Preclinical Development of CNM-Au8 as a Candidate Therapeutic for Amyotrophic Lateral Sclerosis
Abstract
Applicability of the Research Proposed: Amyotrophic lateral sclerosis (ALS) is a complex disease, the causes of which are still not well understood. While developing an effective drug for ALS has been extremely challenging, several recent studies have discovered a commonality shared by many individuals with ALS: hypermetabolism. When hypermetabolism is present in ALS, food is processed quickly but it is not converted into useful energy for the body. Because motor neurons have very high energetic needs in order to function, inefficient energy metabolism likely leads to their degeneration and death. Studies show that hypermetabolism is present in ALS patients before they show outward signs of the disease, and that higher levels of hypermetabolism predict worse outcomes. CNM-Au8 is a candidate drug for ALS that provides an energetic assist to diseased cells, helping them improve their energy stores in order to survive and function. Our early experiments with CNM-Au8 in disease models of ALS have shown that CNM-Au8 holds much promise as a new therapeutic for ALS. The long-term goal of this proposal is to confirm our early indications that CNM-Au8 is an effective candidate drug for the treatment of ALS. In addition, the proposed study expands our understanding of the types of ALS patients CNM-Au8 may best treat. Ultimately, the goal of our studies is to use these results to assist in the design of efficient, informative clinical trials for the demonstration of this drug s efficacy and safety, bringing this novel therapy as rapidly as possible to ALS patients in need. Types of ALS Patients That May Be Helped by CNM-Au8: Since sporadic ALS (sALS) represents about 90% of all cases of ALS, it is important to determine whether CNM-Au8 can treat sALS cells. We propose several ways to test whether CNM-Au8 treatment of sALS cells makes them energetically healthier. In addition, our collaborators have made an important discovery about a subpopulation of sALS patients, called sALS-1 patients. Blood samples from sALS-1 patients show an imbalance in energetic chemicals compared to other sALS patients (sALS-2). There is the possibility that CNM-Au8 will work especially well in helping sALS-1 cells survive stress because of the energy assistance it can give to these especially stressed cells. Therefore, we have proposed several ways to test whether CNM-Au8 is especially effective for sALS-1 patient cells. Results from these studies may indicate that sALS-1 patients may best benefit from CNM-Au8 treatment. sALS-1 patients can be easily identified using a blood test (described above). Including these patients in a clinical trial will streamline the process of achieving FDA approval for CNM-Au8 treatment of ALS. Potential Clinical Applications, Benefits, and Risks: The proposed mouse model study of CNM-Au8 will help determine if CNM-Au8 treatment can extend the lifespan and improve functions of ALS model mice. Results from this study will more clearly define the benefits we would expect to see in humans. Based on our earlier studies, we expect to see an extension of lifespan as well as improved motor functions in treated mice. An additional benefit of CNM-Au8 is that it is taken orally on a daily basis and therefore does not require hospital visits or infusions in order to be administered to have protective effects on the brain. Risks to patients have been mitigated to an extent through our long-term animal chronic toxicity studies and from our First-In-Humans Phase 1 Clinical Trial. The results of both these studies showed that CNM-Au8 is safe and well-tolerated in humans. Projected Timeline: The proposed study will take two years two complete; however, by early 2021, our Phase 2 Proof of Concept imaging study will also be complete. This study will show whether brain energy metabolites change in response to CNM-Au8 treatment. Positive results from the preclinical studies proposed here coupled with results from this Phase 2 study
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010166
Entities
People
- Karen Ho
Organizations
- Clene Nanomedicine Inc.
- United States Army