The process of heart failure
Heart failure results from the heart’s inability to maintain sufficient cardiac output to meet the metabolic demands of the body. It The progression of cardiac hypertrophy represents the principal risk factor for the development of heart failure and subsequent cardiac death. Cardiac hypertrophy is classically considered to be an adaptive and compensatory response that increases the work output of cardiomyocytes and thus maintains cardiac function despite increased load. Increased resistance, created by pathology such as hypertension, initially compromises left ventricular (LV) function. Subsequently the development of LV hypertrophy begins to restore systolic function, and concentric LV hypertrophy develops, which increases the LV mass. A decline in LV function accompanies LV chamber dilation, apoptosis, myocardial fibrosis and tissue remodeling, which results in eventual HF and death.
Unmet, urgent need for new therapies.
There are significant gaps in the therapeutic options for Heart Failure. HF is categorized into two subsets based on left ventricular ejection fraction (LVEF). Heart failure with reduced ejection fraction (HFrEF) is generally described as LVEF of <40%, and heart failure with a preserved ejection fraction (HFpEF) is defined as LVEF >50%, although there are some ranges and variation in the literature around these definitions. Following diagnosis, patients are also grouped into one of four classes based upon their symptom status. New York scales I-IV (based on physical activity) and American College of Cardiology/American Heart Association Stages A-D based on symptoms and structural changes are used to group patients and define eligibility for therapeutic regimens.
Several areas of unmet need that are priorities have been identified:
(i) Therapies that specifically target HFpEF;
(ii) Therapies that reverse heart damage rather than just slow disease progression;
(iii) Therapies that can be used safely in patients with multiple medical comorbidities; and
(iv) Medications used in the setting of acute HF exacerbation.
Makai Biotechnology offers novel heart failure therapy through TRPV1 agonist-mediated desensitization or antagonism. Our ground-breaking studies demonstrate effectiveness of targeting TRPV1 to meet currently unmet therapeutic needs.