Secrets of an almost human cell factory that hopes to cure Parkinson's

Medical science is going through a moment of reflection. There are laboratories that have been very successful in the production of medicines and that have now added a new direction, enrolled in the demand to eradicate incurable diseases such as Parkinson's, cancer or blindness. How? No medications.

This is cell therapy, which consists of reprogramming adult cells, "erasing their memory" and respecializing them for a different function. That is, to allocate them to a tissue of the body that needs to be repaired. They are, for now, treatments and promises of very expensive treatments that generate illusion and bring the issue of access back to the center of the scene.

Clarín traveled to Boston, in the United States, to learn the secrets of BlueRock Therapeutics, one of the most advanced cell factories in the world. It was bought in its entirety, in 2019, by the pharmaceutical company Bayer (which had founded it in 2016 in partnership with Versant Ventures). The goal is ambitious: to be the largest cell therapy company on the planet.

Seth Ettenberg is the president and CEO of BlueRock. In a press conference with Latin American media, he referred to the state of development of the projects in which they work, focused on four types of disorders: Parkinson's, heart damage, cancer and ophthalmology.

"We can build any cell and any gene," says Ettenberg in a building in Cambridge, very close to Harvard University and the Massachusetts Institute of Technology (MIT). There is the laboratory in which researchers try to find the best formula to develop each type of cell. "Each of these cell types is a beautiful masterpiece in itself when trying to create it," enthuses the project leader.

Seth Ettenberg, CEO of BlueRock Therapeutics: "We can build any cell and any gene."

Ettenberg makes during a presentation with filminas two clarifications that bring mystery and fascination to the subject. He says the brain cells they produce, dubbed Bemdinapra, aren't quite human: "We can make a cell that looks a lot like a human cell, but we're not there yet in terms of creating a 100 percent human cell."

Then he warns that he prefers not to speak of "cure", but of tissue regeneration, although for the imaginary the cure would probably be the happy result of a successful regeneration. With semantic and scientific caution, the biologist tries to surf ethical debates and excessive expectations.

How to get cells

How do BlueRock get the cells they then work with? "We work with so-called induced pluripotent stem cells, which means that from a healthy donor we take a blood sample and then reprogram that cell," explains Ettenberg. That procedure earned the Nobel Prize in 2012 to Japanese researcher Shinya Yamanaka.

From that possibility, what BlueRock does is use a patented bioprocess and manufacturing techniques to create stable master cell banks, capable of virtually unlimited expansion and differentiation in any type of cell.

"We can make exactly the same batch of cells over and over again," Ettenberg agrees. But for that to happen there must first be the first step, that of creation. That is, to obtain a specialized cell from something that is only a "blank sheet".

Clarín was able to witness the result of this scientific "miracle", with the case of generic cells transformed into cardiac cells. They were displayed during the visit to the laboratory on a screen through a microscope. You could see the heartbeat of the cell proper to its specificity, to the surprise of those present.

In the case of the heart, it is a preclinical study that seeks to advance towards a first clinical phase, although there is still no certain date for it. The same goes for immune cells and those thought to replace damaged eye cells resulting from macular degeneration or inherited retinal disease.

What is more advanced is the trial against Parkinson's, whose first results generate illusion. The optimism in BlueRock seems to indicate that phase 1 has been encouraging, although the small size of the sample – only 12 patients – leads Ettenberg and his collaborators to be very careful. The data will be known during the second half of 2023.

"There has been no news against Parkinson's for 60 years," says Ettenberg, with the confidence of someone who seems to be in a position to announce "the novelty". The drugs used today, he explains, have a decreasing performance to combat this disorder of the central nervous system that affects movement and usually causes tremors. "I'm excited about the results, but we have to be responsible," he said. Then comes phase 2.

There are several laboratories that advance in cell therapy projects, but in BlueRock they believe that they have a powerful weapon to stand out from the rest: the possibility of producing the cells obtained on a large scale, so that in terms of market and need they work like any other drug.

"As elegant and beautiful as it is, technically it's very bold to try this. No one has done it before and you can only imagine what it's like to deliver cells to the right place, have them graft into the body, integrate and become part of that neural network," Ettenberg says.

Bing in action, demonstrating his work in the lab.

A key link in that virtuous chain is the key so that those implanted cells, in order to repair damaged tissues, are not rejected by the person who receives them. That's what David Bing, one of the company's 400 employees, works on, whose responsibility is key: gene editing. That is, cut and paste genes in order to achieve the exact combination that leaves it free of rejection. It would be useless to obtain healthy brain cells to be implanted if the body does not assimilate them.

The problem of access

One thing is the developments in advanced health and another, the possibilities of access so that these advances effectively reach patients. How can we ensure that these new ways of dealing with diseases, never before imagined, do not get bogged down in scientific gloating or remain only within the reach of a few?

Adib Jacob, president of Bayer's Pharmaceutical Division for Brazil and Latin America, sees it this way: "If we reach a cure for Parkinson's we will greatly reduce the cost of the system, medical consultations, the hospitalization of young people who have to stop working. That person is going to be returned to society. Therefore, the new paradigm imposes having a view that is more about the cost of treatment and not the cost of therapy."

What's the difference? Jacob explains that "payers must be sensitized to the cost of the cell or gene therapy system. Cure, once. Second, there has to be funding. For example, paying for months or years. And third, risk sharing models. This means that if the product doesn't work, you don't have to pay." A model that already applies in some countries.

Good news for Argentina is that it is the first country in Latin America to create a specific regulatory framework for this type of new therapy. This would mean that the country can be better prepared to move forward with the eventual adoption of these advances when they become available.

Boston. Special Envoy

PS