Advantage and Core Benefit
- Expected to have an ameliorative effect on vascular remodeling
- A companion diagnosis is possible because elevated Myl9 levels in blood were observed in clinical.
Background and Technology
Pulmonary hypertension (PH) is an intractable disease in which blood pressure in the pulmonary artery is abnormally elevated. Although vasodilators are the principal treatment, there is still no drug that treats the vascular remodeling.
Myosin light chain (Myl) 9 is released from activated platelets during inflammation and forms net structures (Myl9 nets) in the vascular lumen. Inflammatory immune cells expressing CD69 infiltrate into tissues from blood vessels by using Myl9 nets as scaffolds (CD69-Myl9 system). Indeed, anti-Myl9/12 antibody that inhibits the binding of Myl9 to CD69 showed therapeutic effects on mouse models of asthma and IBD.
The inventors found the high Myl9 expressions in thrombi and the vascular endothelium in the lung of patients with PH as well as in those of a mouse model. Serum levels of Myl9 in patients with PH were elevated in correlation with disease severity. A patient case showed the reduction of serum Myl9 levels as symptoms improved with drug intervention.
When anti-Myl9/12 antibody was administered to PH mouse model, the therapeutic effects were comparable to those of tadalafil (PDE5 inhibitor). Furthermore, antibody administration inhibited the aberrant proliferation of vascular endothelial cells. Thus, anti-Myl9/12 antibody can be a new therapy for PH.
Data
- Myl9 deposition in mouse models of PH and in microthrombi in pulmonary arteries of patients with PH (A)
- Right ventricular systolic pressure and weight ratio of right ventricle to left ventricle (B) and observation of αSMA positive vascular endothelial cells (C) when anti-Myl9/12 antibody, control antibody or tadalafil (PDE5 inhibitor) were administered to PH mouse model.
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Patents
Basic patent: JPA 2022-165838, Substance patents on antibodies: US10513561, EP3404040, etc.
Researcher
Drs. Chiaki Iwamura and Sachiko Kuriyama (Chiba University)
Current Stage
- Myl9/12 humanized antibodies was established.
- We would like to proceed with clinical development after pre-clinical.
Expectations
We are interested in partnering with pharmaceutical and biotech companies that are interested in developing therapeutic antibodies for pulmonary hypertension based on the anti-Myl9/12 antibody established at Chiba University.
Project.WL-04637a