As society advances towards a healthier future, a key component in ensuring public health is the development of therapeutics to treat neurodegenerative diseases. Cutting-edge discoveries in nanotechnology hold enormous promise for combatting age-related neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease), and multiple sclerosis.
Clene Nanomedicine, a biopharmaceutical company focused on developing nanotherapeutics, used a patented manufacturing breakthrough to create CNM-Au8®, a gold nanocrystal suspension that has the unique ability to catalyze metabolic energy reactions. Dr. Karen Ho and her team at Clene began to consider the implications of CNM-Au8’s catalytic abilities to support and protect nervous system cells, which are put under stress in many neurodegenerative diseases. Dr. Ho’s project, “Nanocatalysis for the Improvement of Human Healthspan and Lifespan,” won the National Academy of Medicine’s Healthy Longevity Catalyst Award for its innovative approach to researching the implications of this new technology for those with Alzheimer’s disease.
The production process of CNM-Au8 creates highly faceted, clean surfaced gold nanoparticles without chemical surfactants or surface capping stabilizing agents, meaning that the nanocrystals that result are highly biologically active catalysts for cellular energy production. This feature of CNM-Au8 allows the surfaces of the particle to catalyze key metabolic reactions, such as the conversion of nicotinamide adenine dinucleotide (NADH) to its oxidized form, NAD+, which is unique in the field and important for neuron protection, repair, and survival. Neurons require high levels of energy in order to carry out their functions, and when energy deficits occur due to aging, environmental toxins, or genetic factors, neuronal death can result.
The Clene clean room where Dr. Ho and her colleagues create CNM-Au8
“While it has been known for some time that increasing NAD+, lowering oxidative stress, and addressing the toxicity of misfolded proteins can be effective and disease-modifying in models of neurodegenerative disease, CNM-Au8 is the first drug, to our knowledge, to address all three of these deficits at once using nanocatalysis,” Dr. Ho said. “Our study’s objective is to determine whether CNM-Au8 can help to treat or reverse some of the energetic changes that occur with both aging and Alzheimer’s disease. Alzheimer’s is a disease in which metabolic and energy-generating functions are severely challenged in the diseased brain. Our Healthy Catalyst Award study will help us gain important insights into the complex molecular pathology and energetic dysfunctions of aging, what aging and disease-related changes we must address in order to improve neuronal survival and function, and how we can design drugs like CNM-Au8 to address multiple points of failure at once to help improve patient outcomes. If successful, this would, indeed, be a breakthrough for aging, neurodegenerative diseases, and drug development.”
CNM-Au8 has already passed Phase I in the clinical trial process and has demonstrated no serious adverse reactions when orally consumed. Preclinical models have also shown the treatment to promote the survival of many different subtypes of neurons subjected to disease-relevant toxins and stressors, as well as remyelination of neurons and recovery of motor functions. Remyelination is beneficial for individuals with neurodegenerative diseases because the myelin sheath, which remyelination rebuilds after damage, helps to protect the brain cell and allows electrical impulses to travel quickly and efficiently. Dr. Ho and her team see promise for the nanotherapeutic for those with neurodegenerative diseases, including Alzheimer’s.
An Innovative Approach: Using Human Induced Neurons to Model Alzheimer’s Disease and Aging
Dr. Ho and her team designed the study to determine whether CNM-Au8 can address or reverse certain aspects of aging and of Alzheimer’s disease. The design involves another advanced technology to assess the efficacy of CNM-Au8 by investigating the effects of CNM-Au8 in aged human neurons derived from skin cell samples from Alzheimer’s patients.
This innovative study design is made possible through a partnership with Dr. Jerome Mertens of the University of Innsbruck in Tyrol, Austria. His work involves induced neurons, which are created by reprogramming skin cells to become neurons that maintain traits of aging and disease. In this case, skin cells from patients with Alzheimer’s disease are used to create neurons on which the team can evaluate the treatment effects of CNM-Au8.
Karen Ho and Michael Hotchkin, CDO of Clene
Dr. Ho expressed her enthusiasm for the collaboration, saying, “Dr. Mertens has the expertise, patient cells, and talent in his lab to execute fully on this project, while we at Clene have provided CNM-Au8, additional resources, and our expertise to the project to ensure this project’s success. We hope that with positive results from this NAM-funded study, we can rapidly advance CNM-Au8 into a Phase 2 trial for Alzheimer’s disease.”
By testing the patented nanotherapeutic on induced neurons, this project uniquely converges these new technologies and expands on existing areas of study in aging and neurodegenerative disease. Dr. Ho and her team hope this innovative study will determine if CNM-Au8 might improve the lives of the more than 6 million Americans living with Alzheimer’s.
“As we age, our ability to keep up with the body’s energetic demands becomes less efficient. The most highly energetically demanding cells, cells of the central nervous system and brain, begin to suffer the most when energy supplies dwindle,” says Dr. Ho. “We now know that CNM-Au8 works by improving the bioenergetic status of these nervous system cells. The important question we are addressing is whether this drug also works in human cells with Alzheimer’s disease.”
Supported by other funding sources, Clene also conducts research on the use of CNM-Au8 to slow the progression of amyotrophic lateral sclerosis (ALS). The latest findings suggest that patients taking CNM-Au8 treatment demonstrated improved outcomes in proof-of-concept trials. Learn more about this promising research here.
Looking Ahead: The Impact of the Healthy Longevity Program
Dr. Ho and her team are looking forward to the 2021 Healthy Longevity Global Innovator Summit on the 13th, 14th, and 22nd of September. Attendees of the summit can learn about the early-stage, award-winning innovations, hear from leaders in the field of healthy longevity, and take advantage of various networking opportunities designed to foster interdisciplinary and cross-sector collaboration. Click here to register.
“I am very much looking forward to meeting other leading research scientists in the aging and longevity field, and to broadening my current scope and understanding of the innovations that are taking place in the field,” said Dr. Ho.
She encourages other researchers interested in questions about longevity, healthy aging, and age-related disease prevention to attend the summit and apply for the Catalyst Award.
“There are two significant differences between the Catalyst Award and other funding Clene has received,” Dr. Ho explains. “The first is that the Healthy Longevity Catalyst Award application itself is streamlined into a two-page description of the background and proposed work, the second is that the funding comes as a prize with no strings attached. Both aspects honor a scientist’s ideas and time, placing in him or her the kind of freedom and trust that fosters true innovation.”