The US military says there are just a few months to start clinical trials of a pill designed to block or reduce many degenerative effects of aging – an oral treatment that a leading researcher in the field says is worth better than nothing while wondering how effective it will be.

The United States Special Operations Command (SOCOM) – which develops and employs special operations forces around the world to advance United States policies and objectives – has “completed preclinical safety and security studies. assay in anticipation of follow-up performance tests ”of a first nicotinamide adenine dinucleotide. , oxidized activator (NAD +), a small molecule drug developed by Metro International Biotech (MetroBiotech), Navy Cmdr. SOCOM spokesperson Timothy A. Hawkins said GEN.

SOCOM and MetroBiotech are expected to begin clinical trials in the 2022 federal fiscal year, which begins October 1.

“If preclinical studies and clinical trials hold true, the resulting benefits include improved human performance, such as increased endurance and faster recovery from injury,” Hawkins said.

“This particular effort aims to improve the mission readiness of our forces by improving performance characteristics that generally decline with age,” said Hawkins. “These efforts are not aimed at creating physical traits that don’t already exist naturally.”

The SOCOM test is part of the ongoing studies to assess MetroBiotech’s lead candidate, said David J. Livingston, PhD, president and CSO of MetroBiotech. GEN.

“I can confirm that we and our clinical partners have completed several phase I human safety trials of a flagship molecule,” said Livingston. “Metro has also initiated exploratory Phase II studies in several areas of therapeutic application, in particular the treatment of rare diseases, diseases of aging, and in collaboration with SOCOM, studies on the effects of our compounds on muscle energy. and human performance. “

Livingston said MetroBiotech will not discuss details of its clinical trials until future posts to ClinicalTrials.gov or joint clinical data posts.

Potential to “really delay aging”

SOCOM has spent $ 2.8 million on its anti-aging efforts since its debut in 2018, Hawkins said.

Lisa R. Sanders, director of science and technology for special operations forces, acquisition, technology and logistics, told a virtual conference last month that SOCOM was able to fund its anti-aging testing through the Other Transaction Authority (OTA) and Middle Level Acquisition Authority funds, established in 2015 to enable rapid acquisitions designed to deliver capability within 2-5 years.

“This small molecule has the potential, if successful, to really delay aging. [and] really preventing the onset of injury, which is an incredible game changer, ”said Sanders, speaking to“ Assisting the Modern Warfighter, ”a featured session held as part of the Defense One Defense Technology Summit, from June 21 to 25.

“We have stayed out of long-term genetic engineering – which makes people very, very uncomfortable – but there is a huge commercial market for things that can prevent injury, that can slow aging, that can improve sleep, ”Sanders added.

This market is expected to grow 55% over the next five years, according to market research published in January by 360 Market Updates, from $ 84.6 billion this year to $ 130.87 billion by 2026, or a compound annual growth rate of 7.5%.

“Better than nothing, but …”

Can MetroBiotech’s treatment be the one that can tap into this potentially lucrative anti-aging market?

“It’s better than nothing, but not much better,” warned Aubrey DNJ de Gray, PhD, a biomedical gerontologist who is CSO and co-founder of the SENS Research Foundation. De Gray is also editor-in-chief of Rejuvenation research, a peer-reviewed journal published by GEN publisher Mary Ann Liebert, Inc., editors.

Based in Mountain View, California, the SENS Research Foundation aims to prevent and reverse age-related health problems by applying the principles of regenerative medicine to repair the damage of aging to where it occurs. The foundation focuses on rejuvenating biotechnologies designed to restore normal functioning of body cells and essential biomolecules, restoring the health of aging tissues and restoring youthful vigor to the human body.

According to de Gray, SENS’s anti-aging approach contrasts with that of MetroBiotech, which he described as reflecting a consensus point of view within gerontology towards a simple reduction in the rate of cellular damage due to aging.

“Unfortunately, the field of gerontology took it another way, which was to try, in effect, to clean up the metabolism, slow down the rate at which the metabolism generates damage and thus delay the age at which damage reaches that pathogenic threshold. This has essentially failed, “said de Gray.” The pill that MetroBiotech is reviewing is likely to fail, for this reason. “

This is not the case, insists MetroBiotech.

“Our company’s strategy is to design small molecule therapies that take advantage of our scientists’ detailed understanding of the biochemistry and genetics of human aging pathways and the stress response,” said Livingston. “Based on the findings in these exciting areas of biology, Metro has created a library of novel activators of NAD as therapeutics for the treatment of human diseases and the preservation of muscle and cognitive performance. “

Building the NAD + portfolio

MetroBiotech, a private company based in Worcester, MA, States on its website it has established “the most comprehensive portfolio of exclusive NAD + precursors in the world”. The company believes that increasing NAD + for maintaining health and normal metabolism has broad pharmaceutical potential, as NAD + levels have been shown to decrease with age. Reduced levels of NAD + are linked with aging and with many diseases, including mitochondrial dysfunction, inflammation, and various related diseases.

NAD + plays a key role in the functioning of all living cells, as a required cofactor for enzymatic processes that generate energy in the cell through the adenosine triphosphate (ATP) cycle, both in traditional oxidoreductase reactions and as a signaling molecule for reactions catalyzed by sirtuins, which regulate cell health, and poly-ADP ribose polymerases (PARPS), proteins that help cells repair themselves.

The lead candidate in MetroBiotech’s pipeline, MIB-626, is one of more than 100 new NAD + activators that the company claims to have designed, synthesized and screened for optimal therapeutic properties. MetroBiotech says its efforts have resulted in “robust” preclinical data that supports the broad therapeutic potential of NAD + modulation.

More recently, in a study published last year in the review Experimental neurology, researchers from the Medical University of South Carolina and the Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland are studying two approaches to increase the NAD⁺ availability in mouse models of amyotrophic lateral sclerosis (ALS): Ablation of a NAD⁺– consuming enzyme (CD38), and supplementation with bioavailable NAD⁺ precursor, nicotinamide riboside or NR.

While the ablation approach showed no effect on the survival of mouse models, the addition of NR delayed motor neuron degeneration, decreased markers of neuroinflammation in the spinal cord, appeared to alter metabolism. muscle and slightly increased the survival of hybrid superoxide dismutase 1 G93A (hSOD1^G93A) mouse model of ALS.

“The results indicate that the approach used to improve the NAD⁺ levels critically defines the biological outcome in models of SLA, suggesting that the increase in NAD⁺ levels with the use of bioavailable precursors would be the preferred treatment strategy for ALS, ”concluded the researchers in the study, whose corresponding author Marcelo R. Vargas, PhD, is now at the University of Wisconsin-Madison.

“Get something that works”

While acknowledging that an oral treatment to reverse aging would be much easier for patients than a surgical approach, de Gray of SENS added; “The way I see it is, first of all, to get something that works, even though it’s really unpleasant in terms of surgery, then you can refine it and make it injectable and maybe even oral. . “

He cited the growing interest of researchers in an anti-aging application for an already marketed drug that has long been used by patients. Treatment of type 2 diabetes Metformin should be the subject of the proposed Targeting Aging With Metformin (TAME) trial. TAME, to be managed by the American Federation for Aging Research, will be a series of six-year national clinical trials at 14 leading research institutes in the United States, designed to involve more than 3,000 people aged 65 to 79.

Another potential anti-aging treatment already in clinical study is rapamycin, a natural antifungal antibiotic that has shown anti-tumor and immunosuppressive activity. The University of California, Los Angeles, partnered with AgelessRx last year to launch the Participatory Phase II (of) aging trial (with) rapamycin (for) the longevity study ( PEARL) (NCT04488601), designed to test rapamycin in approximately 1,000 elderly people.

“The researchers aim to establish a long-term safety profile, to determine the long-term efficacy of rapamycin in reducing clinical measures of aging and the biochemical and physiological parameters associated with declining health and aging in patients. healthy elderly people, ”according to the clinical trials of the trial. government page.

MetroBiotech has disclosed a clinical trial for its lead candidate NAD + MIB-626 on ClinicalTrials.gov. The phase II trial (NCT04817111) does not involve SOCOM, but rather is designed to assess MIB-626 in up to 10 adults with Friedreich’s ataxia (FA) without overt heart failure and with a left ventricular ejection fraction ≥ 40%.

“A key secondary goal is to test the effects of MIB-626 on cardiac bioenergetics and skeletal muscle,” according to MetroBiotech.

The estimated primary completion date for the trial is April 10, 2022.