Im Professor Robert Doyle in the department of Chemistry here at Syracuse University.
My research is very much focusing on utilizing the vitamin B12 dietary uptake pathway for
drug development. So we are very much interested in exploiting a natural pathway to benefit
humans through drug development.
Right now one of the holy grails of pharmaceutical development is oral peptide delivery. SO normally
if you take an oral medication, its a small molecule thats quite stable to the stomach
acids, or the degrading enzymes in your intestinal tract. But peptides being proteins, that are
being formed as drugs will be degraded and so they typically need to be injected. Insulin
is a classic example of that. Its typically injected of course. And the reason you don't
take an insulin pill is because your stomach and your intestine would degrade it. And so
Vitamin b12, which is a small molecule actually happens to be sensitive to acid hydrolysis
for example. And because you can;t live with out it, your body has had to evolve a mechanism
to recognize it, bind it, protect it through your gastrointestinal system and then carry
it across through your blood stream and let it go. And so what we are trying to do is
use that same system, thats protecting b12 and delivering it, to deliver peptides, by
essentially hiding the peptide in the pathway. And then letting the pathway do what it normally
does. And then when it gets to the side you want it to be on, which is the systemic circulation,
you want it to be able to allow the peptide to work. There is a million reasons why this
won't work and its really complicated, and we don't even fully understand how the b12
pathway itself. But thats what we are really interested in. and the big picture is a greater
understanding of a very impotent pathway biologically and potentially a new route to orally administer
a whole new class of drugs, which obviously would be really, really awesome.
Patients often considerate themselves sicker if they are told they have to administer a
needle as opposed to taking a pill. And lets face it; you eat. Normally the way things
go into your body is through the mouth, so as a consequence taking a pill is not a major
issue. Its a simple, facile thing to do. you get up in the morning, you take your pill,
you go to bed, you take your pill. Injections become, a whole rigamarole. Its a dance. We
are really interested in diabetes because it fits within that paradigm. It fits within
my desire to understand the vitamin b12 pathway and wether it can be exploited to deliver
pharmaceuticals or improve upon existing pharmaceuticals. So looked at in that way, there are only
certain medications that are going to, I believe, work in tandem with the b12 pathway. One of
them, or several them include peptide hormone that are currently FDA approved that happen
to treat diabetes.
We recently just had a paper accepted in the journal Endocrinology, which is been the main
stay of hormone research for really 100 years to the Endocrine society. And the paper itself
essentially describes an effect we were not expecting. So we where doing control experiments,
prior to the oral delivery. So what we needed to do is modify the peptide trying to do the
things I was telling you about, trying to make the peptide work better than it normally
does. And so before we gave it orally, we wanted to know wether it still worked if we
gave it subcutaneously, so with needles. Straight into the system, without having to go through
the gauntlet of the gastrointestinal system. Because if we gave it orally and it didn't
work, we wouldn't know if it was because it didn't work, or it got destroyed.
So we had to bypass the gastrointestinal system and just show that it worked. Or worked OK.
And it turned out, it worked better. So actually this result was born out of us just doing
control experiments, which is obviously a testament to why you should do control experiments.
And actually what happened was, we made it better, which we were not anticipating in
any way, shape or form.
So we got a lot of great data there that will now be a really exciting push for funding.
Also will be the cornerstone now of the oral studies, where we will now translate this
into oral administration and we will see if actually now produce the same effect but given
as a tablet form, as opposed to the need to subcutaneously inject. And that would be a
real milestone in any area of pharmacology. That would be an enormous breakthrough.