Profile: Bacteria’s natural born killers
Winning the 2008 NSW BioFirst Commercialisation award has
come at exactly the right time for Special Phage Holdings, which has treated a
patient in the clinic and is currently looking at a second round of private fundraising
to develop its portfolio of bacteriophages
02/10/2008 16:45:00
Australian Life Scientist
By Kate McDonald
Just before Christmas last year, a 60-year-old patient at Westmead Hospital got
some good news. The woman was suffering from a chronic infection that nothing
could shift.
Pseudomonas aeruginosa had taken up residence in her bladder and all of the
available antibiotics proved useless. She was facing a decision: radical
surgery or a new therapy that has been rarely tested in a western
hospital.
She opted for the latter. Over five days just before Christmas 2007, she was
infused with a cocktail of bacteriophages through a catheter. Bacteriophages
are viruses that infect bacteria and represent the most prolific organism on
the planet.
Phages are natural born bacteria killers and are nature’s solution to keeping
bacteria in check. They are ancient, they are everywhere and there are an
estimated 1031 of them in existence.
The patient began to feel better within a couple of days and was home for
Christmas. Six months after her treatment, she remains infection-free.
Not only was this good news for the patient, but good news for the private
Sydney company that is developing bacteriophage therapy, Special Phage
Holdings(SPH), run by Dr Tony Smithyman.
Phage therapy is nothing new of course, having been used extensively in the
countries of the former
Smithyman and his team at SPH have been investigating phage therapy for the
last five years. They have managed to refine their technology for collecting,
screening and growing phages, and now have a library of several hundred, all
specific to particular bacteria and even specific to strains of bacteria.
“They are commonly found in soil, water, plants, sewage, mud – anywhere there
is bacteria that they can go and eat,” Smithyman says.
“The question is, how do you get them? You’ve got to go looking for them in the
most appropriate places, which means a lot of interesting times. For instance,
we go looking in Manly lagoon and Hubert (SPH’s marketing manager, Hubert
Mazure) has been on a sewage mission.
“However, you have to have the right systems to extract the phages. There is
quite a lot of skill involved. It’s a bit like looking for monoclonal
antibodies – you have a target and then you screen. And the longer you go the
better you get.”
Bacteriophages come in two forms: lytic and lysogenic. Lytic phages have
evolved purely to destroy bacteria, Smithyman says. “There is no messing around
with them. They go straight in and destroy the bacteria, and because of that
they have fairly small genomes.
“The lysogenic phages have evolved to live with the bacteria, so they have
larger genomes and have a different lifecycle. They can transfer toxin genes to
the bacteria, so one of the things we have to do in phage therapy is have a
system for screening to make sure you don’t have the lysogenic ones.”
Smithyman recently returned from a phage conference in
“They are looking at using phages for delivering vaccines, a lot of work on
using phages for purification and more genetic work coming through to help
understand the molecular biology. And then there is the clinical work. A lot of
that is very interesting. It is an intrinsically fascinating topic.”
Classification and commercialisation
One of the issues phage therapy will face in the future is its categorisation
for human health purposes. There are already phage therapy products on the
market, but they are for plant health and to treat foodstuffs such as meat and
cheese.
Those products were approved by the US FDA as Generally Regarded as Safe
(GRAS), and this designation is expected for any future phage therapy product
for humans.
“When it comes to treating patients, they aren’t a pharmaceutical so there is a
lot of discussion around the world as to where they actually sit,” Smithyman
says. “It may be that they will end up in their own category.
“They are extremely safe with no side-effects and no toxins, so there is no
real need to go through animal studies, but the jury is still out on how they
will be classified. It will probably be as a biological, not a chemical, but
they might have to have their own category.”
Special Phage Holdings is one of a number of companies planning clinical trials
for phages. The therapy has been used in parts of
Smithyman says there are several American and
This is why both the successfully treated patient and the BioFirst
Commercialisation award have come at exactly the right time for SPH. Smithyman
says his company is at the stage of developing cocktails of phages for prototype
products and was planning for the trial stage when the patient at Westmead came
up.
SPH has strong research links with both Westmead and
“We are planning trials now and working on the protocols,” he says. “We have
three trials planned – one in Australia, again through Westmead and Royal North
Shore; one overseas; and one a veterinary trial, also here in Australia.”
The company is also undertaking a second round of fundraising, approaching the
group of original shareholders who provided the initial seed money, as well as
sophisticated private investors and select corporate investors. The NSW
Government award has come as a nice bit of publicity at exactly the right time,
Smithyman says.
“We are going to be able to use the award to travel, there is some legal and
patent advice and some accounting advice, as well as PR, so we’ll use them all
very judiciously. It has come at exactly the right time.”
Broad spectrum delivery
Smithyman foresees a time when broad spectrum phages will be developed for
immediate use once a patient presents with an infection. He also sees a time
when patient-specific phages are produced for particular infections.
“If it is extremely urgent they will be hit with a broad spectrum, but before
that you take a swab and isolate the type of infection, take that isolate and
run it past a vast collection of phages, choose the right one and then grow it
up quickly. In a couple of days the patient can be treated with their own
specific phages.”
Delivery options are as versatile as the phages, he says. “The patient at
Westmead was infused because we had to decide how to get the phages into the
bladder, so a catheter was chosen. But normally they would be used in liquid
form embedded in bandages, or as a tablet for straightforward oral delivery. We
have also formulated a cream, and another way they will be used is through a
nebulliser.”
Phages are extraordinarily powerful but obviously they won’t cure everything,
particularly if there are co-morbidities. And they probably will meet the brick
wall of bacterial resistance, just as antibiotics have done.
“That’s why we are developing cocktails – bacteria might become resistant to
one type of phage, but not to many.”
And the market is potentially huge. As Smithyman points out, the large
pharmaceuticals have been walking away from trying to develop new antibiotics
over the last couple of years because there isn’t much profit in it, leaving it
up to the smaller and generic pharma companies to look for biotechs to come up
with novel ideas for antibiotics.
It is a $24 billion a year sector that is becoming a vacuum, he says, and
perhaps phages are the right organism to fill it.
end
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