Gene therapy explained (by Dr Ignacio Blanco) Part One

00:00:18: Hello everybody and welcome back to the second episode of The NF Podcast.

00:00:23: I'm Klaas Röhl, founder of NF Patients United and head of the Austrian Patient Organization NF Kinder.

00:00:43: NF patients united to bring all European patient organizations together.

00:00:49: In our first episode we sat down with Matt Bolts Johnson from Urodis, to talk about his important work in mental health.

00:00:57: a really insightful conversation.

00:00:59: today We're excited to welcome another specialist Professor Ignacio Blanco A clinical geneticist From Spain who will share His expertise With us.

00:01:10: welcoming Ignacio

00:01:11: Hi, hello.

00:01:13: Thanks for inviting me to have this conversation.

00:01:16: thanks.

00:01:16: It's always a pleasure to talk to you.

00:01:20: Ignacio, You work as the clinical geneticist in Germantria Hospital in Barcelona.

00:01:26: You completed your residency in general and digestive surgery at the Saint-Pau Hospital, Barcelona.

00:01:32: And you completed a research fellowship in medical oncology and immunotherapy at the University of Nebraska Medical School In The U.S.. Your board certified in general end digestive surgery and are accredited in the human genetics by The Spanish Society of Human Genetics.

00:01:52: So you're both a surgeon, and a geneticist?

00:01:55: Yes!

00:01:56: That's rare combination.

00:01:58: how did you find your passion?

00:02:01: Ah... You know when do start thinking.

00:02:05: why decide things in life?

00:02:08: this is always difficult.

00:02:10: When I was at medical school i was very anxious to answer to all the questions that any patient can give me.

00:02:21: The first time I thought surgery would be best way.

00:02:24: address these problems because you go right away, cure your patients and thats it!

00:02:32: When i finished my residency i moved to United States as u said to learn more about why patients have diseases.

00:02:45: to be in the United States with an important person for me, that was Dr.

00:02:51: Henry Lynch.

00:02:52: He discovered the Lynch syndrome and at that moment he started hereditary procreative cancer And I found him here so happy!

00:03:07: I was so amazed about genetics.

00:03:14: talking with patients, you can help them.

00:03:17: You don't need to operate then...you have to be there and I learn a lot from him.

00:03:24: And when i come back to Spain I decide to dedicate genetics.

00:03:31: The first years was a mixture.

00:03:33: it was practice surgery at the same time trying to introduce genetics in Spain In the nineties or two thousand and at the end I decided to move totally into genetics, more to rare diseases.

00:03:50: And a mix...and i was happy to find other guys here in Spain like Conchilazaro Educerra.

00:03:59: they introduced me on the wall of neurofibromatosis.

00:04:04: that way

00:04:07: remember my very first European NF meeting I went to.

00:04:11: it was here in Barcelona.

00:04:12: It was when i first met you, what makes genetics so fascinating?

00:04:20: Genetics is your new knowledge and science.

00:04:27: there are a lot of things that can improve learning at the same time.

00:04:38: Twenty years ago, there was no possibilities to perform genetic tests.

00:04:44: Right now we're performing genetics test and I'm sure that in a few years We will learn a lot more.

00:04:51: it means is you have A Lot of space To improve and to learn to study And this so challenging.

00:05:01: every day You have two to be studying with.

00:05:04: Genetics says.

00:05:05: he's passionate for me.

00:05:07: Yes, doctor.

00:05:09: And you mentioned that genetic testing is now so very much available in routine care as well and this really changed how you could identify carriers of a genetic tumor predisposition syndromes like NF correct?

00:05:25: Mm-hmm yes we have this opportunity now but we have A lot more to do because right now when I met the patient with NF I can make a genetic test and to find the pathogenic-genetic variant responsible for the disease but i'm not able explain what will happen.

00:05:51: in few years.

00:05:56: In next year we'll learn more about modifiers, modifier genes that allow us to make a better prognosis of the patients.

00:06:09: And this is what I am so excited about genetics, because every day it's different from other one and you can find different ways... ...to treat and manage patients.

00:06:23: that's an amazing world!

00:06:27: NF, of course is also a genetic disease.

00:06:30: Let's maybe look a little bit into the history of NF.

00:06:33: when was NF first discovered and by whom?

00:06:37: Okay there... There is some debate in the literature.

00:06:42: everyone recognized now that Dr.

00:06:45: Bohnrichenhausen was the first one who wrote The History Of Two Patients With NF.

00:06:52: but some other professionals doctors talk about neurofibromatosis just before him.

00:07:02: However, von Rieckehausen is the first one that writes about neuro fibromatoses in eighteen eighty-two.

00:07:13: yesterday however I don't know if you read it on a science paper someone has found possible Primary years, there were already patients with NF.

00:07:29: The plan is that the doctor was not able to recognize the disease but the disease has been with us forever.

00:07:38: Now we know, von Briekenhausen's was able to describe two families Patients and start their history.

00:07:49: since then many other small uh, achievement has been in the way improving what we already know about neurofibromatosis.

00:08:04: That is true.

00:08:04: there's.

00:08:04: um still it is a very unpredictable disease with large variation of symptoms sometimes even within the family that a parent can have a very mild case while the child will do exact same mutation might have modifying genes, what are the explanations for this large variability in NF-one?

00:08:29: We're trying to find explanation.

00:08:32: we don't have a total clue of that but I'm sure my opinion there has to be gym modifiers and environmental modifiers both things.

00:08:46: patients who were born with pathogenic genetic variant in NF-I have the risk to develop different symptoms but that patient has more than two thousand genes, they can modify.

00:09:02: The way that the pathogenic variant is acting and also the patients are surrounded by an environmental system diet ,the ways he teaches how is his race, whatever.

00:09:21: That can make an explanation of these changes this variability because as you say there are not two patients that are equal.

00:09:34: every single patient is different.

00:09:37: You mentioned genetic testing has become more and more important.

00:09:43: A good sign how important genetic testing is nowadays, that it was also added to the diagnostic criteria of NF-one in recent years.

00:09:51: Why's it so important to diagnose patients as early as possible?

00:09:57: This has been a huge debate here for example in Spain because if you diagnose your patient with NF one three four years earlier there is no real change.

00:10:16: However, we have to be in the place of a parent that has a child with six seven cafe only spots nothing else and We as a doctor ten years ago fifteen years ago.

00:10:33: We say okay?

00:10:34: We have to wait until eight years And if nothing else happens your child will be ok.

00:10:41: If something else happened The child would have NF one.

00:10:46: then We have to help families To know what is happening with her child.

00:11:00: For me, this one of the good reasons for introducing genetic tests in early stages.

00:11:09: If we perform a genetic test earlier, we can help parents to copy with diagnosis.

00:11:19: we will be able to say the parents yes, your child has an NF-one.

00:11:27: We won't be able this wars or less wars but we'll prepare a preventive plan and perform a surveillance program that help us identify different problems as soon possible the impact of these new manifestations.

00:11:56: That is very important, what you just mentioned to start following up with a patient and performing routine tests like example oftalmologic assessments because we now know that every fifth child develops optic pathway gliomas between the age.

00:12:15: So if we wouldn't be able to have genetic testing, usually children I would say twenty years ago were probably diagnosed not within the first three years of their life but probably when there are two or more other diagnostic features besides the calfalis.

00:12:32: But so maybe already during the critical age of optic pathway omens?

00:12:37: Yes you're right that's the opportunity!

00:12:40: We can start a real preventive program as early as possible.

00:12:46: That's important!

00:12:48: However, someone can tell you that okay... You're right one of every five trials with develop a glioma but probably if your are good doctor then know about NF-one and you will be able to identify these patients early enough.

00:13:08: I would say we have to standardize the way in which we deal and having the genetic test as soon as possible help us to identify patient health risk, make clear decisions about what to do.

00:13:25: Since NF is a genetic disease and all of these symptoms manifest because of the genetic variation gene therapy is future or big hope for many NF patients that will be a cure one day, because at the moment doctors are treating symptoms but not root cause.

00:13:47: How do you think will future of NF treatments look like?

00:13:53: As you can imagine as surgeon when I decide to deal with genetics i say okay... ...I'll operate genes and not patients to have all knowledge about genetic therapy in these years.

00:14:17: Everyone thinks that a genetic disease should be cured by gene therapy, but this is not easy and it's probably possible for everyone.

00:14:28: when I start dealing with genetic diseases i was very happy Down to the hill because I say okay, this doesn't work right now.

00:14:44: We have new knowledge that is increasing The possibility of a gene therapy.

00:14:53: we know Have tools To modify genes?

00:14:58: We have Tools to send genetic information to the cells to improve the production of proteins and we are hopping with this gene therapy.

00:15:15: I also want you be clear, The moment where we have to perform the Gene Therapy is critical.

00:15:24: if We're dealing With a patient that has already many manifestations It will Be difficult To remove all these manifestation That Has Been Down.

00:15:37: Probably gene therapy will be efficient for some manifestations or more efficient if we treat patients very early in life.

00:15:54: Gene therapy is a dream, I think that it's hope not hype but... We have to learn a lot still in order to-to be in place.

00:16:09: on the trip

00:16:11: I learned that the NF-one gene is the second largest gene in a human body.

00:16:17: So does this make it also more challenging to correct the gene, which is that big?

00:16:25: Yes you're right!

00:16:26: This one of the biggest ones and... It's difficult to correct but now we have other ways To overcome the problem that the gene has.

00:16:38: Right Now for example We can modify the area of the gene that is read.

00:16:44: This means you don't need to correct the exact point and also, You can introduce a complete error that allows cells to produce neurofibromine.

00:16:59: They are different ways.

00:17:01: To me more important problem is we have to treat all cells in our body.

00:17:09: That's very, very difficult.

00:17:12: It is not like for example in erratary diseases of the eye where you only need to treat retina In NF-I patients.

00:17:27: You should treat all cells on your body and modify them or be sure that you will introduce neurofibromine.

00:17:39: It's very challenging.

00:17:41: I imagine that must be a very challenging, tricky... Some gene therapy approaches use viruses to carry the gene therapy drug into different cells but i learned it still doesn't read every part because of the blood brain barrier.

00:18:01: or what is explanation for this?

00:18:02: Yes!

00:18:03: Because its a virus.

00:18:04: The virus isn´t able go through the different barriers that we have when if a central nervous system has a barrier in order to avoid toxic products, To reach The brain and then the DNA the virus is too big but you Have to reach also all pretty fellow nerves.

00:18:31: That's very challenging.

00:18:32: You have to reach All this trauma in the gastrointestinal area.

00:18:38: It's difficult, I wouldn't say no but it is very difficult.

00:18:44: and also imagine a patient that has plexiform neurofibroma who already started to develop premalignal lesions like an anoop or malignant tumor.

00:19:01: these cells have acquired different genetic alterations.

00:19:08: You can modify the first one, but if some other alteration has been already acquired yeah... The treatment is not helpful.

00:19:20: for that.

00:19:22: we have to look for different ways To introduce gene therapy But it's not an easy

00:19:29: procedure.

00:19:30: So there still a need much more continuous research to be performed, hopefully also public funding.

00:19:37: To go into this area as about I think almost eighty percent of rare diseases have a genetic cause so any advancement in this area would benefit many different rare diseases right?

00:19:50: Exactly and also we have as society another challenge because as you say eighty per cent of the rare diseases are genetics But every patient has a different genetic value.

00:20:07: This means that you have to deal with the different treatment for each patients, You cannot find like an aspirin for all NF-one patients... ...you should perform a genetic therapy For each different patient and this is very expensive.

00:20:27: So this personalized medicine at its best?

00:20:30: Yes!

00:20:31: Ah, you introduce a new term that is personal medicine and any doctor will say oh my god I always do in personal medicine.

00:20:44: We... it's now very interesting area where we have to perform personal medicine but also precise medicine.

00:20:57: both the new doctors are dream with a precise medicine.

00:21:05: We will be able to treat every single patient, the same way and best treatment but you should not forget about personalized medicines.

00:21:19: You have to talk with patients so that they know everything.

00:21:24: You need to know how the patient is feeling with his disease being apparent of a patient with NF-one that every patient is different.

00:21:38: You can find patients with thousands of neurofibromas, but they're okay!

00:21:44: They have been able to cope with the disease.

00:21:47: and then you'll find a patient who has single neurofibroma.

00:21:50: when the patient is scared or... ...you need to talk about how the patient feels, how their family's feeling.

00:22:01: You will apply also this precise medicine.

00:22:06: Thank you so much Ignacio for talking to me today, it was super interesting and thank you all the contributions that you have made to NF patients and caregivers!

00:22:15: Thanks to you!

00:22:16: This

00:22:19: is part one of episode two of the NF podcast.

00:22:24: I hope you all enjoyed as we did.

00:22:26: Again, if you have any questions or feedback for Ignacio or me feel free to write us on a platform.

00:22:33: You can find our contact information in the show notes.

00:22:36: Thank you for listening and until next time where we will talk about genetic counseling And exciting research projects.

00:22:43: so tune-in and bye for now.