Views and opinions of the general public about the reimbursement of expensive medicines in the Netherlands.

Objectives: Solidarity-based healthcare systems are being challenged by the incremental costs of new and expensive medicines for cancer and rare diseases. To regulate reimbursement of such drugs, the Dutch government introduced a policy instrument known as the Coverage Lock (CL) in 2015. Little is known about the public opinion regarding such policy instruments and their consequences, i.

Patient-specific responses to splice-modifying treatments in spinal muscular atrophy fibroblasts.

The availability of three therapies for the neuromuscular disease spinal muscular atrophy (SMA) highlights the need to match patients to the optimal treatment. Two of these treatments (nusinersen and risdiplam) target splicing of , but treatment outcomes vary from patient to patient. An incomplete understanding of the complex interactions among SMA genetics, SMN protein and mRNA levels, and gene-targeting treatments, limits our ability to explain this variability and identify optimal treatment strategies for individual patients.

Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3.

Background And Objective: Proximal spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motor neuron protein. Although primarily a hereditary lower motor neuron disease, it is probably also characterized by abnormalities in other organs. Brain abnormalities and cognitive impairment have been reported in severe SMA.

The Role of Complement Activation in IgM M-Protein-Associated Neuropathies.

Background And Objectives: Polyneuropathy associated with an immunoglobulin M (IgM) monoclonal gammopathy is characterized by slowly progressive, predominantly distal sensorimotor deficits, sensory ataxia, and electrophysiologic features of demyelination. IgM antibodies against myelin-associated glycoprotein (MAG) are present in serum from most patients. Nerve damage most likely results from the concerted action of binding of anti-MAG antibodies to nerves, followed by complement activation.

Complement activation by IgM autoantibodies linked to immune-mediated neuropathies depends on C2.

Background And Purpose: Complement factor C2 is a potential therapeutic target in immune-mediated neuropathies. However, literature suggests that classical complement pathway activation may proceed to C3 in the absence of C2, a so-called "C2 bypass." Here, we evaluated a C2 bypass mechanism during complement activation by pathogenic human IgM from patients with immune-mediated neuropathies.