Huntingtin (HTT) Drug Discovery Landscape & Assay Solutions

TarMart Solution Ecosystem & Related Targets

Comprehensive reagent toolkit for Huntingtin drug discovery. Select your modality below:

Component / Network Product Description Product Link
Antigen (Wild-Type) HTT N-terminal (1-588) WT Control (Q23); also Exon-1 WT 23Q available. High purity (>95%), Endotoxin <1EU/µg. Sequence Verified. View HTT Products
Antigen (Mutant) HTT N-terminal (1-588) PolyQ Mutant variants (Q73, Q103); also Exon-1 Mutant 73Q. High purity (>95%), Endotoxin <1EU/µg. Sequence Verified by MS. View HTT Products
Gene Delivery HTT Promise-ORF / Lentivirus particles for full-length ORF (WT or Mutant exon-1). Ready-to-transduce for stable cell lines. View HTT Products
Benchmark Ab Anti-HTT recombinant monoclonal (MW7 epitope) for aggregate detection. Sequence-verified positive control. View HTT Products
Validator HTT siRNA Set (3 unique sequences). For allele-selective or total knockdown verification. View HTT Products
Related Target: BDNF Brain-Derived Neurotrophic Factor – neurotrophic support disrupted by mHTT. View BDNF Products
Related Target: mTOR Mechanistic Target of Rapamycin – autophagy-mediated clearance of mHTT aggregates. View mTOR Products
Related Target: ATXN3 Ataxin-3 – polyQ aggregation model, autophagy overlap. View ATXN3 Products
Related Target: ATXN1 Ataxin-1 – comparative polyQ disease target. View ATXN1 Products
Related Target: TFEB Transcription Factor EB – master regulator of autophagy-lysosome pathway. View TFEB Products
Related Target: VCP Valosin-containing protein – involved in protein clearance and aggresome formation. View VCP Products
Critical Assay Challenge The TarMart Advantage (Technical Spec)
Allele-selective mutant vs WT discrimination Precise PolyQ length variants (Q23, Q73, Q103) with Mass Spec verified MW; WT (23Q) and Pathogenic (73Q/100Q) Exon 1 proteins with >95% purity.
Aggregate-prone protein handling & solubility Endotoxin controlled (<1 EU/µg); low-endotoxin formulation prevents artifactual aggregation in neuronal assays.
Cross-species preclinical safety (Cyno/Mouse) Human / Mouse / Cyno ortholog proteins available with sequence identity >95%.
Intracellular delivery validation Ready-to-transduce Lentivirus particles for neuronal lineage stable expression.
Off-target specificity control Validated siRNA included for HTT-specific vs non-specific toxicity differentiation.
Knockdown validation & controls Validated siRNA included for HTT specificity checks and protein lowering validation.

Live HTT R&D Tracker

Market data changes daily. Access the latest global pipeline status directly:

Global Clinical Landscape & Future Outlook

The therapeutic landscape for Huntington's disease (HD) is pivoting from non-selective gene silencing toward precision allele-selective strategies following the discontinuation of first-generation total HTT lowering therapies. Current R&D focuses on distinguishing mutant from wild-type huntingtin to preserve essential physiological functions while selectively clearing toxic polyQ-expanded proteins. Major players include Wave Life Sciences (allele-specific ASO WVE-003), uniQure (AAV-delivered microRNA AMT-130), and Novartis/PTC Therapeutics (small molecule splicing modulators). The next wave emphasizes mutant-specific protein clearance via PROTACs and autophagy enhancers targeting intracellular aggregate clearance.

Competitive Modality & Indication Snapshot

Modality Representative Players Key Indications Critical Assay Need (Why TarMart?)
ASO / Gene Silencing Roche/Ionis, Wave Life Sciences Huntington's Disease Allele-selective screening (Need Mutant vs WT proteins); knockdown validation (Need siRNA & lentivirus)
siRNA / RNAi Alnylam, Arrowhead Neurodegeneration Intracellular uptake validation (Lentivirus stable lines)
Small Molecule (Splicing & Lowering) Novartis (Branaplam), PTC Therapeutics Huntington's Disease Aggregation inhibition assays (High-purity mutant protein); splicing modulation assay
PROTAC / Targeted Degradation Arvinas, Novartis Huntington's Disease Intracellular target engagement (Need stable cell line lentivirus)
Gene Therapy (AAV) uniQure, Voyager Therapeutics Huntington's Disease (CNS delivery) Expression level standardization (Benchmark Abs); specificity validation (Need WT vs Mutant ORF)

Key Mutations and Target Identity

The target requested (Huntingtin/HTT) resolves to the HTT gene (UniProt P42858). Key mutations reported include:

  • D550 proteolytic cleavage inhibition: Mutation at residue D550 inhibits proteolytic cleavage and abolishes post-translational myristoylation (UniProt VAR_081737).
  • LOMARS variant: dbSNP rs768047421, associated with a specific disease-related polymorphism.
  • rs363075: A common SNP in the HTT gene (dbSNP rs363075).

These mutations underline the importance of allele-specific reagents and assays to discriminate between wild-type and mutant HTT.