Anakinra in cerebral haemorrhage to target secondary injury resulting from neuroinflammation (ACTION): Study protocol of a phase II randomised clinical trial

Cliteur, MP; van der Kolk, AG; Hannink, G; Hofmeijer, J; Jolink, WMT; Klijn, CJM; Schreuder, FHBM

doi:10.1177/23969873231200686

Cited by 3 publications

(1 citation statement)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result, anakinra may reach clinically meaningful levels in the CNS, supporting its value in treating neuroinflammatory conditions. It is currently being used in another clinical trial to suppress secondary brain injury after spontaneous intracerebral hemorrhage [333]. This accessibility to the CNS would also be advantageous for treating CNS symptoms in MPS.…”

Section: Interleukin-1 Receptor Antagonist: Anakinramentioning

confidence: 99%

Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy

Ago,

Rintz,

Musini

et al. 2024

IJMS

View full text Add to dashboard Cite

Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) disruption of substrate degradation with pathogenic changes in lysosomal function, (2) cellular dysfunction, secondary/tertiary accumulation (toxins such as GM2 or GM3 ganglioside, etc.), and inflammatory process, and (3) progressive tissue/organ damage and cell death (e.g., skeletal dysplasia, CNS impairment, etc.). For current and future treatment, several potential treatments for MPS that can penetrate the blood–brain barrier and bone have been proposed and/or are in clinical trials, including targeting peptides and molecular Trojan horses such as monoclonal antibodies attached to enzymes via receptor-mediated transport. Gene therapy trials with AAV, ex vivo LV, and Sleeping Beauty transposon system for MPS are proposed and/or underway as innovative therapeutic options. In addition, possible immunomodulatory reagents that can suppress MPS symptoms have been summarized in this review.

show abstract

Section: Interleukin-1 Receptor Antagonist: Anakinramentioning

confidence: 99%

Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy

Ago,

Rintz,

Musini

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

Intracerebral haemorrhage — mechanisms, diagnosis and prospects for treatment and prevention

Seiffge,

Fandler-Höfler,

et al. 2024

Nat Rev Neurol

View full text Add to dashboard Cite

New targets in spontaneous intracerebral hemorrhage

Chiang,

Tsai,

Tsai

2024

Current Opinion in Neurology

View full text Add to dashboard Cite

Purpose of review Intracerebral hemorrhage (ICH) is a devastating stroke with limited medical treatments; thus, timely exploration of emerging therapeutic targets is essential. This review focuses on the latest strategies to mitigate secondary brain injury post-ICH other than targeting surgery or hemostasis, addressing a significant gap in clinical practice and highlighting potential improvements in patient outcomes. Recent findings Promising therapeutic targets to reduce secondary brain injury following ICH have recently been identified, including attenuation of iron toxicity and inhibition of ferroptosis, enhancement of endogenous resorption of hematoma, and modulation of perihematomal inflammatory responses and edema. Additionally, novel insights suggest the lymphatic system of the brain may potentially play a role in hematoma clearance and edema management. Various experimental and early-phase clinical trials have demonstrated these approaches may potentially offer clinical benefits, though most research remains in the preliminary stages. Summary Continued research is essential to identify multifaceted treatment strategies for ICH. Clinical translation of these emerging targets could significantly enhance the efficacy of therapeutic interventions and potentially reduce secondary brain damage and improve neurological recovery. Future efforts should focus on large-scale clinical trials to validate these approaches, to pave the way for more effective treatment protocols for spontaneous ICH.

show abstract

Anakinra in cerebral haemorrhage to target secondary injury resulting from neuroinflammation (ACTION): Study protocol of a phase II randomised clinical trial

Cited by 3 publications

References 30 publications

Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy

Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy

Intracerebral haemorrhage — mechanisms, diagnosis and prospects for treatment and prevention

New targets in spontaneous intracerebral hemorrhage

Contact Info

Product

Resources

About