Invention:
This invention is a targeted peptide conjugated with an antioxidant to inhibit Akt1 nitration. It can be utilized for treating pulmonary arterial hypertension (PAH) with potential application in other abnormal proliferative disorders such as cancer.
Background:
Pulmonary arterial hypertension (PAH) is a disorder affecting 1.1 to 17.6 million adults per year with a prevalence of 6.6 to 26 million. This progressive disorder is characterized by angioproliferative vasculopathy in the pulmonary arterioles leading to endothelial and smooth muscle proliferation, dysfunction, inflammation and thrombosis.
The pathology of the disorder is associated with the thickening/remodeling of the pulmonary artery wall. The Atk1 (Protein Kinase B) serine/threonine kinase pathway plays an important role in normal and pathological vascular development and functioning as well as in other cellular functions such as glucose metabolism, cell proliferation, apoptosis, cell migration and transcription. Increased activation of the Atk1 signaling pathway is believed to play a role in PAH pathophysiology through inhibition of apoptotic signaling and promotion of cell survival.
Currently the disease remains incurable despite existing therapies which are largely ineffective. Patients are therefore limited to invasive heart-lung transplantation which is only available in limited surgical centers worldwide and which has only a 50% survival rate at 5 years. Thus, the present invention is a targeted peptide conjugated with an antioxidant, that acts as an inhibitor at the Atk1 nitration site associated with PAH pathological conditions.
Applications:
- Targeted treatment for PAH and other proliferative disorders
Advantages:
- Significant need
- Few alternative effective therapies currently available
- Targeted selectivity for Atk1 nitration (i.e will not affect Atk1 phosphorylation and thus affect other physiological processes controlled by Atk1 signaling pathways)
- Potential for greater applications beyond PAH to also include other proliferative disorders
