Fat is a tricky issue. We know the world is getting fatter: in 2016 the World Health Organisation reported that 650 million adults were obese, almost three times as many as in 1975.
But we don’t have many ways of treating it. Appetite-suppressing drugs have come with side effects including addiction and hypertension. Surgery is scary, expensive and has its own set of side effects. The oldest treatment – gentle advice on diet and exercise – has proven ineffective. The NHS spent £6.1bn on obesity and related conditions – from joint and muscular pain to diabetes, heart disease and various cancers – between 2014 and 2015, more than the cost of the police, the fire service and the judicial system combined.
The problem is that we still don’t fully understand the causes behind obesity, a mix of psychological, hormonal and genetic factors that mean some are more predisposed towards it than others.
Zandy Forbes, who has worked as both a fruit fly geneticist and hedge fund manager, is most interested in that last part of the formula. Forbes is the founder and CEO of MeiraGTx, a gene therapy company that has developed technology that could one day allow those looking to lose weight to “switch on” a combination of genes that produce the hormones and peptides that “control your appetite, your stomach emptying, your satiety, your glucose, your fat”.
Gene therapy is the process of either correcting a “broken” gene in the body or inserting a new one that’s missing. Using currently available technology that requires regular, often painful, injections. With obesity it’s even more complicated because the hormones that control it are numerous and difficult to synthesise: many are so unstable that they don’t last for more than a few seconds once they’ve been made.
Forbes claims her company’s technology will change this. “What we’re able to do is take any gene, for any drug that’s currently available, or that has never been turned into a drug,” she says. Rather than injecting synthetic hormones, they would inject a gene that tells the body to make those hormones itself. A further medication, delivered as a pill, activates the gene.
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A recently released “wonder” drug, Wegovy, has been hailed as revolutionary because its creators have managed to synthesise a highly unstable hormone called GLP-1, which helps to release insulin, thus controlling blood sugar. Wegovy is effective, but not without its problems: users, who are given a weekly injection, have reported massive weight loss but also a “morning sickness” side effect.
Forbes says that, so far, the drug her team has created has not only combined GLP-1 with two other hormones that control factors relating to obesity, but also allows the body to create the hormones naturally when they are needed, rather than having an artificially long-lasting synthetic hormone.
“We can make the combinations that your body would make… and then only switch them on when you take a pill,” says Forbes. “This allows you to control the dose and the timing of things. And you don’t have to alter it to make it long-acting, because your body’s making it when you need it.”
The technology could have applications across many areas of medicine, from treating cancers to degenerative diseases including ALS, Parkinson’s and Alzheimer’s. “Once you’re able to make the body make any protein you want, at any time, you start to be able to understand how you can use this technology for things that can’t be done now,” says Forbes.
A final, marketable version of the pill is still about ten years off. “We’ve done this in animals, we’re starting to do it in non-human primates, monkeys,” says Forbes. “Our aim is to start the phase one safety studies next year.”
To fund development, MeiraGTx has taken the unusual step of working with Moorfields Eye Hospital in London and the pharmaceutical behemoth Johnson & Johnson on more traditional gene therapies for inherited progressive eye disorders. The results are promising.
“We literally take the gene, manufacture it in a little ‘spaceship’ made of proteins, and then you inject it under the retina,” says Forbes. “These guys can start to see in the dark and be independent, and feel that they’re not going blind. And hopefully, they don’t go blind.” Three storeys below Forbes’s office, across the road from Moorfields, is a facility where the drugs for the trials are manufactured: all long corridors and fluorescent lighting, with alarming signs warning that viruses – inactive, the guide clarifies – are being used.
With such breakthroughs at stake, Forbes, who ran the hedge fund Sivik Global Healthcare before she and her colleague Rich Giroux founded MeiraGTx in 2015, says pharmaceutical companies get a raw deal. “It’s very, very, very expensive to make these technologies and these drugs, and really, really risky,” she says. “For every drug that a billion dollars gets spent on, there are 20 drugs that a billion dollars were spent on and they failed. So really, [each drug is] costing $20 billion.
“Who pays for this technology to be developed? Who paid for Moderna to make RNA technology, which helped save the world from Covid, arguably? It was a VC fund. And if we don’t address pricing in a thoughtful way, there will be no investment and new technology.”
Without that funding, she argues, her technology wouldn’t be viable. Profit has to come into the equation. “The discussion of the pricing isn’t as simple, in so many words, as ‘pharmaceutical companies get loads of money’.”