Look, scientists are nuts.  Virologists, on the other hand, are certifiably insane.  As Hedwig would say, virologists make the strangest things seem suddenly routine.  Yesterdays absurd future technology (GENE THERAPY!) is now something as miraculous as curing genetic diseases, and as mundane as an anti-smoking therapy.

Todays insane idea?

Using mouse and rat parvoviruses to treat human cancers.

This is not some lone mad scientists mad idea– Though this info was news to me, this approach is being explored world-wide, and is already in clinical trials for glioblastoma multiform.  Yeah, read that Wikipedia article on glioblastoma multiform :-|

most common and most aggressive malignant primary brain tumor

52% of all functional tissue brain tumor cases and 20% of all intracranial tumors

Most glioblastoma tumors appear to be sporadic, without any genetic predisposition.

It is very difficult to treat glioblastoma due to several complicating factors:

  • The tumor cells are very resistant to conventional therapies
  • The brain is susceptible to damage due to conventional therapy
  • The brain has a very limited capacity to repair itself
  • Many drugs cannot cross the blood-brain-barrier to act on the tumor

The median survival time from the time of diagnosis without any treatment is 3 months, but with treatment survival of 1–2 years is common.

We have no idea what causes it. Traditional therapies dont work because its the brain. And once you are diagnosed you are pretty much screwed.

:-|

Enter mouse and rat parvoviruses.

Though you all are probably most familiar with the canine form of parvovirus that is extremely deadly to dogs and puppies, apparently, there are genes in mouse and rat parvovirus that make them a) oncolytic (blow up cancers) and b) oncosuppressive (keep tumors from growing).

When scientists used the rodent parvoviruses against some cell lines in the lab (functionally ‘cancers’) and some animal models of cancer, the tumors stopped growing and/or were killed.

SWEET!

Well there is a good thing and a bad thing about using rodent parvoviruses as cancer therapies.  The good thing is that the viruses dont replicate in humans, which means it would be a pretty safe therapy (especially considering the radiation/chemo/surgery alternatives).  The bad thing is that the viruses dont replicate in humans, which means you cant use them to infect human cancers.  They wont.

Solution?

Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential

Go to our ol buddy, Adeno Associated Viruses.  Stuff em full of rodent parvovirus DNA.  Have the AAV deliver the rodent parvovirus genome (we know AAV loves human cells), the parvovirus genome makes all the anti-cancer proteins, but cant make infectious virus (but wouldnt infect humans anyway), dead tumor.

OF COURSE!

LOL!

I know Im saying this cavalierly, but generating an AAV/parvovirus chimera is not simple.  Viruses are not interchangeable Lego blocks you can take apart and click together.  A lot of effort (a lot of failure) went into generating this chimeric virus on the front end.

But it was worth the effort– the expected result would be that the chimeric AAV/parvovirus could get into tumors the rodent parvovirus could not get into, and the chimera could slow down/kill tumors AAV couldnt slow down/kill.

It did just that.

And more.

The chimera did not just take the good features from its parental viruses.  The new virus was better than its ‘parents’ at executing the desired actions– more cell lysis and lowered cell viability in the tumor cell lines than the parents.  The sum is greater than the parts.

Rat viruses as a putative cancer therapy.  An option for when there are no options, like for  glioblastoma multiform now, might be standard therapy in relatively short order.

Virologists are nuts.

And we are all reaping the benefits of their insanity.

Comments

  1. #1 Bryan
    July 17, 2012

    Any details on the human trial? The BBB isn’t just good at keeping drugs out of the brain; it does a pretty good job of keeping viruses out as well. I wonder how they got around that (intercranial injection?)

  2. #2 daedalus2u
    http://daedalus2u.blogspot.com/
    July 17, 2012

    Abbie, you are just showing how junior a virologist you are and how much you still have to learn.

    Real virologists know that the technique that you use to make chimeric viruses of all types is Homologous Recombinaltion Tiniker.

    With that you can make viruses that are magic and can do anything.

  3. #3 A. R.
    July 17, 2012

    Hmm, this makes me wonder if my viruses (the Filoviridae) could do anything besides kill stuff.

  4. #4 None
    July 18, 2012

    Not much weirder than using Salmonella as either an anti-tumor agent (both as vector for drug delivery or as direct agent) or as a vaccine delivery system. Both techniques are under very active investigation at the moment.

  5. #5 Aj
    July 18, 2012

    Fuck cancer.

    Fuck cancer with rat viruses.

    I think I like that update.

  6. #6 Art
    July 18, 2012

    I get a mental picture of them as Doctor Frankenstein lopping off parts of this, and parts of that, stitching them together, hitting them with a little lightning and the sound of loud maniacal laughter as their viruses come to life and begin to do their bidding. But doing it all on a diminutive scale.

  7. #7 JustaTech
    July 18, 2012

    Well, I’m glad that someone has found something useful to do with mouse parvovirus. From my experience the only thing MPV is good at is making colony managers insane. (It’s super contagious and can wipe out your whole colony or even a whole facility if you aren’t monitoring properly.)

  8. #8 Bob Powers
    July 18, 2012

    Interesting times, for sure.

  9. #9 Justicar
    July 19, 2012

    I look back on where I’m from
    Look at the virus I’ve become
    And the strangest things seem suddenly routine
    I look up from my Vermouth on the rocks
    The gift wrapped ERV still in the box
    A Mendelian disease

  10. #10 Justicar
    July 19, 2012

    Oh, <3 for the Hedwig reference; I haven't watched that in forever – watching it now. =^_^=

  11. #11 John
    July 20, 2012

    Oh man, there were some recent meeting minutes of an FDA committee where they were discussing something along these lines, it was wild stuff. It was kind of depressing though since the authors were getting called out for making weasel-word statements on things being ‘likely’, ‘less likely’, etc.

    Discussion of Human Gene Transfer Protocol #0904-976: A Phase I Ascending-Dose Trial of the Safety and Tolerability of Toca 511 in Patients with Recurrent Glioblastoma Multiforme
    http://oba.od.nih.gov/oba/RAC/meetings/jun2009/RAC_Minutes_06-09.pdf (bottom of pdf p. 29 is where discussion starts)