PET,43 and intrathecal transfer of purified IgG to rats from a patient with SPS and high titre of antiamphiphysin antibodies.44 Comment: Strong immunoreactivity in rats’ neurons of the hippocampus-amygdala region |
| Stiffness of trunk and limb muscles Increased outward rotation of the hind paws and decreased in forced walking time42 | Intrathecal application of purified IgG antiamphiphysin antibodies to rats from two patients with paraneoplastic SPS associated with breast cancer. Comment: Antiamphiphysin antibodies were internalised into neurons by an epitope-specific mechanism and colocalised in vivo with presynaptic vesicular proteins |
| Increased excitability of the spinal cord in mice Increase in glutamate levels in cerebellar nuclei of mice45 | Antibodies from patients with SPS increased glutamate levels and inhibit GAD activity in rats, whereas antibodies from a patient with cerebellar ataxia caused reduction in glycerol turnover and cerebellocortical inhibition but no effect in glutamate levels when administered directly into the cerebellum of rats, suggesting different in vivo effects of anti-GAD antibodies depending on directed epitopes |
| Trend toward reduced activity of mice in day 6, compared to controls38 | Intraperitoneal injections into mice of purified IgG from two patients (one PERM and one SPS) and healthy human controls plus a lipopolysaccharide to increase CNS access of antibodies |
| Impaired procedural spatial functions in rats46 | Intracerebellar injections of anti-GAD antibodies against two epitopes (b96.11 and b78) and saline solution in rats |
| Stiffness-like behaviour with impaired walking and reduced grip strength47 | Intrathecal or intraventricular injections of purified IgG anti-GAD antibodies in rats from a SPS patient and control. Comment: Only intraventricular injections caused manifestations |
BBB, blood brain barrier; CNS, central nervous system; GABAA, γ-aminobutyric acid A; GAD, glutamic acid decarboxylase; PERM, progressive encephalopathy with rigidity and myoclonus; PET, positron emission tomography; SPS, stiff-person syndrome.