“Rare diseases should be treated for free; if we do, we will understand the rest”

During the 1970s, when Jude Samulski (North Augusta, USA, 1954) was a young researcher at Princeton University (USA), there was great interest in the role of viruses in the appearance of tumors.

On a trip to the United Kingdom for a meeting on the relationship between viruses and cancer, he stayed in a humble boarding house run by a woman with a son with muscular dystrophy, a disease that causes progressive muscle loss.

Samulski asked her what the doctors were doing to treat the boy, who was less and less mobile, and she answered something that left him cold: “Move the bed from the top floor to the bottom floor, because soon he will not be able to climb the stairs. ”.

“I kept thinking that this was not medicine, that nothing was being treated, and I realized the impact that our work could have if it were successful”,

40 years ago, this professor at the University of North Carolina (USA) became one of the pioneers of what is now known as gene therapy.

The idea was to take advantage of the ability of viruses to infect human cells and use them as a means of transport to introduce genetic modifications and cure diseases such as muscular dystrophy.

The American researcher identified a type of virus, the adeno-associated virus (AVV), which was less likely to cause disease and could be safer, and the promise of a cure for many diseases seemed close.

However, in 1999, a young man named Jesse Gelsinger died from an inflammatory response to an adenovirus that was supposed to introduce a gene into his body to repair a defective one that caused a metabolic disease.

Yet, as has been the case with such therapies from the beginning, parents of sick children with no hope other than science continued to goad stubborn researchers like Samulski.

When industry money ran short, patient family-funded foundations kept the flame alive, and two decades after Gelsinger's tragic death there is an explosion of trials, with more than 5,000 registered.

The US drug agency and the European Medicines Agency estimate that by 2025 they will approve between 10 and 20 cell and gene therapies each year.

People suffering from rare diseases, caused by the malfunction of a single gene, will be the first to benefit, but if there are no more major setbacks (there have been deaths in recent clinical trials,

Samulski recently visited Madrid because since 2017 he has business ties with Spain.

He founded Asklepios (known as Askbio) in 2001 and developed the technology that has enabled the therapeutic use of gene therapy.

The production of viral vectors is a key component of the technology, and in 2017 he decides that it should take place in Spain (San Sebastián) with a

(Viralgen) with Columbus Venture Partners.

In 2020, the multinational Bayer acquired AskBio for 2,000 million dollars, and the possibility of 2,000 more linked to certain milestones.

Samulski came into contact with Javier García Cogorro (founder and president of Columbus, and now also CEO of Viralgen) in 2014. This relationship leads to the creation of Viralgen.

This San Sebastián-based company, to which AskBio has assigned the rights to its technology, is dedicated to the production of these vectors, a fundamental tool for those who carry out tests or treatments with gene therapies.

Bayer, which also bought Viralgen in 2020, has invested 80 million euros in its San Sebastian factory to make it one of the providers of viral vectors for the entire world.

“It's a progression: first you died early, then a bypass, then a pill for the rest of your life, then gene therapy to fix it.

And almost all diseases can follow that path”

Ask.

When you began to investigate viruses to introduce this type of therapy into the body, did you do it out of purely scientific interest or were you already thinking about its applications?

Response.

I am a child of the 60s, of

.

It was about going with ambition where no one had gone before.

We believed we could do anything.

When I went to university, we knew the concept of recombinant DNA: take, for example, the insulin gene, put it in a bacterium and make the bacteria make insulin instead of extracting it from animals, as was done until then.

I was fascinated by viruses, which were like molecular delivery trucks to carry a genetic payload wherever we wanted.

I was very young and my thesis professor was only five years older than me, so we had a huge curiosity, which was probably our driving force.

And it was a time when you could do anything thanks to this new technology to cut DNA and put it from humans into bacteria or into viruses.

For the first time in history we were crossing different species at the molecular level and it was fascinating from a disease point of view.

But I didn't have a specific interest in diseases, it was something more related to adventure, with the possibility of doing something like going to the Moon.

Although when we made the viral vectors, we soon saw their possibilities against hemophilia or cystic fibrosis.

P.

After Gelsinger's death, in which the investigation was slowed down, now everything is going much faster and there is much more money, but there are still problems, trials are still being stopped due to some deaths.

R.

It is a process that is common in new technologies, there are advances and setbacks to later advance again, the same with computers as with organ transplants.

With transplants, at first, a patient could live for a month and there were many rejections, but then it got better and now people receive transplants all over the world.

We are on the same kind of roller coaster.

We have to have the persistence and tolerance to get through these storms that may come.

Q.

Now gene therapies are more promising for rare diseases that are caused by the failure of a single gene.

Will they be able to be effective against more complex diseases in the future?

R.

I defend that rare diseases should be treated for free, because with what we learn from them we will treat the rest of the world with complex diseases.

Imagine if I could take a viral vector, put a gene in it and put it in your liver so it makes a protein, and the protein circulates and is used to treat hemophilia and it doesn't bleed.

Along the way, we have learned something fundamental about putting something in an organ and the organ producing the protein.

Now, think you have 10,000 people with cancer and we have a monoclonal antibody that we can give them every two weeks to treat it.

But if I put the gene for that monoclonal antibody into a vector and I put it in his liver and the liver pumps out that protein the same way it pumps out the hemophilia protein, I have 10,000 people who don't have to take that monoclonal antibody anymore. .

With rare diseases we are answering fundamental questions that will have application in much broader populations.

You can imagine it for Alzheimer's or Parkinson's, cholesterol or diabetes.

They are all complex diseases that can begin to be regulated because we know the responsible genes, we just don't know how to regulate them or bring something specifically there.

It will permeate the entire medical field.

We are a body of genes and by managing these diseases we are learning how to turn genes on and off.

P.

Do you think that these therapies will arrive safely or may there be new inconveniences that will make them never come true?

R.

I bet you what you want.

If we don't have wars between countries or pandemics and we work for the common interest, it will happen much faster.

Forty years is a long time, but muscular dystrophy had been known for a hundred years and nothing could be done until a century later.

Now the technology is advancing faster and faster.

I am optimistic and I think that in the next 10 or 20 years we will see new drugs for genes of complex diseases that until now seem impossible to treat with these therapies.

Q.

If we push the possibilities of gene therapy to their limits and modify all human beings to have what we consider to be a perfect life, won't it all get a bit monotonous?

R.

We all came from a mother who left Africa and look at all the diversity that exists.

I think there will always be diversity, and that diversity is what gives us Einstein or phenomenal musicians, and it also gives us horrible diseases.

But it's not just genes.

It is the environment that makes you end up becoming who you are.

You, born today, are different from what you would be if you were born 100 years from now.

I think we put too much emphasis on the gene as the ultimate.

It is only the first step in the story.

“For the first time in history we were crossing different species at the molecular level and it was fascinating from the point of view of diseases”

P.

At the moment, gene therapies are very expensive [many in the order of hundreds of thousands of euros].

Do you think that the cost will be a limitation for them to reach the general public?

A.

Right now, the technology is very expensive because it takes a lot of labor and a lot of resources to make a single vector to treat a patient, but that will get better.

It's like the phone industry or the car industry.

Demand makes production more efficient and prices fall to make it available to more people.

But we are at the beginning and let's say that you have to pay for 40 years of research.

In addition, people with rare diseases will be given the opportunity to participate in society, to work, to pay taxes.

For a long time, all these people have been able to do is adapt while the disease worsens.

The way of treating diseases is going to change and that also has an economic impact.

My father has high cholesterol and all of his brothers died in their 60s from hardening of the arteries.

He was the only one who received a

and lived seven to ten years longer than his brothers.

I take a cholesterol pill and all my brothers too, and we are older than them when they died.

I have the opportunity to take something that they did not have.

If we develop a gene therapy to regulate cholesterol, it will be a unique treatment compared to our daily pill.

It's a progression: first you died early, then a

, then a pill for the rest of your life, then gene therapy to fix it.

And almost all diseases can follow that path.

Q.

Patients and their families have been a great impetus for this field.

Is there a case that has marked you especially?

A.

There is a boy named Connor.

He was the first patient in the muscular dystrophy trials and his parents have twins.

One has the disease and the other does not.

If we look at a photo of the two of them, one is normal height and the other is shorter.

So every day, parents saw one child grow up and the other not.

It was a constant reminder and it's very hard.

So they had to make a decision to buy him a new wheelchair or try gene therapy, which is like being the first to jump off a mountain or doing something terrifying.

We became very close.

They write to me all the time, they send me photos, they visit me.

It's like I've adopted this person into my life.

So when I talk to my students, who have very hard jobs and are facing very difficult problems to solve, I tell them: you need a Connor.

When you have it, you commit and get the job done.

I have two children and two grandchildren, but the relationship with Connor is very different, because we are in the same experiment together and we need to make it work.

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