This blog post is not an argument for reductionism. Instead, it is an argument for speeding up treatments that work in the case of a complex disease like aging. While demand for such treatments exists, anti-aging clinical trials are extremely rare. Elderly patients are the most complex ones of all – it is what intellectually drew me to geriatrics as my medical specialty, but this complexity is also a nightmare in a clinical trial since you can’t really prove anything.
Like all aging species, humans get worse at dealing with stress as time goes by.
When dealing with stress, humans differ not only by age but also by kind. Being one of the few people who can’t deal with a certain protein is an unfortunate event but in the grand scheme of things, tackling such rare diseases can speed up anti-aging drug development. Many rare diseases are genetic and they mostly affect children. Not only that diagnosing a rare disease takes a lot of time and resources – which may be lacking in many places, even in developed countries – but for many of these, there is no treatment at all.
On the other hand, developing a drug for such a disease is faster and cheaper. These patients are younger so additional age-related pathology can be excluded. Huge clinical trials are not needed because there aren’t that many patients suffering from that disease. Marketing approval is speedier, at least in the EU and USA. Competition is minimal, most of the time non-existent. If something works, it could always be tested in more frequent age-related diseases where the elderly are very likely to have additional diseases. But by tackling a rare disease first, the proof of concept will be shown and people who currently have no choice will be helped.
Here are a couple of rare disease updates that could have great potential in alleviating the suffering imposed by aging.
Neurodegeneration exists not only in nursing homes but also in a few children around the world. Friedreich’s ataxia is one of those rare neurodegenerative diseases whose only treatment is symptomatic and supportive.
I don’t know anybody with this disease but it must be terrible to see your child dwindling from such a disease. A treatment for this rare disease that caught my eye is orally-administered deuterated linoleic acid by the Retrotope company.
Unlike natural linoleic acid, an essential Omega 6 PUFA-type fatty acid, the synthetic form is resistant to lipid peroxidation and it is absorbed orally. Can you envision how this could change the aging process?
Lysosomal storage diseases are particularly damaging since the lysosomes don’t recycle wastes as they should due to an enzyme that is missing or that is in short supply.
While this group of diseases affects children, it’s basically the same process as developing age spots, albeit with different faulty enzymes.
For a couple of these rare lysosomal storage diseases, intravenous administration of the missing enzyme is possible, yet biodistribution of the enzyme is not uniform, neurological symptoms are rarely improved and an immune reaction against the enzyme can develop.
The missing enzyme could be introduced in the body through a viral vector as gene therapy but such treatments are as rare as the disease we’re talking about.
Another approach that has been recently tested is substrate prevention therapy. If administering the missing enzyme doesn’t work that well or at all, maybe the substrate could be blocked from forming and accumulating. Miglustat is one such treatment administered orally in patients suffering from Gaucher disease type I.
Stargardt disease is a rare disease of juvenile macular degeneration where the ABCR protein doesn’t work, leading to lipofuscin accumulation. According to this study which checked ABCR gene variants in age-related macular degeneration (AMD), I doubt that gene therapy for Stargardt disease could one day be applied in AMD too but other therapies to prevent lipofuscin accumulation or to break up those deposits may work.
Deuterated vitamin A is currently tested to see whether it could reduce toxic vitamin A metabolites. Another promising drug could be soraprazan, hypothetically breaking up accumulated deposits from the retina which would be easier to remove by the body.
In superficial tissues like the skin, selective photothermolysis could be used to destroy cells filled with lipofuscin since this procedure is already used to remove tattoos.
Aging is not the only mitochondrial disease but we could say it is the most common one. Other mitochondrial diseases are rare diseases affecting children and young adults. Mitochondrial replacement therapy or mitochondria donation started as a technique to prevent passing on mitochondrial mutations from the mother by creating a baby with 1 father and 2 mothers, one mother passing on her share of the nuclear genome and the other one passing on the mitochondrial DNA only. As far as I know, this is approved in UK only. Unfortunately, some mitochondrial diseases are caused by mutations in the nucleus, the resulting proteins being imported into mitochondria and impairing the function of these organelles.
Still, mitochondrial replacement therapy could be used not only in preventing such mutations from being transmitted to the next generation, but also to replace faulty mitochondria in patients living today.
Two such clinical trials testing its safety in Leber’s hereditary optic neuropathy are
this one and this one.
Rare diseases are not simple to diagnose or treat.
Rare diseases are not simple to diagnose or treat, but by mostly affecting children who rarely have additional pathology, developing treatments in such cases could yield extensive benefits to everyone involved.
Many pharma companies applied to have their new drugs subsidized as ‘orphan drugs’ and once approved as such, extended their indications to common diseases.
And maybe on the short term this is a misuse of public money but otherwise, treatments for rare diseases would never have become a priority and they wouldn’t have existed. Besides, if a drug is efficient in a rare disease, should it always stay in that niche? Off-label use of any drug can prove life-saving so let’s not put the horse before the cart.
Anca Ioviţă is the author of Eat Less Live Longer: Your Practical Guide to Calorie Restriction with Optimal Nutrition ,The Aging Gap Between Species and What Is Your Legacy? 101Ways on Getting Started to Create and Build One available on Amazon and several other places. If you enjoyed this article, don’t forget to sign up to receive updates on longevity news and novel book projects!
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