There are several neurological diseases with unmet medical needs in which a single dose of IdeS treatment may be beneficial. Guillian-Barré syndrome is the lead clinical indication in neurology.

Guillain-Barré Syndrome (GBS)

The acute immune-mediated polyneuropathies are classified under the eponym Guillain-Barré syndrome after the authors of early de­scriptions of the disease. GBS is an autoimmune disease, resulting from the generation of autoimmune antibodies and inflammatory cells that cross-react with epitopes on peripheral nerves and roots, leading to demyelination, axonal damage or both. Pathogenesis of GBS is not yet fully understood, but the disease is often triggered by a preceding bacterial or viral infection. In particular, one poten­tial trigger of GBS is infection caused by campylobacter. GBS is a heterogeneous disorder, and several variants of the disease have been identified. Variants are often categorized as demyelinating and axonal. Most often, GBS presents as an acute monophasic para­lyzing illness.

The cardinal clinical features of GBS are rapidly progressive, sym­metrical weakness of the extremities accompanied by absent or depressed deep tendon reflexes. The weakness reaches its highest severity in 4 weeks followed by a plateau phase and then recovery. The weakness can vary from mild difficulty with walking to nearly complete paralysis of all extremity, facial, respiratory, and bulbar muscles.

The standard first line treatment of GBS is either IVIg or plasma exchange (PE), although 30 –50 percent do not respond satisfactory to this treatment. There is a high unmet need as 5 percent of patients are dying and many of the surviving patients are left with physical disability and pain. Overall, the disease is associated with dimin­ished life quality and high costs for society in terms of treatment and reduced work capacity. The incidence of GBS is estimated at 1:100,000. An increase in the occurrence of GBS of 20 peercent is seen with every 10-year rise in age after the first decade of life. The addressable patient population with GBS is estimated to be in the range of 4,200 –13,800.

There is evidence of pathogenic role of IgG in axonal variants of GBS, and most researchers and clinicians believe IgG to play a significant role in demyelinating variants as well.

Anti-GBM antibody disease – or Goodpasture’s disease (GP) – is a form of rapidly progressing glomerulonephritis, which is a collective term for severe acute IgG-mediated glomerular injury, often with pulmonary vasculitis. In rapidly progressing glomerulonephritis renal biopsies demonstrate crescentic glomerulonephritis. IdeS treatment has clear potential in anti-GBM antibody disease and may also be beneficial in other forms of rapidly progressing glomerulonephritis, e.g. lupus nephritis in which soluble immune complex deposition is demonstrated, and in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis.

The presentation of anti-GBM antibody disease is similar to that of other forms of rapidly progressive glomerulonephritis: rapid loss of renal function, proteinuria/hematuria, hypertension and often pulmonary hemorrhage. There is an increased risk of morbidity and mortality from renal failure, pulmonary hemorrhage or complications of treatment.

Patients with anti-GBM antibody disease are routinely treated with glucocorticoids, cyclophosphamide and in severe cases with plasma exchange. The mortality has reduced due to improvement in standard of care, and in 2014 the five-year survival rate exceeded 80 %. With treatment, lung disease usually recovers; however, kid­neys are less able to repair themselves often leaving patients with severe renal involvement with permanent renal failure.

Rapid control of the disease is associated with better outcomes. IdeS has the potential to replace plasma exchange as induction therapy, adjunctive to corticosteroids and cyclophosphamide.