AI joins the search for new TB drugs

4 February 2020

Ulrika Simonssons research team constructs mathematical models that can predict which drugs and doses will be most effective and give least side effects.

Tuberculosis is once again a major public health threat as the causative bacteria become resistant to antibiotics. Globalisation is also contributing to its increased spread. Professor Ulrika Simonsson of Uppsala University has received an EU grant to develop new antibiotics against tuberculosis with the aid of mathematical models.

“Many people believe that tuberculosis is something we no longer suffer from here in Sweden; however, the situation has changed. Due to resistant bacteria, today tuberculosis is a disease that affects us all. The drugs no longer work because the bacterium has changed and become resistant to many and sometimes all available antibiotics,” says Ulrika Simonsson, professor of pharmacokinetics at the Department of Pharmaceutical Biosciences at Uppsala University.

Last year saw the first death in Sweden from the disease as a result of resistance leaving doctors unable to find a cure but, of course, there are many countries in which the situation is much worse. The United Nations has raised the problem to a political level, while the EU is investing many of millions of euro in developing new antibiotics.

The new European Regimen Accelerator for Tuberculosis (ERA4TB) – in which Uppsala University is a stakeholder – is a public-private initiative to develop new drug combinations to combat the threat from resistant tuberculosis bacteria.

Mathematical models identify the correct dose

Ulrika Simonsson, professor of pharmacokinetics
at Uppsala University.

Ulrika Simonsson, who is leading research at Uppsala University, has received a grant of SEK 18 million over the next six years. Her research team constructs mathematical models that can predict which drugs and doses will be most effective and give least side effects.

“We collaborate with those conducting preclinical trials, integrating all of the data into the model so that we can choose the right drug and optimal dose in a kind of virtual clinical trial,” explains Ulrika Simonsson.

By today’s standards, currently available drugs are ineffective and a new, faster-acting and safer therapy is required to reduce the length of treatment and overcome the threat of drug-resistant strains. 

The challenge is to treat tuberculosis not with a single drug but a cocktail. While the traditional method has been to test one drug at a time, this project will test several simultaneously in order to see how they affect one another.

What are the advantages of using computer models and artificial intelligence (AI)?
“During development, a drug it will be tested on a limited number of patients who may not be representative. We are now able to collect data on more patients on an ongoing basis and refine it so that the model is continuously updated and improved.”

The research team also develops models to predict the optimal dose for each individual patient based on factors such as age, gender and kidney function. The aim is that, in future, doctors will be able to download an app to their phone that proposes specific individual doses.

Antibiotics overused

The problem of resistant bacteria is not limited to tuberculosis; rather, it is part of the growing problem of antibiotic resistance that can be traced to overuse and often improper use.

“There has been a change in society and awareness is increasing but in many European countries it is still easy to obtain antibiotics,” says Ulrika Simonsson.

Uppsala University is also involved in the newly launched EU Collaboration for Prevention and Treatment of Multi-Drug Resistant Bacterial Infections (COMBINE), which is being coordinated by Anders Karlén. This is a multinational collaboration of 11 partners from academia and the private sector with the goal of progressing the development of new antibiotics.

“The collaboration between Combine and ERA4TB will strengthen Uppsala University's role in the world around these issues. There is also a third consortium to identify new potential drugs. Together, these three consortia are part of the Innovative Medicine Initiative's (IMI) Antimicrobial resistance (AMR) Accelerator Program.This is an enormous investment in an emergency situation. It will be exciting to play a role in a greater, European context,” says Ulrika Simonsson.

 

 

 

 

 

 

 

 

Facts

According to the World Health Organization (WHO), an estimated 10 million people contracted tuberculosis during 2018, 1.6 million of whom died. Even if the incidence of tuberculosis decreases, the drug-resistant strain will continue to present a growing threat to the global population. The UN has a stated goal of ending the tuberculosis epidemic by 2030 through joint measures from its members.

Universities and companies are collaborating in the EU consortium ERA4TB to hasten the development of new tuberculosis drugs. The consortium was launched on 1 January 2020 and includes 30 partners in 13 countries. Behind the investment is the Innovative Medicines Initiative (IMI) – a partnership between the EU and the European Federation of Pharmaceutical Industries and Associations (EFPIA).