Tech news: Soon you will be able to stay young forever By Louis Fourie Jul 19 – IOL

Louis Fourie

ALTHOUGH the pharmaceutical industry is constantly evolving and new therapeutic approaches are being developed, one aspect has not changed: the use of small, synthetic molecules, which still account for 90 percent of the therapeutics on the pharmaceutical market. Some of the top-selling drugs are small-molecule drugs.

Small-molecule drugs

A small-molecule drug is an organic compound of low molecular weight (less than 900 Daltons or 1,49449-21 grams) and the size of about one nanometre capable of modulating biochemical processes to diagnose, treat or prevent diseases.

Because of their low molecular weight, small-molecule drugs have some definite advantages as therapeutics, because most can be administered orally and can pass through cell membranes to reach intracellular targets. Once inside the cells, they can be designed to engage biological targets, such as proteins, by various modes of action. Their distribution can also be customised, for example, to allow for systemic exposure or to destroy cancer cells. Therefore, many targeted therapies today are small-molecule drugs made from synthetic chemical reactions. However, they are also used in pesticides and in many other roles.

One well-known small-molecule drug is aspirin, which has been with us since 1899. Currently, the world consumes about 40000 tons of aspirin every year for a range of indications, such as cardiovascular health, Alzheimers disease, cancer treatment, pulmonary diseases, and everyday aches and pains. Another classic example is the drug penicillin, which successfully reduced the death rate caused by bacterial-related pneumonia to less than 1 percent during World War II.

Although small-molecule drugs have dominated the pharmaceutical industry since the beginning of modern medicine, it seems as though major developments are now happening in biologics, despite their excessive cost. RNA interference and CRISPR-Cas9, for example, are exciting new gene-editing tools.

But it is not the end of small-molecule medicine. Recent discoveries of small molecules that can modulate protein-protein interactions have created renewed interest in and utilities for small-molecule drugs for many diseases.Furthermore, the ability to design small molecules that can interact with and modulate RNA could create new opportunities for targeting challenging disease pathways.

An anti-ageing drug

Although with us for many years, the rapid advancement of biopharmaceutical research and technology opens up many opportunities for inventive and ingenious approaches to developing small-molecule drugs. We have therefore in recent years seen that significant advancements in structure-based design and imaging, together with automation, artificial intelligence and machine learning, have become important enablers to expedite research and enhance the success rate of small-molecule-led optimisation.

One of these innovative small-molecule drugs that could delay ageing is being tested by the US Militarys Special Operations Command (Socom), the organisation that controls the USs Special Operations forces. The anti-ageing pill comprises a human performance small molecule in the form of a nutraceutical with the aim of improving performance characteristics such as endurance and faster recovery from injuries, which typically declines with age.

Socom is working with the private biotech laboratory Metro International Biotech (MetroBiotech) on the development of an anti-ageing pill based on a human performance small molecule.

MetroBiotech is an offshoot of David Sinclairs Harvard University Medical School laboratory. The first-in-class small molecule on which they are working is Nicotinamide Mononucleotide (NMN), which MetroBiotech describes on their website as an enhancer that leverages the nicotinamide adenine dinucleotide (NAD+) cycle that is critically important to the function of all living cells and also to treat rare mitochondrial diseases and other medical conditions. These rare mitochondrial diseases often have serious effects on skeletal and cardiac muscle, as well as the central nervous system.

Increased NAD+ levels have been shown to induce mitochondrial biogenesis and enhance natural pathways (for example, sirtuins a family of dormant proteins found in all living beings) that are key to improving mitochondrial health. Mitochondria are cell parts (organelles) that produce energy for the cell in the form of a chemical called adenosine triphosphate (ATP). Cells need ATP to function properly, and NAD+ is a cofactor required for the enzymatic processes that generate energy within the cell through the continuous production of ATP inside the mitochondria.

Research has demonstrated the broad therapeutic potential of increasing NAD+ levels to preserve health and normal metabolism. It increases mitochondrial health and longevity, rejuvenates stem cells and provides neuroprotection. In general, it improves the health of most organs such as the brain (neurodegeneration), heart (inflammation, cardio protection), liver fatty acid oxidation, gluconeogenesis or regeneration), pancreas (insulin secretion), and skeletal muscles (insulin sensitivity, fatty acid oxidation) and white adipose tissue or white fat (lipogenesis).

Ageing and certain diseases, such as mitochondrial dysfunction, inflammation and other associated diseases, cause a decline in the NAD+ levels in humans, with serious consequences with regard to energy, performance and endurance. Treating people with NAD+ could thus slow the degenerative effects of ageing, prevent the onset of injury and thus allow people, according to MetroBiotech, to lead longer and healthier lives.

Several studies have been published in respected journals indicating how supplementation with a NAD precursor delays motor neuron degeneration, decreases markers of neuroinflammation in the spinal cord, improves blood flow, heart pathology, and musculoskeletal endurance, slows Alzheimers, improves energy metabolism, insulin sensitivity and plasma lipid profile, reverses retinal degeneration, mitochondrial biogenesis in skeletal muscle, and prevents noise-induced hearing loss and spiral ganglion neuron degeneration after noise exposure.

Since the small-molecule drug is a nutraceutical, a dietary supplement or food containing health-giving additive with medicinal benefit, it is not regulated by the US Food and Drug Administration and is therefore exempt from the rigorous standards regulating prescription drugs. It seems that MetroBiotech is following the nutraceutical route and not that of a prescription drug, because ageing is not yet itself a diagnosable disease to be treated by a prescription. Still, Socom have finished pre-clinical safety and dosing studies, and will soon start performance testing of the anti-ageing pill in clinical trials.

The thinking behind the anti-ageing pill is to address the cause of mitochondrial diseases and cure them all at once instead of the current repetitious and often futile one-by-one approach. According to MetroBiotech, its technology also supports key organ functions and could slow neurodegeneration, decrease inflammation in the body, increase cardio protection and improve sleep. NAD+ can apparently also reduce the functional effects of ageing on the human body, such as speed and reaction time.

A pipedream or a breakthrough?

For as long as humans have existed, they have been on a quest for a magic substance that would extend life or even bestow immortality. Over the years, the medieval alchemists and many others pursued the elixir of life. The slowing or prevention of ageing has therefore long been the Holy Grail of medicine, but has largely evaded us until now, except for a few studies in their infancy, such as Israeli oxygen therapy to increase telomere length and decrease the number of senescent cells (geriatric cells that can no longer divide).

The anti-ageing pill of MetroBiotech that slows down ageing and keeps you young may therefore sound like a sci-fi story. We will thus have to wait for the clinical trials to prove that NAD+ can indeed do what MetroBiotech is claiming it can do. However, the US military has spent serious money on this nutraceutical about R41 million since 2018. It must thus indeed be a promising drug that could become a game-changer in slowing the effects of ageing and preventing the onset of injuries. Despite being a controversial figure and often criticised, Sinclair may indeed be on the verge of a public health breakthrough that we have never seen before.

See you at our 150-year party!

Professor Louis CH Fourie is a technology strategist.

*The views expressed here are not necessarily those of IOL or of title sites.

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Tech news: Soon you will be able to stay young forever By Louis Fourie Jul 19 - IOL