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.
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.
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.
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.
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.