In the last few years, since the Prion
was accepted as the agent of infection for TSEs
by the majority of the scientific community, a number of research
programs have begun in order to study how the infection is transferred
from animal to animal and, in light of the BSE
epidemic, from species to species. Most of the research done so
far has used lab mice to create murine models,
other species being avoided for ethical and time constraint reasons
(incubation of the disease takes a much shorter period in mice
than in most other animals).
This research has found that the species barrier affects the transmission
of TSEs in a very significant way
with the transition between species being up to one million fold
harder than simple same species transfer. Through use of murine models
the minimum levels of agent needed
to transmit the disease were accurately measured and this was
found to be a constant between animals of the same species, known
as an infective unit. This
constant has been measured at hundreds of thousandths of a gram
of infective agent, and the nervous
tissue of a TSE sufferer is thought
to contain between one and ten thousand million IU
per gram. Going by these figures even the agent
contained in 1g of infected brain is enough to bring on a TSE,
even across the species barrier!
Further work on the species barrier
has been done using transgenic mice
and other animals to study the speed and ease of transfer between
species, and especially in resent years the properties of BSE.
One worrying discovery in this research is that once a strain,
such as scrapie, crosses a species barrier
the new strain that it becomes
is now able to cross species barriers
that the original found too difficult. A well as this BSE
appears to be unable to cross few species barriers.
For example scrapie has a very
limited range of other species that it can effect, cattle being
one of these. But once scrapie
becomes BSE in cattle it can then
go on to infect a huge range of species relatively easily, creating
new strains such as ZSE,
FSE and a new variant of CJD.
Other research has found is that the possibility of transfer of
a TSE is governed by a gene that controls
PrPc production (chromosome 20 in
humans) and is almost identical across most species, slight variances
leading to different glycan configurations
on PrPc. This was born out with a
series of experiment done using lab mice, hamsters and transgenic mice
with the hamster PrP gene. The results
show that in transmissions from mice and hamsters infected with
the respective TSEs the transgenic mice
performed identically to the hamsters in their susceptibility:
Coupled with this is the conclusion that transgenic mice who have
the PrP gene removed are completely
asymptomatic and are not affected by, or do not even become carriers
for TSEs. The lack of this gene,
and consequently PrPc, has not appeared
to cause any noticeable side effects in tests so far although
scientists are still not certain that there will be no long term
effects, or whether PrPc does have
an important function in animals other than mice. However this
result does give the possibility for future genetic immunisation
against TSEs by removing the PrP
gene.
Scientists have also studied the way in which the Prion
enters the body of mammals in order to comprehend the dangers
of transmission to humans of BSE
and other future TSEs that may appear
(Scrapie, having been around
for centuries is known not to be able to cross the species barrier
to humans). Researchers already knew that a TSE
could be transmitted by feeding through their experience with
Kuru, but the exact method by which
the agent entered the body without being digested was uncertain.
The first obstacle that the Prion
has to surmount is the gastric juice which contains enzymes to
destroy protein, but it is known that this mechanism sometimes
leeks allowing through between one in a million and one in ten
million protein molecules, this is accentuated during illness
or after drinking alcohol. The Prions
is then thought to leave the gut via part of the immune system,
the Peyers Patches. These are small nodules scattered over the
inside of the intestines, with an outer layer of specialised cells
that are very good at absorbing bacteria, proteins and viruses
from the gut. This is used by the body to detect organisms and
molecules that the immune system needs to be aware of. From here
the route of the Prion is thought
to lead it through the tissues surrounding the gut, and then into
the peripheral nerves, through which it travels up to the brain;
although this route is not known for certain, and it is not known
whether the body contains any special measures to protect against
the passage of Prion diseases.
Only once the Prions reach the
brain can the disease begin.
