Customize ttr-5 Antibody

Description

T24/RT24 Antibody Series

Target: Residues 118–122 of human TTR (cryptic epitope).
Function:
- Inhibits TTR fibrillization at substoichiometric concentrations ([IC₅₀] ~50 nM) .
- Promotes macrophage phagocytosis of TTR aggregates via Fcγ receptor engagement .
Clinical Data: Reduced amyloid deposits in transgenic rat models (p < 0.05 vs. controls) .

NI301A Antibody

Target: Linear WEPFA epitope hidden in native TTR.
Function:
- Removes cardiac amyloid ex vivo by recruiting phagocytic immune cells .
- No cross-reactivity with physiological TTR tetramers .

Clone 2T5C9

Target: Mid-region epitope on TTR aggregates.
Applications:
- ELISA capture of soluble TTR aggregates (EC₅₀ = 2.0 µg/ml) .
- Immunohistochemistry (IHC) staining of amyloid deposits in formalin-fixed tissues .

Comparative Performance of Anti-TTR Antibodies

Antibody	Epitope	Target Species	Key Clinical Finding	Phase
T24	Residues 118–122	Human	40% reduction in tissue TTR deposits (rat)	Preclinical
NI301A	WEPFA motif	Human	Cleared 70% of cardiac amyloid ex vivo	Preclinical
2T5C9	Mid-region	Human	Detects soluble aggregates in serum (ELISA)	Research

Challenges and Opportunities

Specificity: Most antibodies (e.g., RT24, NI301A) avoid binding native TTR tetramers, minimizing off-target effects .
Delivery: CRISPR-based therapies (e.g., NTLA-2001) show promise but require long-term safety data .
Biomarker Utility: Anti-TTR antibodies like clone 2T5C9 enable quantification of circulating aggregates, aiding early diagnosis .

Future Directions

Next-generation anti-TTR antibodies are being optimized for:

Dual Epitope Targeting: Combining fibril-specific and monomer-neutralizing paratopes.
Half-Life Extension: Fc engineering (e.g., YTE mutations) to reduce dosing frequency .
Companion Diagnostics: Pairing therapeutic antibodies with ELISA/IHC assays for real-time monitoring .

Product Specs

Buffer

Preservative: 0.03% Proclin 300
Composition: 50% Glycerol, 0.01M Phosphate Buffered Saline (PBS), pH 7.4

Form

Liquid

Lead Time

Made-to-order (14-16 weeks)

Synonyms

ttr-5 antibody; C40H1.5 antibody; Transthyretin-like protein 5 antibody

Target Names

ttr-5

Uniprot No.

Q03575

Target Background

Database Links

KEGG: cel:CELE_C40H1.5

STRING: 6239.C40H1.5

UniGene: Cel.10721

Protein Families

Nematode transthyretin-like family

Subcellular Location

Secreted.

Q&A

Here’s a structured, research-focused FAQ collection for the TTR-5 antibody, derived from scientific methodologies and data in the provided materials. Questions are categorized by complexity and include methodological guidance and experimental evidence.

Advanced Research Questions

How to resolve discrepancies between FPE assay and Western blot data in TTR-5 antibody efficacy studies?

Discrepancies may arise due to:

Assay sensitivity: FPE detects early tetramer stabilization, while Western blot confirms structural integrity (FIG. 8) .
Sample handling: TTR aggregation during processing alters Western blot band patterns (FIG. 7A–B) .
Method: Validate findings with orthogonal assays (e.g., ELISA for soluble TTR) and use fresh/frozen samples in triplicate.

What statistical methods are robust for analyzing longitudinal TTR stabilization data?

Mixed-effects models account for repeated measures (e.g., daily FPE assays over 12 days) .
Pharmacokinetic-pharmacodynamic (PK/PD) modeling links serum antibody levels (Cmax, AUC) to target engagement (FIG. 14) .

How to design a study evaluating TTR-5 antibody effects on serum TTR levels in ATTR-CM patients?

Cohort design: Randomize patients into placebo vs. treatment arms (e.g., 6:2 ratio) .
Endpoints:
- Primary: Serum TTR concentration (baseline vs. Day 28) measured via immunoturbidimetry .
- Secondary: Echocardiographic metrics (e.g., myocardial strain).
Blinding: Use third-party labs for blinded sample analysis (FIG. 32) .

Data Tables for Methodological Reference

Table 1: Dose-Response Relationships in Single Ascending Dose Cohorts

Dose (mg)	Peak Engagement (%)	Time to Cmax (hr)	AUC₀–24 (μg·hr/mL)
300	72 ± 8	4.5	1,200
800	89 ± 5	3.8	2,450
Data aggregated from FIGS. 6, 10, 12 .

Table 2: Serum TTR Normalization in ATTR-CM Patients

Treatment Group	% Patients with Normal TTR (Baseline)	% Patients with Normal TTR (Day 28)
Placebo	18%	20%
800 mg b.i.d.	15%	92%
From FIG. 32 .

Key Methodological Notes

Assay Validation: Include placebo controls (e.g., subjects 1, 7 in cohort 3) to baseline-correct FPE data .
Longitudinal Stability: Store serum samples at –80°C to prevent TTR degradation.
Data Contradiction: Reconcile PK/PD outliers by re-assaying metabolites (e.g., AG10 HCl vs. free base) .

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ttr-5 Antibody