Jill Buck
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View article: Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease
Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease Open
Background PSEN1, PSEN2, and APP mutations cause Alzheimer’s disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutatio…
View article: Generation of a gene-corrected human isogenic iPSC line from an Alzheimer’s disease iPSC line carrying the PSEN1 H163R mutation
Generation of a gene-corrected human isogenic iPSC line from an Alzheimer’s disease iPSC line carrying the PSEN1 H163R mutation Open
We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer's disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, e…
View article: Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer’s disease
Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer’s disease Open
Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and CSF and is predictive of cognitive function in individuals with Alzheimer’s disease. There has been limited prior work linking neurofilament light…
View article: Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid
Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid Open
Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near the central nervous system (CNS) parenchyma2, and their role in CNS physiology has not been sufficiently w…
View article: Association of<i>BDNF</i>Val66Met With Tau Hyperphosphorylation and Cognition in Dominantly Inherited Alzheimer Disease
Association of<i>BDNF</i>Val66Met With Tau Hyperphosphorylation and Cognition in Dominantly Inherited Alzheimer Disease Open
In DIAD, clinical disease stage and BDNF Met66 were associated with cognitive impairment and levels of site-specific tau phosphorylation. This suggests that pharmacological strategies designed to increase neurotrophic support in the presym…
View article: Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial
Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial Open
Background Veledimex (VDX)-regulatable interleukin-12 (IL-12) gene therapy in recurrent glioblastoma (rGBM) was reported to show tumor infiltration of CD8+ T cells, encouraging survival, but also up-regulation of immune checkpoint signalin…
View article: CTIM-20. FINAL RESULTS OF CONTROLLED IL-12 MONOTHERAPY AND IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA
CTIM-20. FINAL RESULTS OF CONTROLLED IL-12 MONOTHERAPY AND IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA Open
Ad-RTS-hIL-12(Ad) is a gene therapy candidate conditionally expressing IL-12 under the transcriptional control of veledimex(V) acting via the RheoSwitch Therapeutic System® gene switch. Veledimex plasma and tumor PK demonstrated a dose-res…
View article: CTIM-05. COMBINATION OF CONTROLLED INTERLEUKIN-12 GENE THERAPY WITH IMMUNE CHECKPOINT BLOCKADE IN RECURRENT GLIOBLASTOMA: UPDATED RESULTS OF A MULTI-INSTITUTIONAL, OPEN LABEL PHASE 1 TRIAL
CTIM-05. COMBINATION OF CONTROLLED INTERLEUKIN-12 GENE THERAPY WITH IMMUNE CHECKPOINT BLOCKADE IN RECURRENT GLIOBLASTOMA: UPDATED RESULTS OF A MULTI-INSTITUTIONAL, OPEN LABEL PHASE 1 TRIAL Open
A published clinical trial of veledimex (V)-regulatable interleukin-12 (IL-12) gene therapy (“Controlled IL-12”) under the control of a transcriptional switch (RheoSwitch Therapeutic Systemâ, RTSâ) as monotherapy in recurrent glioblastoma …
View article: CTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM)
CTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM) Open
Ad-RTS-hIL-12 (Ad) is a gene therapy candidate for intratumoral (IT) delivery that conditionally expresses IL-12 (IL-12) under the transcriptional control of orally administered veledimex (V) acting via the RheoSwitch Therapeutic Systemâ g…
View article: CTIM-27. PHASE I/II STUDY OF CONTROLLED IL-12 AS IMMUNOTHERAPY FOR DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
CTIM-27. PHASE I/II STUDY OF CONTROLLED IL-12 AS IMMUNOTHERAPY FOR DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) Open
DIPG, which is the leading cause of pediatric brain cancer death with no effective treatment, has neither a highly immunosuppressive nor inflammatory tumor microenvironment (TME). Therefore, eliciting a pro-inflammatory TME may provide the…
View article: Single-subject grey matter network trajectories over the disease course of autosomal dominant Alzheimer’s disease
Single-subject grey matter network trajectories over the disease course of autosomal dominant Alzheimer’s disease Open
Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted in sporadic Alzheimer’s disease, and network properties show associations with the l…
View article: ATIM-25. PD-1 INHIBITION CAN BE COMBINED WITH IL-12 IN SUBJECTS WITH RECURRENT GLIOBLASTOMA
ATIM-25. PD-1 INHIBITION CAN BE COMBINED WITH IL-12 IN SUBJECTS WITH RECURRENT GLIOBLASTOMA Open
Monotherapy with intratumoral Ad-RTS-hIL-12 (Ad), a novel gene therapeutic conditionally expressing IL-12 under the transcriptional control of oral veledimex (V, 20 mg) acting via the proprietary RheoSwitch Therapeutic System® (RTS®), was …
View article: ATIM-18. SURVIVAL OF SUBJECTS WITH RECURRENT GLIOBLASTOMA RECEIVING INTRA-TUMORAL ADMINISTRATION OF IL-12 MANAGED WITH LOW-DOSE DEXAMETHASONE
ATIM-18. SURVIVAL OF SUBJECTS WITH RECURRENT GLIOBLASTOMA RECEIVING INTRA-TUMORAL ADMINISTRATION OF IL-12 MANAGED WITH LOW-DOSE DEXAMETHASONE Open
Ad-RTS-hIL-12 (Ad) is a novel gene therapy, conditionally expressing IL-12 via the RheoSwitch Therapeutic System® (RTS®) gene switch under control of an oral activator ligand, veledimex (V). We previously reported results from 51 subjects …
View article: Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial
Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial Open
An oral small molecule turns on the transcription of human interleukin-12, with biological effects in patients with recurrent high-grade gliomas.
View article: Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease
Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease Open
Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoas…
View article: ATIM-15. A PHASE 1 STUDY OF Ad-RTS-hIL-12 + VELEDIMEX IN ADULTS WITH RECURRENT GLIOBLASTOMA: DOSE DETERMINATION WITH UPDATED OVERALL SURVIVAL
ATIM-15. A PHASE 1 STUDY OF Ad-RTS-hIL-12 + VELEDIMEX IN ADULTS WITH RECURRENT GLIOBLASTOMA: DOSE DETERMINATION WITH UPDATED OVERALL SURVIVAL Open
Ad-RTS-hIL-12 (Ad) is a novel gene therapy expressing IL-12 via the RheoSwitch Therapeutic System® gene switch under control of an oral activator ligand, veledimex (V). We previously reported on an open label Phase I trial describing biolo…
View article: ATIM-26. A PHASE 1 STUDY OF Ad-RTS-hIL-12 + VELEDIMEX IN ADULT RECURRENT GLIOBLASTOMA
ATIM-26. A PHASE 1 STUDY OF Ad-RTS-hIL-12 + VELEDIMEX IN ADULT RECURRENT GLIOBLASTOMA Open
Glioblastoma (GBM) is an aggressive brain tumor affecting ~74,000 people worldwide annually. Recurrent GBM patients have a median overall survival (mOS) of 6–7 months. OS in patients who have failed temozolomide, bevacizumab or equivalent …
View article: PDCT-03. PHASE 1 STUDY OF Ad-RTS-hIL-12 + VELEDIMEX IN PEDIATRIC BRAIN TUMORS
PDCT-03. PHASE 1 STUDY OF Ad-RTS-hIL-12 + VELEDIMEX IN PEDIATRIC BRAIN TUMORS Open
Pediatric glioblastoma has an aggressive clinical course accounting for significant morbidity and mortality among children with brain tumors. Only 10% of children with DIPG survive for 2 years following diagnosis, and less than 1% survive …