Pipeline / 03 · Neuro & Oncology

Huntington's Disease Program

Precision neurotherapeutic strategies and molecular disease modeling for a monogenic disease with no current cure.

GENETIC CERTAINTY · HTT CAG EXPANSION The mutation is known decades before symptoms. TYPICAL AGE OF ONSET (YEARS) CAG REPEAT COUNT 40 45 50 55 60 20 30 40 50 60 HD threshold: ≥ 40 repeats
The HTT CAG-repeat expansion has a predictable, well-characterized relationship with age of onset. The mutation is known decades before symptoms appear — the therapeutic opportunity is to act within that window.
Premise

The problem we are solving.

Huntington's disease is one of medicine's cruelest inheritances — a single CAG-repeat expansion in the HTT gene that guarantees the disease's arrival, often decades before symptoms appear. Current therapies manage symptoms; none alter the underlying course.

The genetic certainty of Huntington's is also its therapeutic opportunity. The mutation is known. The protein is known. The pathogenic mechanism — toxic gain of function from the expanded mutant huntingtin protein — is increasingly understood. What remains is the engineering: a therapy that lowers mutant HTT in the brain, safely, durably, and at the right point in the disease course.

Approach

How we tackle it.

The Huntington's program integrates two of MACRO HRD's core capabilities: brain-mapping platform technologies for biomarker discovery and disease-progression staging, and BBB-facilitating delivery systems developed for the GBM Immunotherapy program. The strategic intent is precision neurotherapeutic design — matching intervention timing and modality to where each patient sits in the molecular disease course.

GEDM-3DQ provides the longitudinal modeling layer: tracking individual disease trajectories against multimodal biomarker signals, identifying intervention windows, and supporting the kind of adaptive trial design that monogenic disorders with long prodromal phases demand.

MULTIMODAL TRAJECTORY MODELING Decades of signal, one patient trajectory. GENOMICS HTT CAG count NEUROIMAGING Striatal volume FLUID BIOMARKERS Neurofilament light, mHTT CLINICAL STAGING Motor, cognitive, psychiatric GEDM-3DQ TRAJECTORY MODELING INDIVIDUAL TRAJECTORY intervention window DECADES · TIME
GEDM-3DQ integrates genomic, neuroimaging, fluid biomarker, and clinical staging signals into a patient-specific trajectory model — identifying the intervention window individually, not on population averages.
Capabilities

What makes this real.

01
Genetic precision targeting
Therapeutic strategies designed for the known molecular target — mutant HTT — rather than downstream symptom management.
02
BBB-facilitating delivery
Leverages AH-D peptide and lipid-nanoparticle delivery technologies developed for the GBM program for central nervous system access.
03
Disease-trajectory modeling
GEDM-3DQ longitudinal modeling identifies individual intervention windows from prodromal biomarker signals, decades before clinical symptom onset.
04
Brain-mapping integration
Co-developed with the Brain Mapping Platform — biomarker discovery and validation against the molecular disease landscape.
⸻ Continue the platform

“When a disease is genetically certain, intervention can begin before symptoms — if we know when, and how.”