Scambi di organi e terapia genica preventiva di massa per prolungare la durata della vita / Organ Swaps and Mass Preventative Gene Therapy to Extend Lifespan

Scambi di organi e terapia genica preventiva di massa per prolungare la durata della vita / Organ Swaps and Mass Preventative Gene Therapy to Extend Lifespan

Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa

Boyang Wang, fondatore del fondo di venture capital Immortal Dragons, investe in progetti ambiziosi per prolungare la vita e sfidare la filosofia fondamentale della medicina.

La scienza dell'invecchiamento e della durata della vita, spesso chiamata geroscienza, è circondata da clamore e scetticismo. La copertura mediatica tradizionale tende a concentrarsi su affermazioni poco rigorose su integratori che prolungano la durata della vita nei topi o su idee così estreme da sembrare eticamente e tecnicamente fuori portata. Solo nell'ultimo anno, l'idea dello scambio di organi e dei trapianti di testa è passata dall'essere una trama di fantasia ad un argomento di discussione tra leader mondiali ripresi da un microfono acceso.

L'espressione "rendere la fantascienza realtà" si sta diffondendo nel mondo della medicina di precisione, e per una buona ragione: abbiamo assistito ad alcuni incredibili progressi terapeutici e diagnostici che forse non sarebbero stati nemmeno concepibili un secolo fa. Sarà il prolungamento della durata della vita?

L'ospite di oggi ne è convinto. Boyang Wang è il fondatore di Immortal Dragons, una società di investimenti sulla longevità con sede a Singapore, un fondo dedicato a supportare le aziende che lavorano per prolungare la durata della vita e la salute. Questi investimenti spaziano dalla stampa di organi alle terapie geniche preventive ed ai vaccini per pazienti ad alto rischio affetti da malattie complesse e che consumano risorse. Alcune di queste idee non sono più ai margini dell'immaginazione; sollevano invece interrogativi più profondi su come definiamo la medicina, la prevenzione e l'invecchiamento stesso.

Laureato in informatica, Wang ha trovato il successo come ingegnere ed imprenditore nel mondo della tecnologia. Dopo aver costruito un'attività solida, ha deciso di concentrare tempo e risorse su ciò che più contava per lui: la longevità umana. Immortal Dragons gestisce ora il suo primo fondo, un veicolo da 40 milioni di dollari che ha sostenuto circa una dozzina di aziende specializzate nella longevità sottofinanziate, scommettendo audacemente su quale potrebbe essere il futuro della medicina.

Se guardiamo al futuro, lo xenotrapianto è ovviamente una possibilità, e rientra ancora tra le nostre patologie sostitutive. Poi ci saranno delle decisioni da prendere. Se, diciamo, abbiamo un paziente con un rene che funziona a malapena, la decisione sarà tra sottoporsi ad uno xenotrapianto, aspettare un donatore o sottoporsi alla dialisi. Lo xenotrapianto è ancora un intervento chirurgico di grandi dimensioni. Ci sono tutti i rischi associati, e quando arriveremo a un punto in cui sarà ragionevole prendere in considerazione un intervento di xenotrapianto per una lieve disfunzione renale od addirittura per migliorare la salute o la longevità? Ciò potrebbe richiedere, ad esempio, una robotica in grado di eseguire questo intervento con elevata precisione. Anche queste sono interessanti tecnologie periferiche che possono essere sviluppate.

 

IPM: Hai un'opinione sulla regolamentazione degli Stati Uniti o su alcune aree del mondo e su cose che un paese come gli Stati Uniti, fortemente regolamentato, potrebbe imparare da aree più deregolamentate? 

Wang: È un argomento che va sostenuto: avere il diritto di provare è un diritto umano, dando così una possibilità di vita. Di recente, è stata approvata una legge del New Hampshire, l'HB-701, che riconosce ai malati terminali il diritto di provare, in base alla quale è sufficiente la prescrizione o la raccomandazione di un medico ed alla condizione di essere malati terminali. Credo che ci siano alcuni dettagli nella legge che affermano che è necessario aver esaurito altre possibilità.

Con questo, probabilmente Messico e Tijuana non saranno più destinazioni popolari, né lo saranno Roatan, in Honduras, perché negli Stati Uniti è possibile farlo. Questo è uno dei vantaggi di avere un potere legislativo federale rispetto ai diritti statali, in modo da poter sperimentare e vedere cosa succede. Personalmente, sono ottimista su questa proposta di legge e prevedo che alcuni medici apriranno la loro attività grazie ad essa. 

 

IPM: C'è un'ultima cosa che vorresti che sapessimo prima di uscire?

Wang: Gli studi clinici su questo argomento saranno particolarmente difficili. Ad esempio, come si misura la longevità? Se dico che questo intervento è positivo per la longevità, come possiamo misurarlo? E ci sono tonnellate di orologi biologici. E a dire il vero, molti sono scadenti o non così ben consolidati, per usare un eufemismo. 

Vorrei invitare altre persone che potrebbero essere interessate alla medicina preventiva a riflettere su quanto sia importante per tutti, in modo che alla fine possa essere utile a me ed a tutti.

ENGLISH

Boyang Wang, founder of venture fund Immortal Dragons, invests in moonshot projects to extend life and challenge medicine's core philosophy

The science of aging and lifespan—often called geroscience—is surrounded by hype and skepticism. Mainstream coverage tends to focus on non-rigorous claims about supplements that extend lifespan in mice or on ideas so extreme they feel ethically and technically out of reach. Just in the past year, the idea of organ swapping and head transplants went from a fiction plotline to a topic being discussed by world leaders caught on a hot mic.

Phrasing around “making science fiction real” is spreading through the precision medicine world, and for good reason—we’ve seen some incredible therapeutic and diagnostic advances that may not even have been conceivable a century ago. Is lifespan extension next?

Today’s guest believes it is. Boyang Wang is the founder of Singapore-based longevity investment firm Immortal Dragons, a fund dedicated to supporting companies working to extend lifespan and healthspan. These investments range from organ printing to preventative gene therapies and vaccines for high-risk patients with complex, resource-draining diseases. Some of these ideas no longer live at the edge of imagination; instead, they raise deeper questions about how we define medicine, prevention, and aging itself.

Trained as a computer scientist, Wang found success as an engineer and entrepreneur in the tech world. After building a stable business, he decided to focus his time and resources on what mattered most to him: human longevity. Immortal Dragons is now managing its first fund, a $40 million vehicle that has backed roughly a dozen underfunded longevity companies—placing bold bets on what the future of medicine might become.

IPM: As an “outsider” who wasn’t trained as a clinician and hadn’t worked in the biotechnology and pharmaceutical industry, what medical questions fascinate you and have inspired the work you’re funding today? 

Wang: I have been a patient. I’ve never been a doctor, but I’ve had interesting medical conditions since I was young. So I witnessed firsthand the marvels and the limitations of modern medicine. I’m very grateful, but I know we’re still early; we’re still pioneers.

I have a few observations or even opinions about medicine and about healthcare. For example, we have principles for doctors where we should do no harm. That’s of course sensible. If you decide, according to a diagnostic menu, that a patient is not pathological and is not considered sick, then typically doctors would not do any intervention (and do no harm). But is that really rational? Is that the best way to do it? You can start some intervention that has minimal risks or side effects or adverse events but will give that patient 20 more healthy years down the road, that would be great. But currently nobody is doing it.

This is not even preventive medicine. Even more aggressive preventive medicine advocates will not go for such intervention. I want to invite real doctors and healthcare professionals to think about this.

If you look at vaccines, we give vaccines to infants. For some critical vaccines, it’s compulsory. It’s like universal. We give it to every kid that’s ever born nowadays, and there are adverse events. It’s not zero risk. There is some risk, and we rule that the benefits are always the risks. But we are not doing this for adults. We’re not doing this for some of the upcoming interventions.

 

IPM: What are some examples of aggressive preventative medicine ideas?

Wang: Cardiovascular disease is still the number one killer. Some ethnicities and groups of people are especially vulnerable to cardiovascular disease and we know that LDL is a main risk factor. According to the manual, you have several standards, but according to studies, if you can lower LDL further, it’s usually beneficial. There were suggestions. I don’t know how serious it is to add statin to tap water so that everybody can have it. But I guess no, but that’s one of the examples I have. Statins are cheap and readily available. We know the risks very well. And then probably there’s a possibility to give at least a proportion of the population statins early on and maybe that will do them good.

On top of statins, PCSK9 inhibitors are a class of drugs that were developed in the past decade. It has demonstrated a very good safety profile. Again, it lowers LDL and it’s a separate pathway such that they work; they can work hand in hand with statins or stand alone. And even fewer adverse events, according to the data we have so far. How about these? Of course, PCSK9 inhibitors are still relatively expensive, and that stops them from becoming a more widespread intervention. I’m an outsider. I’m not a healthcare professional. I’m not promoting these as medical advice. For healthcare professionals, these are interesting ideas but I don’t know how people would quite feel about it.

When it comes to the cost of PCSK9 inhibitors, if we take Leqvio (inclisiran), which is like the latest form, you get one shot every six months. That’s how it is currently administered, and one shot is probably $2,000. That sounds like a lot, but if you consider all the medical bills that can potentially be saved, if you think about the additional healthy years, and how much it’s worth to the individual and to the society as a whole in terms of productivity, probably it’s worthwhile. We can leave it to the insurance companies to work out the math, but it’s probably worth it.  

 

IPM: You are a gene therapy patient. Not many people have received gene therapy. What are your thoughts on gene therapy in lifespan extension?

Wang: Gene therapy is one of the investment theses of our fund. We are very bullish on gene therapy. There are gene therapies specifically dedicated to genetic defects, but potentially there can be gene therapies for other purposes, even anti-aging longevity. If they can have any level of success, that will be huge. I’m talking about interventions that are, for example, for hair growth and muscle atrophy. These are real examples.

Two years ago, I was still relatively new in the field, formulating the fund and investing as an angel investor. That’s when I came across the first wave of gene therapy companies for the masses, and they are controversial, to say the least. I’m talking about companies like BioViva and Minicircle. I went to this place, Roatan, Honduras, where I received the gene therapy. A group of people struck a deal with the Honduran government, which has these special economic zones where they can have more lenient or more flexible regulations about medical interventions, but also about other things, like taxes or other laws. So they can operate in Rutan and they can give a more lenient right to try for such therapies.

Most of the experts I consulted said, “[follistatin gene therapy] is not going to do anything at all. You’ll just lose your money.” I was cautious about the risks, asking about dosage and delivery vector—will there be risks and what are they? The therapy is a polyethyleneimine (PEI) polymer. It’s a very low dosage. Experts said, “You are probably going to be fine, and you’ll be wasting your money—don’t do it.” So, the risk is pretty much accounted for.

There were about 200 to 300 who had received the therapy before me. I was like the 300th test subject. This will be a fun experience. This will be a great opportunity to experience it firsthand. I really support the first wave of companies that are bold enough to produce a gene therapy for potentially the masses. That was the reasoning behind receiving that gene therapy of follistatin from Minicircle. As the expert suggested, I don’t see anything from my blood test. I don’t feel anything. I feel fine.

 

IPM: What is the state of bioprinting and organ replacement strategy?

Wang: Replacement strategy as a whole is one other main investment thesis. Consider electronics. We have built very complicated electronic devices, and we, our biological body, are a super complex machine that we still have not yet tackled. If we see electronics, they are complex enough such that if you smash your iPhone, even the very best engineers in the world, no matter how much you spend, cannot glue back all the shards and give you a brand-new iPhone. But what can we do? We can swap the screen and the motherboard, and pretty much you have your iPhone with all the memories and previous storage but brand new and functioning correctly. There are really thousands, millions of ways for a complex machine to go wrong. You really cannot figure out and anticipate all of the ways it could go wrong, but there is pretty much just one way for it to function correctly, other than some accidental cases. So we draw that analogy to human. This probably is a great idea to replace, well, tissues, organs or organ systems rather than trying to fix them.

Now, when it comes to replacement strategy, there are more aggressive ideas and companies working on it, but there are also things that are already pretty close to a clinical application. I’ll take one company in our portfolio as an example. Frontier Bio is one of the companies that we were able to support. They are in the 3D biofabrication space. Of course, 3D biofabrication or 3D bioprinting, is the idea where we want to create components or pumps for you in vitro, outside of your body, so the risk is minimized. What can they print?

We cannot print a whole organ yet, but we are already able to print brain tissues, and that’s already very useful for R&D purposes. For example, when Neuralink develops a brain-computer interface, the company needs to conduct very extensive testing. To do that, they create small brain tissue in a vat. It’s a primitive version of a brain in a vat; it’s brain tissue in a vat without vascularization. And then they will have their probes, their chips, connected to the brain tissue, and then they do all that.

A more accessible idea is that they harvest your somatic cells, they produce iPSCs, and then they will print or spray your stem cells onto a scaffold and with the right environmental and chemical cues, the stem cells would derive into endothelial cells, eventually into a blood vessel and that blood vessel can come in handy when it comes to a surgery like cardiovascular bypass or a graft. The current state of the art is to take a segment of blood vessel from your thigh, for example, but that’s traumatic and sometimes it’s not applicable for some patients. FDA has already approved the very first case of 3D-printed blood vessels for use in some acute surgical situations.

From blood vessels for surgery to brain tissue or liver tissue for R&D purposes, eventually one day we want to reach a point where we can biofabricate organs. But even before that, this will be tremendously useful for some organs that are more homogeneous, like the liver. You don’t need an entire liver to help a patient. You can just have some healthy liver tissue and it can already be implanted and function in your body. So that’s the idea of Frontier Bio, and that’s what we mean by replacement strategy. 

If we take a look at the future, there is, of course, xenotransplantation as a possibility, and that still fits within our replacement diseases. Then there will be decisions to be made. If, let’s say, we have a patient who has a kidney that is barely working, the decision will be getting a xenotransplant versus waiting for a donor versus dialysis. Xenotransplantation is still a huge surgery. There are all the risks associated with it, and when will we reach a point where it’s even reasonable to consider a xenotransplant surgery for minor kidney malfunction or even eventually for health-boosting or longevity purposes? That might require, for example, robotics that can do this surgery with high precision. Those are also interesting peripheral technologies that can be developed.

 

IPM: Do you have a take on the U.S.’s regulation or certain kinds of areas of the world and things that maybe a country like the U.S. that is very highly regulated could learn from more deregulated areas? 

Wang: It is an argument to be made that it is a human right to have a right to try, thereby giving them a shot at life. Recently, there was the passing of a recent New Hampshire bill, HB-701, which gives terminally ill patients a right to try, where you just need the prescription or recommendation from one doctor and you need to be terminally ill. I think there are some specifics in the bill saying that you must have exhausted other interventions.

With that, probably Mexico and Tijuana will no longer be popular destinations, nor will Roatan, Honduras, because people can do it in the United States. That’s one of the advantages of having a federal-level legislature versus state rights, so that we can experiment and see what happens. Personally, I’m bullish on this bill, and I’m just anticipating some doctors will establish their practice under that bill. 

 

IPM: Is there any last thing you’d like for us to know before we go out?

Wang: Clinical trials for this topic will be particularly hard. Like, how do you measure longevity? If I say this intervention is good for longevity, how can we measure that? And there are tons of biological clocks. And to be honest, many are crappy or not that well established, to say the least. 

I want to invite others who might be interested in preventive medicine to think about how it’s relevant to everybody so eventually it benefits me and everybody.

Da:

https://www.insideprecisionmedicine.com/topics/translational-research/organ-swaps-and-mass-preventative-gene-therapy-to-extend-lifespan/?_gl=1*col84f*_up*MQ..*_ga*MTczNjU2MzE4Ny4xNzY3ODI1MTg1*_ga_Y3KXM38M5E*czE3Njc4MjUxODUkbzEkZzAkdDE3Njc4MjUxODUkajYwJGwwJGgxNTkxNzI0MTAy