Determining the Restorative Potential of GV-58 to Prevent Age-Related Muscle Weakness

To keep up with the world’s rapidly aging population, the NAM launched the Healthy Longevity Global Competition, a multi-stage global competition designed to seek out bold, innovative, and breakthrough ideas that challenge the way we think about aging. The Catalyst Award, the first stage of the competition, rewards exciting opportunities that display prospective improvement in the mental, physical, and social well-being of individuals as they age. Stephen Meriney is one of NAM’s 46 U.S.-based Catalyst Awardees. We hear from Stephen, a professor at the University of Pittsburgh, who speaks to the Catalyst award-winning project seeking to combat the number of fatal and injury-producing falls in older individuals by utilizing a novel compound treatment.

Can you share a little bit about yourself and your team? How did you come to work together? What advantages does your interdisciplinary team bring?

Our team includes myself, two research assistant professors (Yomna Badawi and Tyler Tarr), and a graduate student (Nick Li). I have been studying the neuromuscular junction in healthy and diseased state for over 30 years and have a research program focused around motor nerve terminal structure, function, and the development of new therapeutic approaches to strengthen the neuromuscular junction. I recruited this team to join my lab and Yomna and Nick began the research focused on aging at the neuromuscular junction. Yomna joins the laboratory from the University of Kansas Medical Center after 6 years of research experience studying the neuromuscular junction using aging mouse models. Nick is a fourth year graduate student who choose my laboratory for his PhD research and has chosen to study aged neuromuscular synapses.   

Please provide a brief description of your innovative idea/project and explain why it is particularly innovative, bold, and/or novel?

We hypothesize that exposure of aging synapses to a novel voltage-gated calcium channel gating modifier (GV-58), which increases calcium flux during normal action potential activity, will lead to a recovery of neuromuscular transmission and muscle strength.  Addressing age-induced frailty by targeting the presynaptic function of the NMJ is novel, as many previous studies have targeted muscle. The novel small molecule Ca2+ channel modulator (GV-58) that we have developed has the potential to transform the treatment of neuromuscular weakness and applying this approach to age-induced dynapenia is innovative.  

What inspired you to develop your project? Was your original goal improving health for people as they age or did that became apparent later on in the process?

We were initially focused on developing a novel calcium channel gating modifier drug to address neurological diseases (such as Lambert-Eaton myasthenic syndrome, Spinal muscular atrophy, and Amyotrophic lateral sclerosis), but we also were studying aging at the neuromuscular synapses and realized that this approach might have great potential for this indication as well.

How might your innovative idea/project lead to a future breakthrough in the field of healthy longevity?

Our candidate therapeutic has the potential to improve the quality of life of aged individuals that was previously unobtainable using traditional methods targeting frailty, which had focused on muscle wasting (sarcopenia) or promoted resistance exercise training (which is not easy for the elderly to maintain). 

NAM is Seeking Applicants for its 2022 U.S.-Based Healthy Longevity Catalyst Awards!
Applications will be accepted from January 17, 2022, through February 28, 2022 at 11:59 pm EST. Applicants from all fields, backgrounds, industries, and specialties are encouraged to complete the unique and simple 2-page application to earn $50,000 USD in seed funding for their innovative projects.

How do you see your project advancing in the future?

We are working to collect the data that will allow us to advance an investigational new drug application to the FDA over the next five years so that we can evaluate the safety and efficacy of our new candidate therapeutic in humans. The Catalyst Award provides the critical support necessary to collect these preclinical data. This support will directly be applied to the evaluation of the effectiveness of our therapeutic candidate. Without this support, such experiments could not be conducted.

What motivated you to apply to the Healthy Longevity Catalyst Awards? What advice would you have to other prospective applicants?

We were drawn to the Health Longevity Catalyst Awards because of the focus on new innovative ideas to address issues in aging.  We felt that our research program fit this goal well. This award has given us the much-needed support we need to move our ideas forward. It has also allowed us to focus on health longevity as a priority in our laboratory.

Stephen Meriney is a professor of neuroscience and psychiatry at the University of Pittsburgh and the chair of the department of neuroscience. He leads the Meriney Laboratory, which focuses on synaptic function, plasticity, and neuromuscular disease and dysfunction.

Researchers with project proposals can apply here in January 2022 when the Catalyst Award Application opens. To learn more about the NAM’s Catalyst Awardees, check out these stories. For more information about the global Healthy Longevity Global Competition, click here. We appreciate your support in advancing innovative solutions to promote health throughout the human lifespan. Email for questions about the award.

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