A Monoclonal Antibody against Misfolded TDP-43 for Neurodegenerative Diseases without Perturbing Native TDP-43
TDP-O antibody is a selective conformational antibody specific for misfolded TDP-43 oligomers to combat ALS and TDP-43 proteinopathies.
Targeted indication
Amyotrophic lateral sclerosis (ALS), Frontal temporal dementia (FTD), Alzheimer’s disease (AD)..etc.
Status
Pre-clinical
Key features
- A monoclonal antibody specific to misfolded TDP-43
- Rescue motor neurons and motor behaviors in mice
Market
- ALS is a motor neuron disease that leads to death in 3 to 5 years after disease onset without effective treatment. The global market for ALS is estimated to be $547.2 million and the compound annual growth rate (CAGR) is 5.8%.
- The world dementia patients have reached >47 millions including FTD and AD that cover most of the clinical dementia cases.
MODE OF ACTION
TDP-O antibody is a selective conformational antibody specific for misfolded TDP-43 oligomers to combat ALS and TDP-43 proteinopathies.
TDP-43 proteinopathies were found in several severe neurodegenerative diseases including > 95% ALS, ~50% FTD, and ~30-60% AD patients. The inclusions found in the brain or spinal cord lesions are composed of poly-ubiquitinated and hyperphosphorylated TDP-43 aggregates.
EXPERIMENTAL RESULTS
TDP-O specifically targeting misfolded TDP-43 with high affinity but not native TDP-43.
The efficacy of the antibody in vivo was proven by intravenous (i.v.) delivery of TDP-O9 antibody in a short period of time in two ALS mouse models (at 9-10 month &13-15 month of age). The administration significantly increased motor neuron survival, improved motor behaviors, reduced ALS disease-like pathology.
I.v. delivery of TDP-O9 antibody in aged TDP-43 Q331K transgenic mice ameliorated motor function impairment and increased motor neuron survival.
- TDP-O antibody facilitates the TDP-43 oligomer detection in plasma of ALS, where ALS patients have elevated TDP-43 oligomers in plasma.
- TDP-O antibody facilitates neuropathology characterization in post mortem tissues of ALS, FTD, and AD.
INTELLECTUAL PROPERTY
SELECTED PUBLICATIONS
1. Nature Communications, 5:4824 (2014) doi: 10.1038/ncomms5824.
2. Annals of Neurology, 78(2):211-21. (2015) doi: 10.1002/ana.24431.
3. Nature Communications. 11: 5950 (2020) doi: 10.1038/s41467-020-19786-7.
4. TDP-43-oligomer specific monoclonal antibodies identify TDP-43 oligomers in ALS patients and rescue abnormality in ALS mouse models. Ready to submit.
BUSINESS OPPORTUNITY
License and/or Collaboration and Sponsored Research
CONTACT
service@biip-dcc.org