First-in-Class Peptidomimetic Drug for the Treatment of TBI and Sequelae: Nonclinical Safety Assessment
Abstract
Background: Traumatic brain injury (TBI) is the major cause of cognitive disability in the U.S. affecting 5.3 million Americans, including approximately a half a million Service Members and Veterans. Patients with TBI experience debilitating symptoms, such as memory loss, problems speaking or understanding language, anxiety, mood swings, and paralysis. Caregivers are also affected and may develop burn-out. Overall, the estimated economic costs of TBI exceed $79 billion annually. While therapeutic interventions such as surgery, drugs, and rehabilitation may lead to some degree of recovery, TBI-induced deficits are often permanent. A key reason current therapies fail to result in a complete recovery is that they do not counteract a TBI-induced accumulation of a powerful molecule in the brain that blocks recovery and regeneration of brain tissue. Several published studies have shown the potential benefit of blocking this molecule to spare brain tissue after injury in animal and cell-based studies. The clinical (human) benefits of blocking this molecule have not been realized because the molecular target has been considered to be undruggable due to its chemical characteristics. Conventional drugs are simply unable to engage the target molecule. We have developed a novel drug (A-456), a new class of drug, that has characteristics which allow it to block this target molecule and promote the survival and regeneration of brain tissue. We have shown that A-456 is effective at clinically relevant doses both in cellular and animal models of TBI. It is also very stable, and it is therefore a good candidate for oral administration. Objective: Our objective is to complete the nonclinical studies needed to submit an Investigational New Drug (IND) Application to the Food and Drug Administration (FDA) to support first-in-human dosing in under 2 years, bringing us closer to our goal of FDA approval for all patients by 2027. In short, A-456 is a transformative new class of drug that we believe can be administered orally to all TBI patients to improve cognitive function, reduce anxiety, and alleviate chronic pain, which are common in TBI patients. This project, therefore, addresses the FY22 TBIPHRP Focus Area Treat and the subareas Interventions that address neurodegenerative processes associated with TBI; Interventions that restore cognitive reserve and functioning; and Interventions and/or the delivery of healthcare services to improve the ability to treat co- occurring TBI and psychological health conditions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310451
Entities
People
- Edmund Nesti
Organizations
- United States Army