Gene therapy

…discussions address cardiovascular gene therapy, precision medicine, trial design and causal inference, cardiometabolic disease, and the ro

…mouse and cellular models, AAV gene therapy, CRISPR or siRNA perturbations, microscopy, biochemical assays and electrophysiology, with connections to clinical research. This full-time postdoctoral position remains open until filled. The advertised starting salary is USD 63,480, with compensation commensurate with experience.

…stem cell transplantation (HSCT) or gene therapy (GT) when applied at early disease stages. Currently, eligibility for treatment is determined by MRI-based brain lesion Loes scoring. However, this grading system poorly reflects later disease stages or atypical lesion patterns. As such, there is a need for alternative biomarkers to help with treatment decisions. We recently identified inflammatory activity and CALD progression being ref

Technological advances have made Gene therapy a promising therapeutic strategy for a wide range of neurodegenerative diseases. Adeno-associated viruses (AAVs) have demonstrated significant potential as safe and effective vectors for the delivery of therapeutic genes to the CNS. Despite the tremendous promises of AAV-based gene therapies, the pathway to develop these therapies from bench to clinic remains complex and arduous. In response to these challenges, we introduce the BrainVector project, a comprehensive cross-disciplinary platform that streamlines the pre-clinical development of AAV-bas

…by loss-of-function of the SLC6A8 gene. CTD clinical manifestation follows brain creatine (Cr) deficiency and predominantly leads to neurological symptoms such as intellectual disability, language disturbance, psycho-motor impairment, autistic-like behavior, and seizures. We used a murine model to probe whether perinatal adeno-associated virus (AAV)-mediated expression of a functional SLC6A8 transgene under the control of a ubiquitous promoter could restore creatine transporter (CRT) expression and brain Cr level, thus pr

The clinical challenge posed by spinal cord injury (SCI) remains a significant and unresolved issue. Engineering a treatment for SCI will require biological repair interventions that restore connectivity through or around lesions. Using a combination of advanced neuroanatomical viral tract tracing, projection-specific and comparative single-nucleus RNA sequencing, bioinformatic techniques, we recently identified a molecularly defined subpopulation of excitatory projection neuron in the mid-thoracic spinal cord that extend axons to the lumbar spinal cord where walking execution centers reside.

Neurodegenerative disorders (NDs) are characterized by a progressive loss of neurons leading to broad symptoms affecting cognition and motor function. Despite extensive research efforts, treatment options remain palliative, and due to increasing incidence of NDs worldwide, novel therapies are necessary. Gene therapy represents an attractive approach for tackling the complex pathology of NDs. CRISPR-mediated gene activation (CRISPRa) encompasses a growing field of biotechnological approaches with exciting implications for gene therapy through upregulation of genetic targets of interest. However

The optical cochlear implant (oCI) utilizes optogenetic stimulation of the spiral ganglion neurons (SGNs) in the cochlea to improve hearing restoration. Preclinical data has shown that this may improve bionic hearing in CI users by targeting smaller areas of the cochlea compared to electrical stimulation.This study investigates the influence of the light emitter characteristics (one/two laser-coupled glass fibers) on the spread of excitation, through a combination of computer simulations and in-vivo multiunit recordings of inferior colliculus activity in Mongolian gerbils that postnatally rece

…Using optogenetics, SGNs are rendered light sensitive following a viral delivery of a Channelrhodopsin (ChR) transgene to the cochlea. Our group has provided in vivo evidence to support the clinical potential of the optical CI, but for clinical translation, it is critical to optimize individual components of the gene therapy. To this end, we have employed

…Therefore, we are developing a gene therapy strategy for focal drug-resistant epilepsy based on the overexpression of specific GABAAR subunits in hippocampal excitatory neurons, aiming at increasing network inhibition and enhancing the effe

Adeno-associated virus (AAV) vectors are the principal vehicle for gene therapy. In a large share of humans, immunity against AAVs can reduce or completely inhibit transgene expression, and can lead to adverse outcomes. The level of immunity can be estimated by assaying AAV neutralization level of the blood serum. Surprisingly, there is no widely adopted sensitive assay for the quantification of AAV neutralization.Results: We developed an in vitro neutralization assay, and quantified its reproducibility and sensitivity via longitudinal evaluation of neutralization in preclinical models and hum

…Understanding AD pathogenesis and identifying targets to prevent, halt, or cure it is a top priority for the global research and medical communities. Aiming to improve AD pathophysiol

…eye diseases caused by photoreceptor degeneration. The absence of the cells that for this primary signal leads to blindness. My interest in RP involves the

…CNS inflammation, and support degenerating axons in people with progressive MS. Understanding why regeneration fails in the progressive MS brain and developing new regenerative approaches is a key priority for the Pluchino Lab. In particular, we aim to elucidate how the immune system, i

…mutations in the SCN1A gene, which encodes for the alpha-subunit of the voltage-gated sodium channel (Nav1.1) and is responsible mainly of GABAergic interneuron excitability. While different therapies based on the upregulation of the healthy allele of the gene are being developed, the dynamics of reversibility of the pathology are still unclear. In fact, whether and to which extent the

One of the major challenges in developing therapeutics for the neurodegenerative disorders is the blood-brain barrier, limiting the availability of systemically administered therapies such as recombinant proteins or monoclonal antibodies from reaching the brain. Direct central nervous system (CNS) gene therapy using adeno-associated virus vectors expressing a therapeutic protein, monoclonal antibody or inhibiting RNA-coding sequences has two characteristics ideal for therapy of neurodegenerative disorders: circumventing the blood-brain barrier by directly expressing the therapy in the brain an

Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP) are vision disorders caused by loss of rod and cone photoreceptors, but downstream retinal neurons also show physiological and morphological changes, resulting in the emergence of hyperactivity and rhythmic firing in many retinal ganglion cells (RGC). We recently discovered that retinoic acid (RA) is a key signal that triggers hyperactivity and that blockers of RA unmask light responses in RGCs that would otherwise be obscured. Recent work is revealing where in the retina circuit RA initiates functional changes. Moreover, int