[HN Gopher] Longer proteins for longer lifespan?
       ___________________________________________________________________
        
       Longer proteins for longer lifespan?
        
       Author : bilsbie
       Score  : 38 points
       Date   : 2022-12-13 16:36 UTC (6 hours ago)
        
 (HTM) web link (joshmitteldorf.scienceblog.com)
 (TXT) w3m dump (joshmitteldorf.scienceblog.com)
        
       | ray__ wrote:
       | The idea that aging research is being stifled by patent law (or
       | any other mechanism) is ridiculous. Aging and neurodegenerative
       | disease already receive an exorbitant amount of funding from the
       | government (see: the NIA). The aging billionaire class is also
       | more than happy to fund aging research that works for them (see:
       | Altos Labs as the most recent example, The SENS Research
       | Foundation, and tech life sciences offshoots like Calico). The
       | argument that you "can't patent naturally occurring proteins" may
       | be technically true, but there are plenty of ways around this
       | which often improve the performance of the native proteins as
       | therapeutics (see: insulin, among many others).
       | 
       |  _" Leapfrogging ahead of these research institutes with a
       | practical demonstration has been Harold Katcher. Katcher's method
       | is proprietary."_
       | 
       | Wow, a proprietary method that outdoes decades of scientific
       | research? Haven't heard that one before. I understand that there
       | has been little progress in this space, but that's because no one
       | knows what causes aging (or if it can be halted at all). There's
       | no single smoking gun, and there is likely no single easy
       | solution. I also understand that our scientific institutions
       | aren't perfect-and that the big ship of science can sometimes
       | take a while to turn away from a tantalizing hypotheses, like the
       | amyloid hypothesis-but that doesn't mean that you should trust
       | Harold Katcher instead.
       | 
       |  _Presumably, longer proteins require more splicing, so impaired
       | RNA splicing could account for a deficit of longer proteins as we
       | age._
       | 
       | Why is this "presumably true"? Intuitively, impaired splicing
       | would produce longer proteins, because introns aren't excised as
       | effectively. Even this take is far too simplistic-there are
       | innumerate feedback and control mechanisms involved in mRNA
       | splicing. I'm sure the author has a better grasp on molecular
       | biology than this hot take suggests based on his credentials, but
       | the treatment of this topic by the author is concerning.
       | 
       | As an aside, wow, that preprint spent over three years in review,
       | and the figures and text are way different. A lot of work and
       | stress must have gone into it.
        
       | aszantu wrote:
       | NAD seems to have some rejuvenation effect. It's a refined
       | vitamin b component.
        
         | hanselot wrote:
         | If only it was cheap enough to take regularly...
        
       | macrolime wrote:
       | The mentioned E5 plasma fraction has seemingly led to a new
       | lifespan record for Sprague Dawley rats.
       | 
       | "The female lifespan study, in which E5 is being tested on
       | elderly female rats, is still ongoing because of an extraordinary
       | fact: one of the treated rats, named "Sima", is still alive at 44
       | months of age. Sprague Dawley rats have a lifespan of 24 to 36
       | months, with specimens reaching 42 months according to some
       | sources. So Sima, with the help of E5, is extending the limits of
       | the maximum lifespan of Sprague Dawley rats.
       | 
       | The study began in February 2021, when E5 started being injected
       | in 8 female rats every 90 days, with another 8 female rats in the
       | control group. Over time, all the rats in the untreated group
       | died, and in the E5-treated group, all but Sima died.
       | Additionally, Sima has not received any E5 for the last 6 months
       | which may indicate that the benefits of the therapy can become
       | long lasting. She hasn't lost eyesight, hasn't developed skin
       | canker sores, hasn't lost motor function or developed bald
       | patches.
       | 
       | Overall, the treated rats lived longer than the control ones, but
       | it won't be possible to know exactly how much longer on average
       | until Sima dies."
        
       | slowmovintarget wrote:
       | Interesting article on new promise for "rejuvenation" therapies
       | (once the realm of science fiction).
       | 
       | Last paragraph puts its finger on one of the reasons progress is
       | so slow:
       | 
       | > The most promising avenue for rejuvenation (IMO) is not
       | attracting research attention because it cannot attract venture
       | capital; it can't attract venture capital because there is no
       | attractive business model; and there is no business model because
       | of the structure of our patent law.
        
         | amelius wrote:
         | Why can't it attract venture capital if the possible outcome is
         | worth more than what money can buy, regardless of any argument
         | about competition?
         | 
         | Are VCs only interested in wealth that is in excess of other
         | people's wealth?
        
         | sinenomine wrote:
         | It's not just (or even predominantly) patent law: if there is
         | no explicit or implicit agreement for FDA to approve some
         | treatments that modulate ageing (to even become a possibility,
         | this category of indications should be created) and for the
         | healthcare provider complex (insurers, governments, clinics) to
         | provide said treatments to the public, there is no prospective
         | market.
         | 
         | Until there is a coordinated push to align our regulatory and
         | medical systems with this challenge, the status quo will remain
         | frozen.
         | 
         | Will a few remaining decades be enough for the metaphorical ice
         | to crack?
        
         | ericmcer wrote:
         | Would that really dissuade a Musk/Bezos/Gates from investing in
         | it? Our society is flush with billionaires and a procedure that
         | restored youth would be worth 1000X a money making investment
         | to them.
        
           | bryanrasmussen wrote:
           | How do you know they're not investing in it? If they are
           | would it be worth their trying to make money on it or would
           | they consider it worth more if they kept it to themselves?
        
           | sp332 wrote:
           | You can't 1000x investment if there is no barrier to entry
           | for competition.
        
             | epicureanideal wrote:
             | There are other barriers than patents. First mover
             | advantage, brand name recognition, first to achieve low
             | cost, strategic partnerships, etc.
        
             | nonameiguess wrote:
             | They're saying a treatment that can actually reverse aging
             | and prolong lifespan is worth 1000x more than money,
             | especially to someone who already has more money than they
             | can possibly spend in a (currently expected) lifetime.
        
         | gumby wrote:
         | > Meanwhile, the four questions I listed above are not being
         | addressed. Patent law is working against us, since Katcher's E5
         | patent is for a process of extraction. If a subset of active
         | ingredients is identified and the minimal set of rejuvenating
         | proteins becomes known, his patent becomes worthless. Naturally
         | occurring proteins cannot be patented.
         | 
         | > This is the maddening influence of capitalism and
         | intellectual property law on anti-aging science. The most
         | promising avenue for rejuvenation (IMO) is not attracting
         | research attention because it cannot attract venture capital;
         | it can't attract venture capital because there is no attractive
         | business model; and there is no business model because of the
         | structure of our patent law.
         | 
         | This is common in pharma patent law. At an earlier company we
         | made some progress on a treatment for a fairly common disease,
         | but it looked like any compounding pharmacy could make it. So
         | we abandoned that path and went in a different direction that
         | was protectable (and more effective, true). The inverse is the
         | case as well: had the less effective treatment been available,
         | it might not have been worth developing something that could
         | help even more people, because those that needed the better
         | treatment would not be enough to justify development.
         | 
         | But the situation is not as clear as stated by the author.
         | First of all, much of the work is basic research, and that is
         | mostly funded by governments and charities. Second of all, even
         | if you've identified a mechanism of action, developing a
         | feasible _in vivo_ way to trigger that action, figuring out how
         | to manufacture it at scale, and getting it approved can provide
         | many patent opportunities. When people complain  "why are drugs
         | expensive when the government pays for it" they miss the point:
         | "government" developed the transistor,* it was private
         | companies that developed the IC and the microprocessor. The
         | situation with drugs is analogous.
         | 
         | * Yes the transistor was invented at Bell Labs, but Bell Labs
         | only existed due to the structure of the government's consent
         | decree for the Bell telephone company, and when that decree was
         | lifted Bell Labs suffered a precipitous decline. Anyway, it's
         | just an analogy.
        
           | hcknwscommenter wrote:
           | >Katcher's E5 patent is for a process of extraction. If a
           | subset of active ingredients is identified and the minimal
           | set of rejuvenating proteins becomes known, his patent
           | becomes worthless. Naturally occurring proteins cannot be
           | patented.
           | 
           | This is not legal advice, but I firmly disagree with these
           | statements. Individual naturally occurring proteins cannot be
           | patented, but: A method of treating aging by administering
           | the individual protein can be patented. A specific
           | combination (subset) of naturally occurring proteins that is
           | otherwise not really found together in nature in an isolated
           | manner, is likely patentable A highly concentrated extract
           | (or other means of making the particular combination) that is
           | not found in nature is patentable A method of making the
           | combination is likely patentable. A compound that begins as a
           | naturally occuring protein, but is modified in some way for
           | therapeutic efficacy (pegylation, truncation, fusion, etc.)
           | is patentable A formulation suitable for administration (with
           | buffers, stabilizers, etc.) is patentable.
           | 
           | There are many inventions that go into making a therapeutic.
           | Yes the compound itself provides the cleanest and most
           | valuable patent protection, but natural products can be
           | protected.
           | 
           | Then there is regulatory exclusivity, which can be an
           | entirely different ball of wax that does not necessarily have
           | anything to do with patents at all.
        
       ___________________________________________________________________
       (page generated 2022-12-13 23:01 UTC)