NEW YORK.- Three years ago, a new and little-known federal agency announced its first major project: would invest tens of millions of dollars over five years to find a cure for osteoarthritisthe painful wear and tear of joints that affects 32 million Americans.

Now the agency HARP-H (Agency for Advanced Health Research Projects, for its acronym in English) states that has several promising solutions. Its research teams are contractually obligated to begin testing on patients within the next 18 months.

The new research concentrates on the knee osteoarthritisalthough researchers believe the solutions could, over time, be applied to any joint affected by the disease.

Two research teams, at Duke University and the University of Colorado, based in Boulder, developed injections or infusions that regenerate bone and cartilageas reported by ARPA-H this Monday. A third team, at Columbia University, might have found a way to regenerate a whole knee.

Until now, the methods were only tested on animals. Even so, specialists consulted said they were encouraged by the results.

“It is enormously promising,” said Dr. Scott Rodeo, vice president of orthopedic research at the Hospital for Special Surgery in New York, who was not involved in the studies. “Today everything we have is limited to modifying the symptoms,” he added. Curing arthritis by regenerating cartilage and bone “would be a paradigm shift.”

Finding a completely new approach is the goal, explained Dr. Ross Uhrich, ARPA-H osteoarthritis program manager. “If your goal is only to publish an article in a scientific journal, this is not the right agency,” held.

Arpa-h reports to the United States Department of Health and Human Services. Its operation is inspired by a similar program of the Department of Defense, Darpa (Defense Advanced Research Projects Agency), which contributed to the development of Internethe GPS and the autonomous dronesamong other technologies.

At ARPA-H, scientists who applied for funding to research arthritis—selected from companies, laboratories, and teams—agree to solve the problem in both preclinical and clinical studies. If the treatments are successful in humans, they must then advance in their commercialization.

Researchers must also accept that their treatments will be tested in the groups most likely to need them. This implies that more than half of clinical trial participants must be women and the trials must include Native Americans and Alaska Natives.

Furthermore, if a treatment is approved for marketing, cannot cost more than 25 percent of the price of the current standard of care.

The leaders of the Columbia University team, biomedical engineers Clark Hung and Nadeen Chahine, claim to have developed a way to regenerate a knee using an artificial joint made from a 3D printed biological scaffold, a biodegradable structure that supports the growth of bone and cartilage cells.

Those cells grow into healthy bone and cartilage, while the scaffold progressively dissolves over about a year. The treatment is designed for so-called “bone-on-bone” patients. who lost all or almost all of the cartilage in their knee.

The cells that fill the scaffold can come from the abdominal fat from the patient himself or from cells donated and preserved in banks. In the first case, researchers isolate stem cells and then use biological modifiers to guide them until they transform into bone and cartilage cells, a process that takes about a month.

Stored donated cells, on the other hand, do not need to be transformedexplained Dr. Chahine. In the experiments carried out by the team, these cells did not trigger an immunological reaction, despite their origin.

To test whether the scaffold would function like a real knee—capable of supporting weight and maintaining flexibility— The surgeons implanted the experimental knees in cadavers and used robotic systems to evaluate their fitness for walking..

The next step will be test the system in larger animals, Chahine noted. The five-year contract signed with ARPA-H gave the team a little more US$42 million. “In academic research, this is like money from the sky,” he said.

A typical federal grant It’s just over half a million dollars. But in that type of funding, researchers are not expected to take their work from theory to approval for commercialization.

At Duke University, Dr. Benjamin Alman, an orthopedic surgeon, explained that the team asked themselves a central question: whether it was possible to make a patient’s cartilage cells regenerate again.

In the most advanced stage of osteoarthritis, there are no cartilage cells left. However, the vast majority of people with the disease still have some in the knee. Could these cells begin to divide and repopulate the joint with healthy cartilage?

In osteoarthritis, the bone also becomes thicker, which alters the mechanics of the joint. Would it be possible to remodel it so that the knee can function normally again?

The researchers tested different medications, alone and in combination, and finally came up with three treatments. One consists of an injection that stimulates the growth of cartilage cells. Another remodels the bone. The third is an infusion capable of treating several arthritic joints at the same time and also promotes cartilage growth.

“The idea would be that, If the patient’s main problem is in the cartilage, let’s attack the cartilage. And if it’s mostly in the bone, let’s attack the bone,” Alman explained.

The treatments worked in rats and mice. “I’m usually very skeptical, but this surprised me,” he admitted.

For her part, Stephanie Bryant, a chemical and biological engineer and team leader at the University of Colorado, Boulder, explained that Their goal was to “return the tissue to a healthy state,” with a single injection at most.

The group identified a drug—a repurposed drug already on the market—that worked in animals, and developed a formulation that allows it to be released in pulses over several months. “The medication remains inside the joint long term”he pointed out.

The tests included rabbits that were given the equivalent of an anterior cruciate ligament tear in humans. As in people, animals quickly developed osteoarthritis. Two months after the injection, his knees had regenerated.

The other animal model was the guinea pig, which develops a type of degenerative arthritis similar to that which usually appears in people over time. One more time, The treatment was completely effective for the knees.

And what about people who already have advanced “bone-on-bone” arthritis? The Colorado team developed a mixture of engineered proteins that are injected into the joint and occupy the space where cartilage would normally be.

These proteins attract the so-called progenitor cells of the underlying bone and induce them to regenerate. In the rabbits in the study, It took just three months for the injected material to completely disappear. In its place, healthy cartilage was left.

The team, Bryant said, was ecstatic. “You do all this work, you have all these hypotheses, but you never know if it’s going to work,” said. “Very few of us have the opportunity to really push the developments we work on. This is a concrete opportunity to really help patients.”