Kleopas A. Kleopa and Daniela Menichela- SPC co-Chairs

Content Disclaimer:  The suggestions listed below are that of the PNS Scientific Program Committee Co-Chairs & do not represent the opinions of the PNS Board, nor the Society as a whole.

1. Novel technologies and ideas have emerged to understand pathomechanisms at single cell level, genetic causes, create innovative models, and test therapeutics for neuropathies:

• single cell RNAseq and spatial transcriptomics, lipidomics and bulk RNA-sequencing
• innervated skin on a chip model
• Organoid models of myelination
• iPSCs
• Long read sequencing and structural DNA variations

TO DO: These are currently limited to certain models and types of neuropathies. Need to be taken up by all SIGs, from bench to bedside, in a multidisciplinary approach to improve diagnosis and treatment of all neuropathies with clinical applications

2. Novel Imaging approaches and biomarkers, innovative trial design for peripheral nerves and neuromuscular system

• FINEscope imaging of intraepidermal fibers
• Novel ultrasound methods (Shear Wave Elastography Imaging, Photoacoustic Imaging, Artificial Intelligence)
• Biomarkers (tau, NFL, imaging)
• Sensitive clinical outcome measures
• Complexity of trial design: patient selection, disease duration and activity

TO DO: Further validation of diagnostic accuracy across neuropathy types and against traditional invasive methods still needed. Longitudinal evaluations of biomarkers mostly lacking, natural history studies highly needed across neuropathies

3. Emerging new therapies for inherited and acquired neuropathies

• New targets for therapeutic genome editing
• Gene editing, gene silencing, gene replacement all applied to neuropathies
• Viral and non-viral gene therapies progressing through pre-clinical development
• Novel immunological therapies for autoimmune neuropathies
• Novel drug-based approaches, some entering clinical trials

TO DO: Need to evaluate position of new therapies for each neuropathy type, bridge the gap to clinical translation, prioritize clinical trials, address rare neuropathies, develop guidelines for monitoring and treatment

Proposed goals for the PNS community to achieve the goals above

• Enhance SIG interaction, incorporate new technologies (imaging, transcriptomics) into clinical trials for all PNs, harness them towards precision medicine, measure treatment response (biomarkers)
• Facilitate exchange between basic scientists and clinicians, make available clinical material (tissues, cells) from well-characterized patients for molecular study, iPSCs across SIGs
• Coordinated therapeutics development and evaluation, organize disease-focused treatment working groups to coordinate, prioritize, develop, and critically evaluate new treatments

Suggestions for implementation in the coming year

• Create multidisciplinary working groups around the 3 basic topics (novel technologies, imaging tools, trial design) with representatives from all SIGs and between basic scientists and clinicians
• Within each SIG establish neuropathy-type working groups for therapeutics development, assess current progress, identify priority areas, and advocate for translation, clarify position of each Tx in the clinic
• Send survey after the meeting with questions to potential participants in each working group
• SIGs to coordinate the establishment of the groups
• Once established, working groups will set SMART goals and plan meetings
• Each working group to present their SMART goals and report progress at 2024 PNS in Montreal!