aaRS-linked CMT

The CHARGE Study

Charcot-Marie-Tooth Hereditary Aminoacyl-tRNA synthetase Gene Registry

A natural history study spanning the largest single group of genes linked to CMT

Conducted by the Hereditary Neuropathy Foundation through the GRIN Registry

CHARGE is HNF’s natural history study spanning the aminoacyl-tRNA synthetase (aaRS) gene family: GARS1, YARS1, AARS1, HARS1, WARS1, MARS1, KARS1, and SARS1. Together they make up the largest single group of genes linked to CMT. These genes share a common biology. Each one “charges” tRNA with amino acids during protein synthesis, and disruption of that shared pathway, including activation of the cell’s stress response, is now understood to drive nerve damage across this entire subtype family.

One mechanism, many subtypes

Individually, each of these subtypes is rare enough that it would struggle to justify a study of its own. Taken together they are not rare at all, and they break in the same place. That is the whole idea behind CHARGE: by collecting data across every aaRS-linked subtype in one coordinated effort, the study fuels industry research targeting the shared mechanism, accelerating the path to treatments that could benefit patients across multiple rare CMT subtypes at once.

The eight genes

If your genetic report names any of these, CHARGE is for you. The subtype column shows the designation each gene is usually listed under, which you can also find in the full subtype index.

How it works

Four phases, built so that each one adds to what came before.

1. I Join and share your story Join GRIN, HNF’s Global Registry for Inherited Neuropathies, and complete your patient journey profile. Upload your genetic report if you have one. This is the foundation. Every phase after this builds on what you share here.
2. II Biospecimen collection Once enrolled, an HNF/GRIN co-investigator will contact you to arrange a biospecimen collection. At-home collection is currently available for participants in the United States. International participants: we do not yet have a solution for at-home collection outside the U.S., but you can still donate samples in person at either of our upcoming Summits (see Phase III), and we are actively working on how to extend remote collection globally.
3. III Join us at the annual CMT Clinical Trial Readiness Summit CHARGE participants, including international participants unable to access at-home collection, are invited to attend HNF’s Annual CMT Clinical Trial Readiness Summit, where standardized outcome measures are collected in person for the first time for aaRS-linked subtypes. This includes pilot studies using FDA-registered wearable devices to objectively assess gait, balance, fall risk, mobility, and upper limb function, alongside blood and urine sample donation to the CMT Biobank. The upcoming Summits are April 2027 and April 2028.
4. IV Longitudinal follow-up at the Summit Participants return to the Summit year over year for reassessment, combining in-person clinical measures with the ongoing real world data collected between visits, building the first longitudinal natural history dataset for aaRS-linked CMT subtypes and the exact evidence industry needs to design and qualify future clinical trials.