The grant will help to support preclinical studies in patients’ nerve cells and mouse models of the disease, as well as facilitate the launch of a Phase 2 safety and effectiveness study of CNM-Au8 in Parkinson’s patients. Clene plans to initiate this clinical trial before the year’s close.
“It is an honor to have the support of MJFF as we seek to develop CNM-Au8 as a novel treatment option for Parkinson’s disease,” Rob Etherington, president and CEO of Clene, said in a press release.
The loss of dopaminergic neurons in the substantia nigra, a region of the brain that regulates muscle movement and coordination, is one of the underlying causes of Parkinson’s disease. To work as intended, these nerve cells require large amounts of energy, which is provided by mitochondria, the cell’s powerhouses.
CNM-Au8, developed by Clene Nanomedicine, is a suspension of nanocrystalline gold designed to increase the production of energy. Specifically, CNM-Au8 boosts the conversion of one molecule to another — nicotinamide adenine dinucleotide (NADH) to its oxidized form (NAD+) — leading to a greater production of ATP, the energy currency of cells.
The investigative oral treatment also has antioxidant properties that may help to protect cells against oxidative stress and lessen the accumulation of misfolded proteins, like alpha-synuclein. This abnormal protein can amass at levels toxic to nerve cells. (Oxidative stress is the accumulation of potentially harmful reactive oxygen species, also called free radicals, which can damage cells.)
Following promising preclinical data, researchers will investigate how CNM-Au8 affects survival and energetic production of dopaminergic neurons collected from patients. The lab tests will be performed in the presence of toxins known to play a role in Parkinson’s disease.
Additional research will assess the effects of CNM-Au8 on motor coordination and nerve cell survival in an animal model, data that is key to moving the therapy further into clinical development.
Work in patients’ dopaminergic neurons will be conducted in collaboration with Michela Deleidi, MD, PhD, with the German Center for Neurodegenerative Diseases (DZNE). The animal studies will be performed by James Koprich, PhD, chief scientific officer of Atuka, a research and consultancy company that helps in developing candidate therapies for Parkinson’s. All studies will be co-led by Karen Ho, head of translational medicine at Clene.
“CNM-Au8 is a promising potential treatment for PD [Parkinson’s disease] due to its nanocatalytic activity and ability to increase intracellular NAD+, decrease oxidative stress and activate genetic pathways that decrease misfolded protein accumulation in the context of neurodegenerative disease,” Deleidi said.
“I look forward to working with Clene to characterize CNM-Au8’s ability to improve neuronal survival through restoration of the bioenergetic pathways that are compromised in PD,” she added.
CNM-Au8 is being evaluated in an open-label pilot Phase 2 study (NCT03815916), called REPAIR-PD. The study may still be enrolling up to 30 patients, ages 30 to 80 and diagnosed within the past three years, at its one University of Texas Southwestern Medical Center site. More information is available here.
After a four-week screening period, enrolled patients will drink two ounces of CNM-Au8 daily each morning for 12 weeks. Treatment will be followed by four weeks of examinations.
The study’s main (primary) goal is to assess the therapy’s impact on oxidative stress in the central nervous system (CNS, the brain and spinal cord), measured by the ratio of NAD+/NADH using magnetic resonance spectroscopy. Additional (secondary) goals include evaluations of CNM-Au8 on energy production, and nerve cell metabolism.
Interim data on six treated patients showed CNM-Au8 boosted energy production in the CNS, with increases in total NAD and ATP levels, and the NAD+/NADH ratio. These results support the potential of CNM-Au8 to aid survival of dopaminergic neurons and slow disease progression.
Top-line data from this pilot trial are expected in the second half of this year.
“Interim target engagement data indicate that CNM-Au8 has a homeostatic effect on brain energetics in patients with PD that may allow it to ultimately slow or halt PD progression. We look forward to working with MJFF to build on these compelling data and accelerate the development of CNM-Au8 in PD,” said Etherington.
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