Unfortunately, I am not talking about big kids or men that behave themselves like children. Unfortunately, I am talking about something much more serious. So serious, it is lethal. Can you imagine a baby looking like an old man? Sure, if you’ve seen Brad Pitt in the movie “The curious case of Benjamin Button” you might get the idea, even when they’ve taken the idea a tinsy tiny bit too far (since symptoms usually do not become visible until after a few years after birth). Otherwise, wellcome to progeria. A genetic disease characterized by producing premature aging, and sharing characteristics of aging-related diseases like cardiovascular or bone diseases. The two best known progeric syndromes are the Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner Syndrome (WS); both of them are caused by genetic defects related either to structure of nuclear membrane (HGPS) or to DNA
integrity (WS), and even when they are relatively rare (1:4million HGPS, 1:100000 WS worldwide) the effects of this single point mutations are really severe: cardiovascular diseases such as stroke, myocardialinfarction and atherosclerosis, bilateral cataracts, type 2 diabetes mellitus, as well as osteoporosis and alopecia figure among the most typical characteristics of these early-aging syndromes. Additionally, in the case of WS there is an atypical cancer profile, which high susceptibility for neoplasms. Surprisingly though, as much as these syndromes resemble aging, there are no neurodegenerative effects and most of the affected die early from cardiovascular complications.
Why is it important to investigate, and eventually found a cure to these rare diseases? Well, firstly because of the implications it has for the patients, but secondarily because the similarities to the “normal” aging process make these diseases a very useful model for aging research. To date there is no treatment for these syndromes other than those directed towards symptom alleviation, however, great hope is placed on farnesyltransferase inhibitors (FTIs), a drug developed initially to treat cancer, since it has an effect over an oncoprotein (Ras) but that has become more extended as a progeria treatment that in animal studies was shown very effective in dealing with the disease. Trials where a combination of drugs including FTIs, statins and aminobisphosphonates (all three molecules implicated in the same molecular pathway) have shown to extend the life of progeroid patients hold promises for the future. However, caution is needed since FTIs have been shown to increase cardiovascular risk in mice. The immunosupressant rapamicin has also been shown to extend the life expectancy of these patients (probably due to activity in cellular pathways related to those active under caloric restriction and involving mTOR signaling). Looking ahead into the future, gene therapy mediated by gene editing (CRISP/Casp9) or stem cell therapy stand as the most promising avenues for curing these diseases. Since HGPS is the result of a single-point mutation it stands as an ideal target for CRISP/Casp9-mediated gene editing. Nonetheless, by now we are talking science fiction and we can only hope that more research will provide the much-needed answers and treatments for these early-onset aging syndromes.