Partner content |  Success of mRNA vaccines could serve as a blueprint for treating other diseases

Partner content | Success of mRNA vaccines could serve as a blueprint for treating other diseases

For countries that can get their hands on it, the rapid development of mRNA vaccines for COVID-19 has been nothing short of a miracle, saving an estimated 1.1 million lives in the United States alone.

By taking advantage of recent advances in gene sequencing, chemical synthesis and novel delivery mechanisms, scientists were able to start the first clinical trials of mRNA vaccines just four months after the World Health Organization declared a pandemic. Industry watchers say this success could serve as a kind of blueprint for tackling other hard-to-treat diseases.

“It’s been developing so many technologies together that has put us in a position where we can respond very, very quickly,” says Richard Pozzato, MaRS Senior Health Adviser. “He showed that we can do it.”

Researchers are using these advances to accelerate all aspects of drug development — from discovery to how a drug is administered — with the potential to cut costs, save time, and help more patients. “The whole goal here is to be able to treat as many patients as possible,” Buzzato says.

Using artificial intelligence to accelerate drug development

Less than 10 percent of new compounds go from test tube to clinical use. Most of them turn out to be either less effective or more toxic than originally thought. However, many of the approved medications can have serious side effects.

For now, the discovery and development process has “crashed and failed,” Buzzato says. “You do an experiment and you see what happens. Then you discover something you weren’t expecting.” This is where AI and machine learning can help: By running tests through computational models, they can identify problems as well as promise new vehicles faster.

“If you can combine the speed of computational methods with the intuition and intelligence of the human brain, you can start asking different questions for a different problem,” says Nahid Korji, co-founder, president and CEO of Cyclica in Toronto. And that means more medicine, and better medicine – faster. We won’t have to wait 12 years to get it.”

Researchers have developed computational techniques to identify molecular drivers of disease for more than 20 years, but the area has expanded dramatically in the past five years as more genetic data has become available. A major breakthrough came last year when Google’s DeepMind AI company allowed free access to its AlphaFold database of 3D protein structures.

The software predicts these structures with more than 90 percent accuracy – twice as accurate as previous programs. Bogato says that work that would have taken months or years can now be done in a few hours or days.

More than 400 companies worldwide are now working in this field, targeting diseases from Alzheimer’s and Parkinson’s to various forms of cancer. Cyclica is looking for new treatments for a range of hard-to-treat ailments, including some central nervous system disorders such as pain and spinal disease. Deep Genomics, another Toronto-based project, is preparing the first drug programs discovered by artificial intelligence for clinical trials.

Finding a better delivery mechanism

Medicines are only effective if they end up in the right place at the right time. When they are on target, they can treat disease in affected tissues with minimal side effects. Researchers have been developing safe and effective drug delivery techniques for decades, but new and more complex therapies such as mRNA and gene editing need more complex delivery systems. This is where lipid nanoparticles come in.

Lipid nanoparticles are the tiny envelopes that provide the active ingredient in COVID mRNA vaccines. Their success in mRNA vaccines indicates that they have much greater potential to safely deliver other innovative treatments, such as small drugs, proteins or genetic material.

“Seeing the safety and efficacy of these vaccines was evidence that you can use this in a new way to deliver gene therapy,” says Brent Stead, co-founder and CEO of Specific Biologics, a discovery-stage gene-editing company that tests lipid nanoparticles. “If it works in this app, there is no fundamental reason why it can’t work with others.”

The particles, lipid molecules that closely resemble human cells, act as a protective layer for small molecule therapies as they make their way to target cells. Their close resemblance to human cells means they can evade the body’s natural defenses, making them non-toxic. They are particularly effective at reaching specific organs or cells because they can have chemical structures attached to their surface that recognize unique molecules on their targets.

Researchers are looking to see if lipid nanoparticles can be used to deliver CRISPR gene-editing technology to target rare diseases caused by a single genetic mutation, such as ALS, Huntington’s disease and blinding eye diseases. “You can imagine a treatment where you do the treatment once and permanently correct the disease,” Stead says.

California-based Intellia Therapeutics recently started the first clinical safety trials using this combination to target liver disease, and Specific Biologics conducts lab research on diseases that affect the lungs, such as cystic fibrosis.

However, treatments are still several years away. Although CRISPR technology works in animal models, researchers are still figuring out how to make it consistently target a specific genetic mutation without harming other cells. Another challenge, Stead says, is the fact that lipid nanoparticles tend to accumulate in the liver, making them more effective at targeting liver disease. Biotech companies are now working on the next generation of LNPs that target different tissues and organs.

Create a customized treatment

One of the challenges in cancer treatment is that cancer cells are constantly looking for ways to survive. They may initially respond to treatment but then turn and develop resistance. Doctors then need to find a new treatment. In other cases, patients do not respond to treatment at all. Scientists are turning to next-generation sequencing to find the treatment that can be customized to the individual patient, as well as identifying the cause of treatment failure.

Xue Wu, co-founder of Geneseeq, a company that specializes in the field, remembers one woman who had not responded to conventional chemotherapy for advanced sarcoma and was working on life support devices in an intensive care unit. Using next-generation sequencing, Wu discovered that a rare genetic mutation may have caused the resistance. I helped her join a clinical trial for a new drug targeting that mutation. Within 10 days, the tumor had shrunk dramatically, and the woman lived for another 10 months before she developed drug resistance to this drug and died.

Next-generation sequencing can map hundreds of genes at once and find the mutation in as little as five days, so doctors can find treatments that target just those cells. Since the US-based Foundation for Medicine made this technology commercially available a decade ago, its application in the US and other countries has grown rapidly. Wu says the technology is particularly useful in treating lung cancer, where several generations of precise treatments are available. “You have the option of choosing different drugs, so the patient will have a long life. It greatly improves the five-year survival rate for these patients.”

The next frontier, Wu adds, is developing more precise treatments for other types of cancer mutations currently without viable treatment options. Researchers are now looking into the possibility of deploying technologies such as CRISPER gene editing and mRNA vaccines.

Expanding the range of treatments

Another big challenge for Canadian companies accelerating drug development outside of the lab, is in the commercial realm, Pozzato says. The success of COVID vaccines has proven that many Canadian researchers are pioneers in drug development. For example, Peter Collis, professor emeritus at the University of British Columbia, was one of the pioneers in developing lipid nanoparticles. Genevent Sciences Corporation in British Columbia is supplying LNPs to two mRNA vaccine manufacturers, Pfizer-BioNTech and Moderna.

However, as a recent report from the Council on Innovative Economy notes, Canada does not currently have the large-scale manufacturing facilities that can help translate local research into local remedies. The federal government has begun to address this problem, investing $1.2 billion in various projects, which can help Canada secure a slice of the growing global biotech industry.

The Health Impact MaRS The conference, which will take place from May 25-27, explores the latest innovations in biotechnology.

Anita Eilash is a freelance writer who writes about technology for MaRS. Torstar, the parent company of the Toronto Star, has partnered with MaRS to highlight innovation in Canadian businesses.

Not giving an opinion This content has been produced as part of a partnership and therefore may not meet the standards of impartial or independent journalism.

2022-05-13 19:18:05

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