MIGLIORE ARTICOLO DEL MESE CON PRIMO AUTORE ITALIANO

“Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic
Patients: The AMYPAD-DPMS Randomized Clinical Trial”

Daniele Altomare, Frederik Barkhof, Camilla Caprioglio, et al.

JAMA Neurol. 2023 Jun 1;80(6):548-557.
Link: Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients: The AMYPAD-DPMS Randomized Clinical Trial - PubMed (nih.gov)

Selezionato dal lettore: Dott.ssa Ilaria Quartesan

MOTIVATION: Amyloid deposition in the brain is a key hallmark of Alzheimer's disease (AD), and amyloid PET tracers have enabled the direct assessment of amyloid deposition in vivo. Despite the increasing use of amyloid PET in clinical practice, there is still limited real-world evidence regarding its clinical utility and cost-effectiveness.

The article presents the findings of the Amyloid Imaging to Prevent Alzheimer's Disease Diagnostic and Patient Management Study (AMYPAD-DPMS), a prospective, multicenter, randomized clinical trial designed to assess the clinical utility and cost-effectiveness of amyloid PET in memory clinic patients. The researchers compared three study groups: one group underwent early amyloid PET, another group underwent late amyloid PET, and the third group had unrestricted amyloid PET based on the managing physician's choice. The main outcome measured was the proportion of participants receiving an etiological diagnosis with high diagnostic confidence (≥90%) after 3 months. Secondary outcomes included changes in diagnosis, diagnostic confidence, and treatment plans. The study found that participants who underwent early amyloid PET had a significantly higher proportion of receiving an etiological diagnosis with high diagnostic confidence compared to those who had not yet undergone amyloid PET (40% vs. 11%). This effect was consistent across different cognitive stages (subjective cognitive decline, mild cognitive impairment, and dementia). The study also showed that amyloid PET resulted in changes in etiological diagnosis and increased diagnostic confidence.

Overall, the AMYPAD-DPMS contributes to the evidence gap regarding the clinical utility and cost-effectiveness of amyloid PET. The findings support the widespread implementation of amyloid PET in the diagnostic evaluation of patients with cognitive decline, as it enables early and confident diagnosis, facilitates appropriate management decisions, and potentially improves patient outcomes.

MIGLIORE ARTICOLO DEL MESE IN ASSOLUTO

“AAV5-miHTT-mediated huntingtin lowering improves brain health in a Huntington’s disease mouse model”

Sarah B Thomson, Anouk Stam, Cynthia Brouwers, Valentina Fodale, Alberto Bresciani, Michael Vermeulen, Sara Mostafavi, Terri L Petkau, Austin Hill, Andrew Yung, Bretta Russell-Schulz, Piotr Kozlowski, Alex MacKay, Da Ma, Mirza Faisal Beg, Melvin M Evers, Astrid Vallès, Blair R Leavitt

Brain, Volume 146, Issue 6, June 2023, Pages 2298–2315
DOI: https://doi.org/10.1093/brain/awac458  

Selezionato dal lettore: Dott.ssa Benedetta Draià

MOTIVATION: In this cross-sectional study, the authors explored a therapeutic pathway to treat Huntington’s disease using a new-developed microRNA targeting human HTT that is delivered in an adeno-associated serotype 5 viral vector (AAV5-miHTT), delivered in a homozygous Q175FDN mice, a mouse model of Huntington’s disease with severe neuropathological and behavioural phenotypes, through a bilateral intrastriatal injection of two different doses. The aim was to test the effect of this HTT-lowering therapy on weight loss, motor deficits, protein expression in plasma and CSF, regional brain volum loss, striatal metabolites and transcriptional dysregulation. High dose AAV5-miHTT resulted in a highly efficient, 65.8% reduction of mutant HTT in striatum and a 29.8% reduction of mutant HTT in cortex. This pattern of mutant HTT lowering rescued weight loss, significantly increased regional brain volume in the hippocampus, improved biochemical metabolite profiles associated with neuronal damage as measured by in vivo H-MRS, and partially reversed mutant HTT-associated transcriptional dysregulation in homozygous Q175FDN striatum. The results of this study support HTT-lowering therapy using AAV5-miHTT as a promising strategy for Huntington’s disease treatment and provide evidence for the utility of H-MRS as a non-invasive imaging modality in HTT-lowering clinical trials.