13 Jan 2020

HOW GEORGIAN PHAGE SCIENCE MIGHT PAVE THE FUTURE OF BIOTECH

With the world’s largest library of classified bacteriophages, Georgia is in a unique position to take advantage of its knowledge and experience in a field of science still getting on its legs in the West and elsewhere

Ernie Whitman Piper IV

While the world races to develop new antibiotics in a race against increasingly resistant bacteria, the cure to the world’s next epidemic might just be found tucked away in a lab in Georgia.

The key here is not, however, a breakthrough in antibiotics, but a collection of disease-devouring viruses, otherwise known as phages.

In 1923, Georgian doctor Giorgi Eliava returned from his studies in France and established a new sort of bacteriology laboratory in Tbilisi: one that would find and categorize these microscopic, disease-devouring creatures his colleague Félix d’Hérelle had discovered some years earlier – bacteriophages.

Given little attention in the West, where antibiotics had already gone into widespread commercial production by the 1940s, phage-based therapies and treatment options have been available in the countries of the former USSR for decades.

Now, nearly 100 years after being brought to Georgia, phage science is putting Georgia at the forefront of a coming revolution in the biotech industry.

The Phage future

Modern medicine relies heavily on antibiotics, not least because they treat infections, but also because they prevent them, without which modern surgery would be practically inconceivable.

Antibiotics, however, have an Achilles’ heel: bacteria are already developing resistance to our strongest drugs. The World Health Organization considers antibiotic resistance one of the biggest threats to global health, food security and development today.

Unfortunately, the creation of new antibiotics takes too long and is too costly.

“Less and less money is going into the development of new antibiotics as they are less lucrative,” says Dr. Sandro Sulakvelidze of Intralytix, a US-based company working on a solution to this problem.

“People take antibiotics once a year – if that. The pharmaceutical industry is investing in other medicines, as other medicines are needed every day. It does not make financial sense to invest in antibiotics.”

But it does make sense to invest in phages – the microorganisms which Dr. Eliava began cataloguing and collecting in Tbilisi almost 100 years ago.

Bacteriophages, read, “bacteria-eaters,” are viruses.

The viruses we are most familiar with are things like influenza, which infect our own cells, but phages instead hunt and kill bacteria themselves.

“They have little legs which are encoded to attach to certain bacterial cell walls. When they grasp onto them, they act like a key to ‘open’ that bacteria”, Head of Business Development at BioChimPharm Rati Golijashvili told Investor.ge.

“They then inject their own DNA, and turn the bacteria into a phage multiplier factory, and then the phages burst the bacteria and hundreds of phages come out.”

However, just as bacteria come in many shapes, sizes and virulencies, so do phages.

To treat a bacterial infection with phages, one must use the correct cocktail of phages which will target a particular kind of infection. This is why it is important to have a living database of viruses to fight known diseases, and know which petri dish to “check out” from the library, so to speak.

The Eliava Institute in Tbilisi has the world’s largest library of known phages, and their staff have been producing commercially available phage drugs for the countries of the former USSR for decades.

“Our institute is one of the pioneers in phage study and phage therapy. Even today, the institute is considered the center of phage science, personnel, and know-how in bacteriophages,” Mzia Kutateladze, the director of the Eliava Institute, told Investor.ge.

“Nowadays, phage research has become very active in the EU, US, China and other countries, and the scientists have to try to reinvent the wheel, and spend a lot of money and time in doing so. This is where Georgia has an important role to play, and can help in the development of phage science abroad”, Kutateladze adds.

Late bloomers

Despite their efficacy, phages have still not received much attention in the west.

Dr. Sulakvelidze points at two reasons for this: the ease of the use of broad-spectrum antibiotics, and the old prejudice that phages are remnants of “Soviet medicine.”

Sulakvelidze founded Intralytix in Maryland to help bring the well-known phage science of Georgia to the West.

“When we started the company, no one knew what phages were, no-one knew how to approve them, regulate, patent them, so it was next to impossible to develop them for human therapy at the time,” he says.

He and his team chose to market food safety products before human or animal drugs. Intralytix boasts the largest portfolio of FDA-approved phage products on the US market: a series of food-safety aerosols to kill contaminants like E. Coli or Salmonella.

“Food safety is easier as 100% of non-processed fresh food already contains billions of phages. They can also contain bacteria that trigger illness. Food-born illnesses are a significant problem. The phages occur naturally in food, so you are not genetically modifying, you are just picking one that occurs naturally and spraying a little more on.”

Another issue of developing and promoting phages is securing a patent.

“When you patent a phage, you can only patent the manner of application and formulation. It is a limited protection, as someone can isolate another phage and do the same with other phages”, Sulakvelidze says.

Moving further afield

Sulakvelidze estimates that the market for food safety phage products will plateau at $50 million in the US. But the more significant potential market is in drug development, with ramifications for fields as diverse as women’s health and industrial agriculture.

Though progress has been slow, Kutateladze says the Eliava Institute has already made inroads with international organizations looking at applications for phages. “We’re supplying some German farms with phage preparations for poultry and veterinary applications, also we are working on phages for aquaculture,” she says. “We have a lot of scientific collaboration via joint projects, we are participating together with six countries in Horizon 2020 project, and recently we started cooperation with two big companies in Switzerland and the US.”

Sulakvelidze agrees with the potential.

“Researchers are looking for links between microbiomes and obesity, cancer, alzheimers. There are all kinds of links. Once the links are established, then how do you intervene? Hypothetically, you find Bacteria X responsible for Alzheimer’s, and try to eliminate it. With antibiotics, you end up destroying the entire biodome. While with phages, you can be more selective and purposeful in what you target.”

In Georgia, there is already a significant knowledge base in terms of personnel and phage samples; home-grown BioChimPharm already offers a number of products to treat bacterial infections such as Streptococcus, Staphylococcus, E. Coli and other horror stories. However, the infrastructure to develop, test, and manufacture phage drugs on a large scale is still lacking. Other countries are catching up, leaving questions whether Georgi a will maintain its leg up.

“The global phage market is still in an infant stage,” says BioChimPharm’s Rati Golijashvili, “but in 5-10 years there will already be a lot of markets and products that will be popular and well-known”.

Rolijashvili predicts that the future of phage science will likely entail a synthesis of Georgian know-how with foreign capital and access to markets.

Kutateladze agrees that time is ticking for Georgian labs.

“In Georgia, we have built and operated everything by ourselves. We still have high recognition and respect from outside of the country. Now we must make use of this advantage, and find reliable partners with whom to make the ‘jump’ forward.”

Sulakvelidze is optimistic about Georgia’s potential in attracting foreign partners.

“The Eliava Institute is very well known. With some additional state support to upgrade the local infrastructure, support clinical trials and develop additional products…we could eventually even see phage products coming directly out of Georgia onto foreign markets.”

 

Source: http://investor.ge/article.php?art=6