Empowering the impatient patient revolution

February 28 is the Rare Disease Day, and the global theme this year is research.

People from all over the world will come together this month to advocate for more research on rare diseases, and to recognize the critical role that patient organizations play in research.

I don’t think the organization could have come up with a better theme. I’m a strong believer in patient-centric research. In working with patient organizations who are changing the world. This is why I am excited to join this year Rare Disease Day and announce the launch of my first eBook: #ImpatientRevolution, a guide for impatient patient organizations.

WHAT IS THE eBOOK ABOUT

This eBook is about the many ways patient organizations can shape the research field around their disease and influence the drug industry to work on their rare disease.

I conceived it as a guide for impatient patient organizations – those wanting to accelerate the development of new medicines for their disease by taking an active role. It explains why and how companies develop drugs for rare diseases, and how patient organizations can use this knowledge to analyze their disease field, to identify the main gaps, and to design strategies to get pharmaceutical companies to develop new treatments for their disease.

My wish is to empower patient organizations that want to play an active role in research, and to invite them to take the plunge and join the #ImpatientRevolution

WHAT IS THE AUDIENCE

As a guide, the eBook is written for patients and patient advocates involved in patient organizations. It will be very useful for those just starting or even considering starting a new patient organization, and it will be a good mental exercise too for those that are already part of patient organizations that are active in research.

As a learning resource, the eBook will be interesting for anyone involved in developing new medicines for rare diseases (orphan drugs), in particular if they interact with patients. I myself am a drug hunter, and this is the guide I would have loved to read when I started!

WHO IS THE AUTHOR

I have been a scientist in academia, a scientist in the pharmaceutical industry, and for the last 5 years I have worked as an in-house scientist and advisor for rare disease patient organizations.

While I looked for new ways to help develop more drugs for Dravet syndrome, I also looked at the industry best practices. From this experience I came up with the framework that is the backbone of the #ImpatientRevolution eBook. I have shared these ideas at rare disease conferences and it was time for me to write them down so that I could share them with all the rare disease community. There was not better time for doing this than joining this year Rare Disease Day.

WHEN IS THE eBOOK LAUNCH

The #ImpatientRevolution eBook will launch on February 21, exactly one week before the Rare Disease Day.

I have chosen this date to celebrate the Rare Disease Day, and, at the same time, give time for people to read the eBook so that they get to February 28 more convinced that ever that patient organizations should be at the center of research.

WHAT IS THE COST

You don’t have to pay anything or sign up to any e-mail list to get the eBook. If you want it, it’s yours. All I will ask you is that if you read it and you like it then help me spread the word so that more patient organizations (or families thinking about starting one) will get to read it too.

WHERE CAN I GET IT

The eBook will be available on-line through this website with no payments or sign up required. I will share the link in social media on February 21 so stay tuned!

In the mean time, help me create awareness and spread the word in social media sharing your support for patient organizations playing a central role in research under the theme #ImpatientRevolution

And if you want early access to a copy, just leave me a note in the comments!

Ana Mingorance, PhD

How close are we to creating transgenic people?

The journal Nature just released one of the most anticipated breaking news of the last few years: CRISPR gene editing has been tested in a person for the first time.

In my day-to-day work I interact with families that have a child with a genetic disease. These are diseases where the mutation is produced “de novo”, which means that it happened during the production of the baby. The family didn’t carry any mutation and most likely that child is the only one with that exact mutation, or one of a handful world-wide. 

As you can imagine, ever since scientists announced they had found a way to do copy-and-paste in DNA to introduce or to correct mutations I get one question a lot: how close are we to turn that discovery into a therapy for people with genetic diseases?

And despite the breaking news from Nature the answer is still “not that close”.

Let me elaborate on that.

Before being available as a treatment for people born with genetic mutations the CRISPR technology needs to go through roughly four steps:

1. Show that CRISPR can correct mutations in human cells in a test tube. This was the groundbreaking discovery that got us started in an amazing medical development explosion.

2. Show that these genetically-modified cells can be delivered to patients. This is more cell therapy than gene therapy and it is very useful on its own. Likely to be the first path forward for the CRISPR approach.

3. Show that we can actually correct mutation in patients using CRISP. Now we are talking about gene therapy, and for years this will have to be done in clinical trials under controlled conditions.

4. Finally, get approval for gene therapy using CRISPR technology so that we can fix patient’s mutations, effectively creating transgenic people.

What Nature announces is that scientists at Sichuan University have treated a patient with lung cancer with cells that had been reprogrammed using CRISPR before being delivered into the patient. This is step 2.

It had also been done before using other technologies that enable gene-editing, also in diseases where scientists first modify those cells outside the body and then deliver them to the patient, such as in cases of leukaemia or HIV. CRISPR is predicted to be the most powerful (and easy!) of these methods and is likely to be the one that will become a real treatment so reaching step 2 is great news.

At this second stage, these are all “ex vivo” approaches where the gene editing technology is applied to the cells that will be used to treat the patient, instead of using the technology directly in the patient.

The move towards step 3, editing the patient DNA, opens serious safety concerns:could the gene-editing enzymes cut and paste more letters in the DNA that they were intended to? Could they cause unwanted mutations? Because of that, it is likely to happen first in very localized indications such as tumours or retinal disease.

Moving from those localized diseases to more widespread ones will have the same challenges to reach the target organs that “traditional gene therapy” currently has. For the non-initiated, “traditional gene therapy” doesn’t change the patient DNA, instead it uses virus that have been stripped of the virus DNA to infect the patient and deliver a healthy version of the gene that the patients have mutated. At the end the patient has his own genes plus this new therapeutic gene. And that is not easy to do in hard-to-reach organs such as the brain!

Because delivering the CRISPR enzymes will also rely on viral vectors, even if CRISPR was proven today to be totally safe we wouldn’t know how to apply it to the brain tomorrow, since we still haven’t mastered that delivery aspect yet.

For any patient with a neurological condition caused by de novo mutations (so mutations unique to him/her) this is how the things to do list looks like before we can treat him:

1. CRISPR needs to be proven safe in small regions (step 3)

2. We need to find good viral vectors to deliver genes to the brain, which is larger than the eye or blood cells and happens to come inside of a hard box.

3. Those viral vectors also need to be safe.

4. CRISPR will be first used for genetic neurological diseases that are inherited, which means where the same mutation is found in many people.

5. And only after all that has happened we can think of using CRISPR therapy when the target mutation is unique for each patient, which introduces additional questions: can we get approval for the disease and just change the target sequence that the CRISPR uses? Will companies ever manufacture separate ones for individual patients?  etc

So for the patients I work with, who carry de novo mutations that cause neurological diseases, the answer to how close we are to use CRISPR as a therapy for people like them can only be “not that close”. These are probably the last diseases to benefit from the gene editing technology.

In the mean time we celebrate that we have reached step 2 with CRISPR, delivering edited cells to a patient, and keep our eyes on that next frontier: the in vivo experiment, the first patient that has his own DNA corrected using CRISPR in a clinical trial, the first transgenic people.

Let me know what you think about it in the comments.

Ana Mingorance PhD

Originally published in LinkedIn on November 16, 2016

Impatient patients

One day I sent an e-mail that changed my life. During my training as a scientist, I had learned how to study what goes wrong with the brain and to research how we could fix it. Then one day I sent an e-mail to a patient.

There are about 7,000 diseases that are considered rare because less than 1 in 2,000 people have it. It is not like diabetes, cancer, or Alzheimer’s disease, that we have all heard about. Most people have never heard about these rare diseases, and often not even physicians have heard about them.

Because they are not that common, it often takes many years to find the right diagnosis for these patients, with many left undiagnosed for the rest of their lives. And for the lucky ones that get the right diagnosis, the likelihood of having an approved medication for their disease is 1 in 20. Imagine a 1 in 20 chance of getting a medication for your cancer or your diabetes. A horrible thought, isn’t it? That is the scary world where 350 million people with rare diseases live every day.

But a revolution is changing the way we learn about and treat rare diseases, and it is driven not by progresses in medicine but in technology. Technology, powered by next generation sequencing and bioinformatics, is making the diagnosis of rare diseases much easier and faster. And technology, through the explosion of social media, is helping people with rare diseases and their families connect with other families. And that’s when magic happens.

Five years ago I read an article about a small group of parents that had created a patient organization to find a cure for their children, all diagnosed with a rare neurological condition. They didn’t know how, but they certainly knew what. Andthat is some times all you need to start.

Before finishing the article I sent them an e-mail. I knew about the brain, I knew about drug development, I knew languages and people, and I knew I wanted to help them. That e-mail changed my life. Working with patients changed my life, and not just in the way I now approach drug development and my career. It also changed the way I understand life. Because the only thing harder that being confronted with the reality that there is just a 1 in 20 chance of getting a medication for your disease is when the one with the disease is your child. And many have chosen to get together and do something about it.

That’s why I like to call them impatient patients.

The impatient revolution is already changing the way we do medicine. Patient organizations are becoming central members of the research community and key partners in the development of new treatments. The momentum the impatient patient movement has gained in some fields like rare diseases is unstoppable. And they are not doing it alone. Just like the social media that helped them get started, it is people connecting to people that fuels this movement. Impatient people willing to reach out to patients and their advocates and help create the connections and bridges that they need to succeed. Just like a LinkedIn network, every time we connect with a patient organization we expand their reach, and what starts as a rare disease of few individuals soon becomes a large network of 3rd degree connections that spans across industries and society.

And that’s when magic happens, and why I like to call them impatient patients.

Ana Mingorance PhD

Originally published in LinedIn, October 28 2016