Duchenne muscular dystrophy (DMD) is a devastating, life-limiting neuromuscular disorder that has a global prevelance of 21.4 cases per 100,000 live male births. DMD is caused by mutations in the dystrophin gene, which is integral to muscle membrane stability. Mutations in the dystrophin gene lead to inflammation and muscle fibrosis. Current standard-of-care treatments include the use of chronic (or classic) corticosteroids, which can cause significant side effects. Vamorolone is a first-in-class dissociative steroid that acts as a partial agonist to glucocorticoid receptors but as an antagonist to mineralocorticoid receptors, leading to a more favourable side effect profile. Clinical data has shown that vamorolone has similar anti-inflammatory benefits to classic corticosteroids but an improved side effect profile.
Background: Natalizumab is a widely used anti-α4 integrin inhibitor for treating highly active multiple sclerosis. Although clinical and radiological relapses were observed in the pivotal natalizumab trials, severe disease activity after initiation of the drug is a rare phenomenon and has been reported only in isolated cases. Objective: To present a case of a patient who experienced a paradoxical increase in disease activity after the second dose of natalizumab. Methods: We describe the case, review the literature concerning similar cases and suggest possible mechanisms for this phenomenon. Results: Our case involves a patient who developed extensive tumefactive demyelinating lesions and multiple gadolinium-enhancing lesions detected on magnetic resonance imaging after receiving the second dose of natalizumab. A brain biopsy confirmed the presence of demyelination, and the patient’s condition improved after treatment with intravenous methylprednisolone, intravenous immunoglobulin and plasma exchange. Tests for anti-natalizumab antibodies were negative. Conclusions: Paradoxical worsening can occur in the setting of natalizumab treatment, which warrants careful attention and should prompt anti-natalizumab antibody testing. We discuss potential mechanisms. Further research is needed to better understand the mechanisms and risk factors for paradoxical worsening and to develop strategies for mitigating this adverse effect with significant patient impact.
Proton pump inhibitors (PPIs) are commonly used for gastroesophageal reflux disease. Previous studies have raised concerns about the impact of PPIs on cognition in older adults, but the evidence supporting this concern is lacking. This article aims to analyse the available data regarding the impact of long-term PPI use on cognition in older adults. We searched PubMed for relevant studies conducted between 2015 and 2022. Seventeen such studies were identified. Limitations to available research data include the fact that studies are mainly observational, use heterogeneous study methods and do not account for confounding variables such as B12 deficiency, Helicobacter pylori infection, and thyroid dysfunction. Overall, this search did not find a compelling association between PPI use and cognitive decline.
On 6 January 2023, the amyloid beta-targeting antibody lecanemab was approved by the US Food and Drug Administration for the treatment of mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia via its Accelerated Approval pathway. However, two important questions need to be highlighted: What is the appropriate patient population to receive treatment? How much should healthcare systems be prepared to pay for the drug? The healthcare infrastructure is not prepared for the expected huge demands for diagnostics and eventual treatment, especially given the suggested list price and a potentially large population of people with mild cognitive impairment due to AD and mild AD dementia. A lower price point would allow wider access to the treatment and reduce disparities in health equity.
