Fractyl Health is developing an alternative gene therapy to drugs such as Ozempic and Wegovy to control blood sugar and body weight without repeated injections.
The semaglutida, the drug originally developed for type 2 diabetes and now prescribed as a drug medication under the Ozempic and Wegovy brands, has an important inconvenience: people usually stop taking medication.But what if the drug only had to administer once to obtain lasting benefits?
That is the idea of treatment for type 2 diabetes of Fractyl Health, which could also be used to control weight.This biotechnological company based in Lexington, Massachusetts, in the USThe semaglutida."There is the problem that you have to continue with the therapy to be effective," says Harith Rajagopalan, Training and CEO cardiologist and Co -founder of Fractyl Health."That is the Achilles heel," he adds.
a drug that removes hunger
Ozempic and Wegovy, which are administered in weekly injections, mimic a human hormone called LPG-1, which is released in the intestine in response to food intake.One of the functions of LPG-1 is to incite the pancreas to produce insulin, which regulates blood sugar.In type 2 diabetes, the pancreas does not produce enough insulin or resists it.This causes an accumulation of blood sugar that, over time, can cause permanent damage to the eyes, nerves, kidneys and blood vessels.
The LPG-1 also interacts with the parts of the brain involved in the appetite and indicates the feeling of satiety.This is how the semaglutida leads to weight loss.People who take the drug tend to have less cravings and eat less.
But drugs are expensive and can have side effects such as nausea, diarrhea and constipation, factors that make some people leave time treatment.Others may accidentally skip, or simply stop taking them when they reach their weight loss objectives.But when these treatments are interrupted, blood sugar levels increase, the appetite returns and, often, the kilos.
Rajagopalan hopes to avoid this with a unique treatment that lasts years.The company wants to introduce into the pancreas an artificial gene that produces the GLP-1 hormone continuously, without the need for weekly injections.The method, called gene therapy, uses inactivated virus to transport a therapeutic gene to pancreatic cells.Virus are used due to their natural ability to transport genetic material to cells.
medications that reduce glycemia and weight
Until now, Fractyl has only tried this method in animals.Company scientists wanted to verify to what extent gene therapy could reduce the glycemia in fasting, an indicator used to detect diabetes.Using mice, raised to develop type 2 diabetes, they administered a single infusion of gene therapy to a group and weekly injections of semaglutida to another.After 10 weeks, they verified that gene therapy reduced fasting blood glucose by 70%, more than the semaglutida, which achieved a 64%reduction.
The company's scientists presented the results at the Congress of the American Diabetes Association, held at the end of June, along with other results according to which the therapy also reduced the body weight of mice by 23% compared to miceof control.
The weight loss wasSurprising, Rajagopalan stands out.Ozempic and Wegovy are injected into the adipose tissue of the thighs, at the waist or at the top of the arm.From there, they enter the bloodstream, where they somehow communicate with the brain.Since Fractyl gene therapy is managed directly in the pancreas, company scientists did not expect significant weight loss.
An explanation is that gene therapy is producing enough LPG-1 in the pancreas so that a part enters the circulatory system and communicates with the brain, says Daniel Drucker, endocrinologist and professor of Medicine at the University of Toronto.Another possibility is that there is an unknown signaling mechanism in the pancreas that indicates to the brain that stops eating.
gene therapy is expensive
To administer therapy in the pancreas, the company developed an endoscopic procedure that consists of threading a fine needle, together with a catheter, which descends through the throat to the gastrointestinal tract.Fractyl scientists tested the security of the procedure in 50 pigs, whose pancreas is anatomically similar to the human.The team confirmed that the procedure successfully administered gene therapy to pancreatic cells, but did not verify whether it caused changes in blood glucose or in the weight of pigs.No adverse side effects on animals were observed.
But Drucker is skeptical of the possibility of injecting a therapy directly into the human pancreas."The pancreas is a very fragile and important organ," he clarifies."If you click ... you can induce inflammation."
In addition to producing insulin, the pancreas manufactures digestive enzymes that help break down food.But when it becomes inflamed, a condition called pancreatitis, these enzymes can attack the pancreas.Pancreatitis can be short or chronic, and the latter is able to cause permanent damage to the organ.
Gene therapy could be a expensive method to treat diabetes.Several gene therapies for other diseases already exist in the market, and its price is in the clouds.One of them, which treats a blood disorder called beta-caasmia, costs 2.8 million dollars.Another, for hemophilia B, costs 3.5 million dollars.
María Escobar Vasco, endocrinologist and expert in diabetes of UT Health San Antonio, points out that the idea of a unique gene therapy is intriguing, but that more evidence will be necessary."The question is: is it sure? I think we still don't know," he says.The objective of the company is to initiate an initial essay in humans at the end of 2024, so there are still a few years to know the answers.
What if we avoid injection?
Meanwhile, there is already an alternative way to administer semaglutida: in the form of a pill.Novo Nordisk, which manufactures Ozempic and Wegovy, also manufactures Rybelsus, a tablet used in the treatment of diabetes, and is now testing a higher dose version for weight control.Its competitor, Pfizer, is developing its own pill, which also imitates the LPG-1.Tablets can help follow a dosing regime because they are more comfortable than injections, but also entail the risk of gastrointestinal side effects and should be taken repeatedly.
It is still unknown if Fractyl gene therapy will cause similar side effects.With Ozempic and Wegovy, these effects usually appear in the early phases of the drug taking, when the dose is increased constantly.Normally, they disappear for themselves.
"The effect that the medication causes nausea actually occurs in the brain," says Randy Seleyy, professor of surgery and obesity specialist at the University of Michigan and whoHe is fractyl advisor.Since Fractyl gene therapy is administered in the pancreas, it can avoid the problem of side effects.But if part of the LPG-1 reaches the bloodstream, Seleyo warns that side effects similar to those of current drugs could occur.
However, if single -shot gene therapy works and is safe, it could change the rules of the game in the control of diabetes and overweight: "Type 2 diabetes is a chronic disease that should be treated chronically. Obesity isA chronic disease that needs chronic treatment, "Seley warns."If you just have to give access to people once, instead of each week, the use of this strategy will increase and benefit more patients."
