053 Brainshuttle AD: Investigating safety, tolerability, and PK/PD of RG6102 in prodromal/mild-to-moderate AD

Kulic, Luka; Vogt, Annamarie; Alcaraz, Fabien; Barrington, Philip; Marchesi, Maddalena; Klein, Gregory; Croney, Ruth; Agnew, David J.; Abrantes, João A; Svoboda, Hanno

doi:10.1136/jnnp-2022-abn2.97

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the futility of the GRADUATE I and II trials, the manufacturer has reformulated gantenerumab in combination with their brain shuttle technology to increase transport across the blood-brain barrier. 54 This reformulated agent, RG6102, is currently in phase I and II trials.…”

Section: Discussionmentioning

confidence: 99%

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease

Yoon,

Groff,

Criss

2024

Innov Pharm

View full text Add to dashboard Cite

The Food and Drug Administration granted traditional approval of lecanemab for the treatment of Alzheimer’s disease (AD). Lecanemab is a humanized anti-amyloid monoclonal antibody directed towards Aβ protofibrils. Lecanemab is the only drug that targets Aβ soluble protofils and has shown statistical differences in mild AD or mild cognitive impairment. In its landmark phase III trial, lecanemab was shown to slow the progression of clinical decline, and a reduction in amyloid protein accumulation. The difference in mean CDR-SOB score improvement between the treatment and placebo groups was -0.45, of which the clinical significance could be argued. Amyloid burden was also considerably reduced as well, but the true clinical consequence of this reduction remains to be seen. This beneficial impact on daily living is offset by rare but serious side effects including amyloid-related imaging abnormalities (ARIA) causing cerebral edema (ARIA-E) or cerebral microhemorrhages or hemosiderin deposits (ARIA-H). Benefits of therapy must be considered against the risk of cerebral microhemorrhages and edema. Affordability must also be taken into consideration. The current estimated yearly cost for twice monthly lecanemab infusion is $26,500. In addition to the significant cost challenges, the frequent infusions may pose concerns related to access. Additional agents within this class are in the pipelines with possibly increased efficacy or decreased adverse events.

show abstract

Section: Discussionmentioning

confidence: 99%

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease

Yoon,

Groff,

Criss

2024

Innov Pharm

View full text Add to dashboard Cite

show abstract

“…These promising findings have sparked hope for the development of effective treatments for CNS diseases, particularly mucopolysaccharidosis type II [76][77][78] and AD [79]. With the ongoing clinical trials for RG6102 as a novel antibody therapeutic for AD, the ability of the RMT brain shuttle technology to facilitate the crossing of the blood-brain barrier and target amyloid plaques in AD mouse models has been demonstrated [71,80].…”

Section: Receptor-mediated Transcytosis (Trojan Horse Method)mentioning

confidence: 99%

Enhancing Antibody Exposure in the Central Nervous System: Mechanisms of Uptake, Clearance, and Strategies for Improved Brain Delivery

Schwinghamer,

Siahaan

2023

JNT

View full text Add to dashboard Cite

Antibodies (mAbs) are attractive molecules for their application as a diagnostic and therapeutic agent for diseases of the central nervous system (CNS). mAbs can be generated to have high affinity and specificity to target molecules in the CNS. Unfortunately, only a very small number of mAbs have been specifically developed and approved for neurological indications. This is primarily attributed to their low exposure within the CNS, hindering their ability to reach and effectively engage their potential targets in the brain. This review discusses aspects of various barriers such as the blood–brain barrier (BBB) and blood–cerebrospinal fluid (CSF) barrier (BCSFB) that regulate the entry and clearance of mAbs into and from the brain. The roles of the glymphatic system on brain exposure and clearance are being described. We also discuss the proposed mechanisms of the uptake of mAbs into the brain and for clearance. Finally, several methods of enhancing the exposure of mAbs in the CNS were discussed, including receptor-mediated transcytosis, osmotic BBB opening, focused ultrasound (FUS), BBB-modulating peptides, and enhancement of mAb brain retention.

show abstract

053 Brainshuttle AD: Investigating safety, tolerability, and PK/PD of RG6102 in prodromal/mild-to-moderate AD

Cited by 2 publications

References 0 publications

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease

Enhancing Antibody Exposure in the Central Nervous System: Mechanisms of Uptake, Clearance, and Strategies for Improved Brain Delivery

Contact Info

Product

Resources

About