A small South San Francisco team chasing one stubborn protein - and betting it can change the math on ALS.
In a lab in South San Francisco, the whole company fits in a room. About twenty-one people. No blockbuster on the market, no decades of history, no comfortable cushion of legacy revenue. What Trace Neuroscience has instead is a conviction sharp enough to organize everything else around it: that most of ALS traces back to one protein going missing - and that the protein can be put back.
That protein is UNC13A. In a healthy nervous system it sits at the synapse, the gap where a motor neuron hands its instructions to a muscle. It is the handshake between nerve and muscle. In amyotrophic lateral sclerosis, that handshake fails. The muscles stop receiving the message. The body, gradually, stops answering.
For years the field treated ALS as maddeningly heterogeneous - a hundred small fires rather than one. Trace's wager is the opposite. Roughly 97% of people with ALS show the same molecular failure upstream of UNC13A, which is an unusually large slice of any disease to address with a single idea.
The mechanism reads almost like a detective story. A protein called TDP-43 normally supervises how the cell edits its genetic messages - which bits of RNA get kept, which get spliced out. When TDP-43 falters, the editing goes wrong. A stray "cryptic" exon sneaks into the UNC13A message. The faulty message never becomes working protein. The synapse goes quiet. Trace's job is to intercept that bad edit before it does its damage.
Its tool is an antisense oligonucleotide - a short, designed strand of genetic material called TRCN-1023. Delivered by intrathecal injection, straight into the spinal fluid, it binds to the UNC13A message and steers the splicing back toward the correct version. Restore the message, restore the protein, restore the handshake. That is the entire thesis, stated plainly.
The cell's RNA-editing supervisor loses its grip.
A cryptic exon slips into the UNC13A message.
No working UNC13A is made. The synapse weakens.
An ASO corrects the splice and restores the signal.
DIAGRAM: four steps, one target. The whole company is organized around interrupting the third box before it happens.
Bars are illustrative of scale, not to a shared axis. Figures from public launch disclosures, 2024-2026.
An antisense oligonucleotide for ALS, given by intrathecal injection. It binds UNC13A messenger RNA, corrects the mis-splice, and restores the protein that keeps nerve and muscle talking. Entered clinical development in 2026.
A genomic-medicine platform built around the TDP-43 to UNC13A axis - with a stated path beyond ALS toward frontotemporal dementia and Alzheimer's disease.
Cardiologist by training; helped build MyoKardia and Maze Therapeutics before turning to the brain.
Professor of Cellular & Molecular Neuroscience; helped surface UNC13A's role in ALS.
Professor of Genetics whose lab connected TDP-43 biology to the UNC13A insight.
Senior Investigator at the National Institute of Neurological Disorders and Stroke.
PORTRAIT, UNRETOUCHED: four careers that rarely share a hallway, pointed at the same synapse. Jeffrey Tong of Third Rock chairs the board.
The launch paired the cash with an exclusive license to the foundational UNC13A intellectual property from University College London - turning an academic finding into a clinical program in under two years.
Trace emerges with a $101M Series A led by Third Rock Ventures and an exclusive UNC13A license from UCL.
Named a Fierce Biotech "Fierce 15" Biotech Company of 2025 - an early industry vote of confidence.
Global clinical development of TRCN-1023 opens with a Phase 1/2 trial in the UK and the Netherlands.
An investigator-initiated trial in China begins with partner Tenacia Biopharmaceutical at Beijing Tiantan Hospital.
Return to that room in South San Francisco. The headcount has not ballooned. The hallway is still quiet. But the work has left the building - it is in clinics in three countries now, in spinal fluid, in patients who agreed to find out whether a single corrected splice can hold a synapse open a little longer.
Nothing about ALS is settled, and Trace is careful not to pretend otherwise. A genetically validated target is a strong starting hand, not a finished one. The trials will say what the biology cannot promise. But the company has done the harder, quieter thing first: it took a disease the field called scattered, and traced it back to one missing note.
A piano with one key restored does not become a symphony overnight. But it can play the chord again. That is the whole bet - and, for the first time, it is being tested on people rather than in slides.
Sources: company press releases, BusinessWire, BioSpace, Fierce Biotech, BioPharma Dive, C&EN, UCLB, Inside Precision Medicine. Figures approximate where noted.