Undisclosed Huntington’s disease therapeutic / Anima Biotech, Takeda - LARVOL DELTA

NFE2L1 as a central regulator of proteostasis in neurodegenerative diseases: interplay with autophagy, ferroptosis, and the proteasome. (PubMed, Front Mol Neurosci) - "Maintaining proteostasis is critical for neuronal health, with its disruption underpinning the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases...Furthermore, we discuss the pathological implications of NFE2L1 dysfunction and explore its potential as a therapeutic target. By highlighting gaps in the current understanding and presenting future research directions, this review aims to elucidate NFE2L1's role in advancing treatment strategies for neurodegenerative diseases."

Journal • Review • Alzheimer's Disease • CNS Disorders • Huntington's Disease • Movement Disorders • Parkinson's Disease

NOVEL DIGITAL MEASURES OF REACTION TIME AND DRAWING SPEED: A FEASIBILITY STUDY IN PATIENTS WITH NEURODEGENERATIVE DISORDERS AND IMMUNE MEDIATED INFLAMMATORY DISORDERS. (ADPD 2025) - "Aims: The IDEA -FAST consortium aims to further measurement of fatigue by capturing rich digital data from Parkinson's Disease, Huntington's Disease, and immune mediated inflammatory disorder (IMID) cohorts... In this small sample, measures of reaction time, movement time and vigilance, derived from brief digital assessments, may provide insights into the cognitive processes underpinning performance in different neurodegenerative diseases not evident in global a ccuracy measures."

Clinical • CNS Disorders • Fatigue • Huntington's Disease • Inflammation • Movement Disorders • Parkinson's Disease

Study protocol for the iMarkHD study in individuals with Huntington's disease. (PubMed, J Huntingtons Dis) - " By combining PET and multi-modal MRI assessments we expect to provide a comprehensive examination of the molecular, functional, and structural framework of HD progression. As such, the iMarkHD study will provide a solid base for the identification of treatment targets and novel outcome measures for future clinical trials."

Biomarker • Journal • Developmental Disorders • Huntington's Disease • Movement Disorders

Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure. (PubMed, Nat Commun) - "Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington's disease (HD)...Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD."

Journal • CNS Disorders • Huntington's Disease • Movement Disorders

Evaluation of walking activity and gait to identify physical and mental fatigue in neurodegenerative and immune disorders: preliminary insights from the IDEA-FAST feasibility study. (PubMed, J Neuroeng Rehabil) - "Counterintuitively, the outcomes indicate that there is a weak relationship between typical gait measures and abnormal fatigue. However, factors such as the COVID-19 pandemic may have impacted gait behaviours. Therefore, further investigations with a larger cohort are required to fully understand the relationship between gait and abnormal fatigue."

Journal • CNS Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Huntington's Disease • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Lupus • Movement Disorders • Novel Coronavirus Disease • Parkinson's Disease • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus

Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington's disease. (PubMed, J Biomed Sci) - "Our findings reveal early cortical resting-state hyperperfusion and impaired CVR at ages that present motor anomalies in this HD model, suggesting that further characterization of brain perfusion alterations in animal models is warranted as a potential therapeutic target in HD."

Journal • Preclinical • CNS Disorders • Huntington's Disease • Movement Disorders

Generation of an induced pluripotent stem cell line from a Huntington's disease patient with a long HTT-PolyQ sequence. (PubMed, Stem Cell Res) - "Reprogrammed iPSCs expressed pluripotency-associated markers, exhibited a normal karyotype, and following directed differentiation generated cell types belonging to the three germ layers. PCR analysis and sequencing confirmed the HD patient-derived iPSC line had one normal HTT allele and one with elongated CAG repeats, equivalent to ≥180Q."

Journal • Preclinical • CNS Disorders • Huntington's Disease • Movement Disorders

Generation of induced pluripotent stem cells from three individuals with Huntington's disease. (PubMed, Stem Cell Res) - "The iPSC lines exhibited one healthy HTT allele and one with elongated CAG repeats, as confirmed by PCR and sequencing. All iPSC lines expressed pluripotency markers, exhibited a normal karyotype, and generated cells of the three germ layers in vitro."

Journal • CNS Disorders • Huntington's Disease • Movement Disorders

Recommendations to Optimize the Use of Volumetric MRI in Huntington's Disease Clinical Trials. (PubMed, Front Neurol) - "Here, we propose four recommendations to address vMRI standardization in HD research: (1) a checklist of standardized practices for the use of vMRI in clinical research and for reporting results; (2) targeted research projects to evaluate advanced vMRI methodologies in HD; (3) the definition of standard MRI-based anatomical boundaries for key brain structures in HD, plus the creation of a standard reference dataset to benchmark vMRI data analysis methods; and (4) broad access to raw images and derived data from both observational studies and interventional trials, coded to protect participant identity. In concert, these recommendations will enable a better understanding of disease progression and increase confidence in the use of vMRI for drug development."

Clinical • Journal • Review • CNS Disorders • Huntington's Disease • Movement Disorders • MRI

Mislocalization of Nucleocytoplasmic Transport Proteins in Human Huntington's Disease PSC-Derived Striatal Neurons. (PubMed, Front Cell Neurosci) - "Lowering total HTT using HTT-targeted anti-sense oligonucleotides partially restored gene expression, as well as subtly reducing mislocalization of proteins involved in nucleocytoplasmic transport. This suggests that mislocalization of RAN, RANGAP1 and lamin-B1 cannot be normalized by simply reducing expression of CAG-expanded HTT in the absence of healthy HTT protein."

Journal • CNS Disorders • Huntington's Disease • Movement Disorders

Volumetric MRI-Based Biomarkers in Huntington's Disease: An Evidentiary Review. (PubMed, Front Neurol) - "We also evaluate the relationship between imaging measures and clinical change, their longitudinal change characteristics, and within-individual longitudinal associations of imaging with disease progression. This analysis will be valuable in assessing pharmacodynamics in clinical trials and supporting clinical outcome assessments to evaluate treatment effects on neurodegeneration."

Biomarker • Journal • Review • CNS Disorders • Cognitive Disorders • Huntington's Disease • Mental Retardation • Movement Disorders • Psychiatry • MRI

[VIRTUAL] Anima Biotech (BIO 2021) - "Our pipeline includes programs in Fibrosis (tissue selective Collagen I translation inhibitors), Oncology (selective translation inhibitors of c-Myc and K-Ras), RSV (viral translation inhibitors), Huntington's disease (translation inhibitors of the mutant protein without affecting the wild type, extendable to a many Repeat Associated Diseases) and our $1B partnership with Lilly around several Neuroscience targets. Our science was further validated with 7 patents, 15 peer-reviewed publications, and 17 scientific collaborations."

Fibrosis • Huntington's Disease • Immunology • Movement Disorders • Oncology • Respiratory Syncytial Virus Infections • KRAS • MYC