The TransEuro open-label trial of human fetal ventral mesencephalic transplantation in patients with moderate Parkinson’s disease
This paper reports the predesigned 3-year outcome of the TransEuro trial. A trial transplanting fetal ventral mesencephalic tissue in patients with moderate Parkinson's Disease.
Imaging of human stem cell-derived dopamine grafts correlates with behavioural recovery and reveals microstructural brain changes
This paper uses state-of-the-art PET and MR imaging to investigate whether [18F]Fluorodopa or [18F]Fallypride imaging correlates robustly with functional recovery, and to explore whether diffusion-weighted MR imaging (DWI) could detect graft-induced cytoarchitectural changes in the host brain.
Epigenetic memory of Lateral Ganglionic Eminence derived hiPSCs cannot overcome barriers in authentic MSN differentiation
This paper investigates whether human iPSCs (hiPSC) derived from the lateral ganglionic eminence (LGE) retain sufficient epigenetic features of their original tissue to enhance their capacity to differentiate into striatal medium spiny neurons (MSN) compared to isogenic controls.
Protocol for a randomised controlled unblinded feasibility trial of HD-DRUM: a rhythmic movement training application for cognitive and motor symptoms in people with Huntington’s disease
This paper describes a feasibility trial for a tablet-based drumming application (HD-DRUM) for people with Huntington's disease. The trial aimed to assess the feasibility of a larger future trial, and explore the effects of the intervention on cognitive, motor, and brain function.
Advancing Parkinson’s disease treatment: cell replacement therapy with neurons derived from pluripotent stem cells
This paper provides an overview of the progress in using human pluripotent stem cells (hPSCs) to generate dopaminergic neuron precursors for cell replacement therapy in Parkinson's disease (PD).
Language-Independent Acoustic Biomarkers for Quantifying Speech Impairment in Huntington's Disease
This study demonstrates the potential of using acoustic features derived from mobile device recordings to automatically characterize speech impairment in Huntington's disease (HD) across different languages. The study identified a set of language-independent acoustic and temporal features that differed significantly between HD participants and controls.
This study investigated the role of 7α,26-diHC in midbrain dopamine (mDA) neuron development and survival. We report that 7α,26-diHC induces apoptosis and reduces the number of mDA neurons in hESC-derived cultures and in mouse progenitor cultures.
This paper aimed to understand the organization and resourcing of specialist HD services for people with HD (PwHD) in the UK. This research highlights the variation in organization and capacity within individual HD services as well as current resourcing and gaps in access that influence this capacity.
The aim of this research was to assess the functional consequence of long-term L-DOPA exposure on cognitive and motor function using a rodent model of PD.
This paper investigated the impact of selective genetic potentiation of neuronal ERK signalling on cell death in vitro and in vivo in the mouse brain.
This study aimed to carry out single-cell RNA sequencing (scRNA-seq) of both human and mouse MGE tissue. Revealing species-conserved transcriptomic profiles and regulatory programs. Moreover, we identified novel candidate transcription regulators for human interneuron differentiation.
We evaluated the efficacy of iPSC-DA neuron precursors from two individuals with sporadic PD by transplantation into a hemiparkinsonian rat model after differentiation for either 18 (d18) or 25 days (d25).
This paper investigated acyl-ghrelin's ability to protect dopaminergic neurons in the substantia nigra pars compacta in a 6-OHDA lesion model of PD.
The focus of this chapter is to review work conducted on the functional assessment of animals following transplantation of hPSC-derived MSNs. We discuss different ways that graft function has been assessed, and the results that have been achieved to date.
This study used established and novel tasks to probe different aspects of irritable and impulsive behaviour to determine the neural mechanisms involved.
Different depression: motivational anhedonia governs antidepressant efficacy in Huntington’s disease
We used complementary approaches to determine treatment choice for depression in Huntington’s disease.
Here, we consider some outstanding questions on neural transplants for PD, including our understanding of the interaction between anti-Parkinsonian medication and the neural transplant, the impact of the cell therapy on cognitive or neuropsychiatric symptoms of PD, the role of neuroinflammation in the therapeutic process and the development of graft-induced dyskinesias.
We examined a single nucleotide variant, rs79727797, on chromosome 5 in the TCERG1 gene and its invovement in age of onset of the disease.
We review therapies targeting HTT DNA or RNA including recent results of trials using antisense oligonucleotides (ASO) followed by strategies targeting other disease mechanisms such as DNA repair, or downstream effects of mHTT protein.
This paper discusses whether advanced therapeutic medicinal products have the potential to impact a broader range of symptoms than just motor impairments, with a specific focus on the DA-dependent cognitive impairments in PD.
We assessed WM changes in premanifest HD by exploiting ultra‐strong‐gradient magnetic resonance imaging (MRI).
In this study, we used exome sequencing of 683 patients with HD with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect.
We investigated a general solution by introducing carbene chemistry to the field of nuclear imaging with a [18F]difluorocarbene reagent capable of a myriad of 18F-difluoromethylation processes.
Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington’s disease as a specific example, and suggest potential strategies to address these challenges.
This study investigated the cause of graft‐induced dyskinesias in in a rat model of PD.
In this paper we ask if foetal tissue transplantation continues to be justified in HD research.
In this paper we summarise data showing how the deprivation of either oxygen, glucose, or both in combination, impacts the survival of neurons and review strategies which may improve graft survival in the central nervous system.
This paper analyses white matter changes in the healthy and HD brain at multiple disease stages.
This paper asseses the prevalence, timing, and functional impact of psychiatric, cognitive, and motor abnormalities in Huntington disease (HD) gene carriers, we analyzed retrospective clinical data from individuals with manifest HD.
We describe two patients with Huntington's disease in whom the diagnosis of traumatic spinal cord injury was delayed, discuss the role that cognitive bias and other factors played in this delay, and the lessons we can learn.
Here we begin exploring the possibility that induced pluripotent stem cells (iPSC) derived from WGE may retain an epigenetic memory of their tissue of origin, which could enhance their ability to differentiate into STR cells.
The study set out to prove whether injectable microscale hydrogel scaffolds, containing heparin as a building block and affinity center, could act as a sustained delivery device to polarize macrophages and microglia towards the pro-regenerative M2 phenotype in the brain.
This review aims to summarize the preclinical and clinical studies of cell therapies in PD and HD. In addition, the precautions and strategies to ensure the highest quality of cell grafts, the lowest risk during transplantation and the reduction of a possible immune rejection will be outlined.
The CogTrainHD study assessed the feasibility and acceptability of home-based computerised executive function training, for people impacted by HD.
The objective of this study was to determine whether a single session of exercise was sufficient to induce cerebral adaptations in individuals with Huntington's disease and to explore the time dynamics of any acute cerebrovascular response.
This study compared DAergic transplants derived from two progenitor cell sources in an allograft system: mouse epiblast stem cells (EpiSC) and primary fetal mouse VM tissue.
This study's objective was to examine the relationship between hypertension and disease severity and progression in Huntington's disease.