Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder characterized by hyperkeratotic follicular papules, orange-red scaling plaques with islands of sparing and palmoplantar keratoderma. While spontaneous resolution occurs in some cases, treatment can be challenging for others. The use of biologics in PRP management has gained attention in recent studies, although their high costs and potential side effects present limitations. We present a case of a 71-year-old patient with treatment-resistant PRP who showed significant improvement through optimized adalimumab treatment. Considering the emerging role of phospholipase A2 in PRP pathogenesis, montelukast was added, further enhancing the therapeutic response. By maintaining montelukast and prolonging the adalimumab interval to 3 and 4 weeks, effective dose optimization was achieved without PRP relapse. This case report highlights the potential for adalimumab dose optimization by shortening the initial treatment interval for increased effectiveness and lengthening the interval during the maintenance phase to conserve medication doses. Montelukast appears to assist in sustaining clinical outcomes during interval prolongation, necessitating further investigation through additional studies.
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http://dx.doi.org/10.3389/fmed.2023.1295777 | DOI Listing |
Alzheimers Dement
December 2024
School of Pharmacy, Chapman University, Irvine, CA, USA.
Background: Although novel treatments for Alzheimer's disease (AD) have begun to show modest therapeutic effects, agents that target hallmark AD pathology and offer neuroprotection are desired. Erythropoietin (EPO) is a glycoprotein hormone with neuroprotective effects but is faced with challenges including limited brain uptake and increased hematopoietic side effects with long-term dosing. Therefore, EPO has been modified and bound to a chimeric transferrin receptor monoclonal antibody (cTfRMAb); the latter shuttles EPO past the blood-brain barrier (BBB) into brain parenchyma and reduces its plasma exposure and potential for side effects.
View Article and Find Full Text PDFBackground: Selecting the optimal dose for clinical development is especially problematic for drugs directed at CNS-specific targets. For drugs with a novel mechanism of action, these problems are often greater. We describe Xanamem's clinical pharmacology, including the approach to dose selection and proof-of-concept studies.
View Article and Find Full Text PDFBackground: Progranulin (GRN) plays a critical role in familial frontotemporal dementia (fFTD), where GRN haploinsufficiency leads to reduction in PGRN levels in the brain, resulting in degeneration of neurons in the frontal lobe of brain responsible for personality, language, and behavior. FTD is the most common dementia in people under 60. Sortilin (Sort1), expressed by neurons, endocytoses, and delivers PGRN rapidly to lysosomes for degradation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Burke Neurological Institute, Weill Cornell Medicine, White Plains, NY, USA.
Background: Benfotiamine, a prodrug of thiamine, raises blood levels by 50-100 times to achieve pharmacologic effects. It provides a novel therapeutic direction addressing a well-characterized brain tissue thiamine deficiency and related changes in glucose metabolism in AD. BenfoTeam is a seamless phase 2A-2B "proof of concept" (POC), double-blind, placebo-controlled RCT investigating tolerability, safety, and efficacy of benfotiamine, as a first-in-class small molecule treatment for early AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Inserm, Sorbonne Université, Centre de Recherche Saint-Antoine, Immune System and Neuroinflammation Laboratory, Hôpital Saint-Antoine, Paris, France.
Background: Chronic innate neuroinflammation mediated by microglia and astrocytes in response to Aβ and pathological Tau species is a cardinal feature of AD that contributes to disease pathogenesis. Accumulating evidence now also highlight an instrumental role of T cells and peripheral-central immune crosstalk in the pathophysiology of AD. Both preclinical and clinical reports suggest the potential therapeutic interest of peripheral immunomodulatory approaches aimed at amplifying regulatory T cells (Tregs), e.
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