2018-858 NETRIN-1 PEPTIDES FOR THE TREATMENT OF PULMONARY HYPERTENSION

INTRO SENTENCE:

UCLA researchers in the Department of Anesthesiology & Perioperative Medicine have developed a treatment for pulmonary hypertension.

 

BACKGROUND:

Pulmonary hypertension (PH) is a devastating cardiovascular “cancer” with increased vascular resistance in the lung and chronic failure of the right heart. Common symptoms include: shortness of breath, fatigue, chest pressure or pain, and cyanosis. Idiopathic PH can occur in patients at young ages with an unknown mechanism of spontaneous origin and was estimated to affect 2 million people in the United States in 2018. PH can also develop consequent to other pulmonary diseases, including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis and other hypoxic conditions. The overall incidence rate of all cause PH is around 2-3% in the general population, which represents a large body of patients requiring novel treatments of the disease that have yet been available to effectively stop progression of the disease or reduce mortality.

 

Current treatments for PH come from four drug classes, the two most common beingendothelin receptor antagonists (ERA) and phosphodiesterase type 5 inhibitors (PDE-5). Although three available ERAs delay clinical worsening of PH, these drugs may cause hepatotoxicity and pulmonary edema., PDE-5 inhibitors have been placed under a safety warning and not recommended for use in young patients due to increased mortality with increasing doses.  Overall, the current treatments improve PH only to an extent without permanent reversal of pulmonary vascular remodeling.

 

INNOVATION:

UCLA researchers have discovered a novel treatment for pulmonary hypertension. In their study, netrin-1 and netrin-1 peptides were demonstrated to treat pulmonary hypertension effectively for the first time. The mean pulmonary artery pressure and right ventricular systolic pressure were reduced up to 100% by netrin-1 and netrin-1 derived peptides V1, V2, and V3 in a hypoxia-induced pulmonary hypertension mouse model. The therapeutic agent may be chemically synthesized, or recombinantly expressed in a cell system or a cell-free system. Furthermore, the composition can be administered by any suitable route, including oral, transdermal, subcutaneous, intranasal, inhalation, intramuscular, and intravascular administration. The efficacy and flexibility have allowed different possibilities of commercialization of this novel therapeutic for pulmonary hypertension.

 

POTENTIAL APPLICATIONS:

•       Novel treatment for pulmonary hypertension

 

ADVANTAGES:

•       Significantly reduced mean pulmonary artery pressure and the right ventricular systolic pressure by 100% in a hypoxia-induced pulmonary hypertension mouse model

•       Can be chemically synthesized, or recombinantly expressed in a cell system or a cell-free system

•       Can be administered by any suitable route, including oral, transdermal, subcutaneous, intranasal, inhalation, intramuscular, and intravascular administration

 

DEVELOPMENT-TO-DATE:

This invention has been synthesized and tested in vivo in a hypoxia-induced pulmonary hypertension mouse model.

Patent Information: