It has been two decades since the Human Genome Project successfully unlocked the road map of what makes us “us.” The sequencing of the human genome1, mapping the genes that make up a human, was a 13-year effort, and this breakthrough, coupled with tremendous advances in technology, has brought forth a new frontier in medicine. We can now pinpoint the genetic causes of diseases in ways that will not only help us find treatments—but lead us to potential cures.
Despite a growing understanding of genetics, there are many misunderstandings about genetic medicines and how they work. Andrew Adams, PhD, co-director of the Lilly Institute of Genetic Medicine and senior vice president of Genetic Medicines and Neurodegeneration Research explains some of the most common misconceptions, and why patients should be hopeful about the potential benefits these therapies can offer.
Did you know that genetic medicines have been widely researched for several decades?
Genetic medicines are often thought of as a new form of therapeutic. However, it has been over 50 years since the initial idea of using genetically engineered treatments took hold2 and over 30 years since the first clinical trials studying the use of gene therapies began3. In fact, since the early 1990s, more than 1,900 clinical trials have been conducted studying genetic causes of diseases. In this period, we have seen application of potential gene therapies in a wide range of diseases, including certain cancers, neurodegenerative diseases, metabolic and cardiovascular diseases3.
Dr. Adams: “For decades, scientists and researchers have been investigating the development and utilization of genetic medicines to treat diseases. With recent advancements in biotechnology and a deeper understanding of the human genome and its connection to disease, we as an industry have been able to make significant progress. In addition to a large number of potential therapeutics advancing in clinical development, there are several approved genetic medicines in use today.”
Did you know that genetic medicine doesn’t narrowly focus on making permanent changes to one’s DNA?
While some people think genetic medicines involve permanently altering a person’s DNA, this is only one way we can apply the technology. In reality, genetic medicines allow us to target specific processes that contribute to the underlying cause of diseases in diverse ways, which often doesn’t require permanent changes.
Dr. Adams: “Genetic medicines may provide substantial benefits for people suffering from diseases with a known genetic driver. This includes a number of rare diseases like sickle cell disease, hemophilia and certain types of amyotrophic lateral sclerosis (ALS), but also potentially for more common chronic diseases like Alzheimer’s disease.”
Did you know that, despite challenges, the potential benefits genetic medicines may provide are within reach?
The delivery of genetic medicines is difficult because we must ensure the therapy is delivered to the correct place (e.g., the liver), with the correct genetic code to only make the change we intend. It is these challenges of delivery and specificity that occupy much of our scientist’s time today.
Dr. Adams: “Obstacles are present in almost every class of drugs. Groundbreaking therapies that we accept as standard today were advanced only after perseverance through disappointments and challenges. Figuring out the best way to deliver genetic medicines to the patient is critical to the success of these treatments and is a significant problem today, however, it’s a problem which I feel we are on the precipice of cracking. With success in delivery, we will be one step closer to achieving the ultimate goal— generating transformational medicines for patients.
At Lilly, for example, we are studying a method of delivery for genetic medicine using nanocarriers. These are incredibly tiny delivery vehicles which, because of their small size, can take therapies to otherwise inaccessible places in the body. By using nanoparticles to deliver our treatments, it’s possible that we can enable the ability to dose a patient multiple times until a sufficient therapeutic threshold is reached and maintained —all while avoiding unwanted immune responses. In ALS, these delivery vehicles hold the promise to allow us to take many new kinds of medicines, such as gene therapies and genetic editors, to the neurons in the brain and spinal cord which drive the disease.
When we are able to successfully deliver therapies, we may be able to provide significant benefits to patients living with diseases that today lack sufficient standard of care. With nearly 6 in 10 adults in the United States living with at least one chronic disease4, the benefits these therapeutics may have on society could be significant—and I am hopeful for what genetic medicines may be able to bring to patients in the future.”
Learn more about our work to advance genetic medicines and hear about the hope for the possibilities to come in a video produced for us by BBC StoryWorks below.
The potential of genetic medicine
00:00-00:14
[Video opens with a far away and then close-up shot of Hugo using a brush on a smiling Leah’s eyebrows. The camera shows a close-up view of both of her hands laying on her thigh and cuts back to Hugo brushing her eyebrows]
Leah: How’s your morning?
Hugo: Monday. Joker. How’s your morning, how do you feel?
Leah: I’m good.
Hugo: You feel ready for this big interview?
Leah: I’m ready.
Hugo: You've gotten better.
00:14-00:22
[The video zooms out to show Leah sitting in a wheelchair next to Hugo. Video cuts to Hugo and Leah sitting in chairs while Leah is talking to the camera, and then the camera shows Leah in her wheelchair staring out a window]
Caption: Leah Stavenhagen, 29, ALS Patient and Advocate
Leah: I'm Leah. I'm 29. I was diagnosed with ALS in 2019 .
00:22-00:34
[Camera shows a close-up of Leah and Hugo holding hands with wedding rings on, and then zooms in on multiple photographs in a photo book of Leah and Hugo smiling on their wedding day. Video cuts to Hugo smiling at her while she is talking to the camera]
Hugo: I know that she has always wanted to be dancing at her wedding so she was a bit disappointed. It was still a very beautiful event.
Leah: Magical. A very special evening.
00:34-00:48
[Camera shows close-up and faraway shots of Leah and Hugo paging through their wedding photo album, and then video cuts to the couple sitting while Leah is talking to the camera. Camera shows a visual of a baseball bat and Yankees baseball shirt hanging in front of a window]
Leah: A lot of people know ALS as maybe Lou Gehrig's disease, because Lou Gehrig was a very famous baseball player who had it. I think it was in the 1930 s.
00:48-00:53
[Camera pans across the name Lou Gehrig embroidered in a navy and white baseball uniform, and then cuts to the couple sitting while Leah is talking to the camera]
Leah: And what’s pretty incredible is the life expectancy is still the same as when Lou Gehrig got the disease.
00:53-01:12
[Leah continues talking to the camera as the video cuts to visuals of Hugo helping her drink a glass of water, wheeling her out of a kitchen, and putting a shoe on one of Leah’s feet]
Leah: So ALS, or Amyotrophic Lateral Sclerosis, is a neurodegenerative disease that leads to the paralysis of muscles. And so it's different for every patient but eventually that person can no longer walk, talk, breathe on their own.
01:12-01:33
[Leah continues talking to the camera as the video shows multiple visuals of Hugo pushing Leah while she is in a wheelchair and putting on Leah’s shoes]
Leah: It's devastating because your hopes, your dreams, they disappear. You have to rethink about what you want for your life, what your future’s going to be like. That your future might be much, much shorter than you thought. So it’s a total shock for you and for those around you.
01:33-01:45
[Camera shows Hugo adjusting pillows behind her back on a couch, and then multiple close-up and faraway visuals of Leah and Hugo looking through their wedding photo album. Video cuts to Hugo talking to the camera]
Caption: Hugo Taubmann, Leah’s husband and carer
Hugo: I've been married to Leah for two years and one day. Yesterday was our anniversary and I've been trying to support her the best I could for the past three or four years that we have had to live with this disease.
01:45-02:06
[Leah is sitting and talking to the camera while the camera shows visuals of Leah and Hugo sitting at a table and talking]
Leah: There's a stereotype that it's more older men but in reality - 45% women, 55% men that have it. Of those patients, 90% are like me. We don't know what causes it. But 10% have a genetic mutation and so that provides actually a key to potential treatments.
02:06-02:21
[Video cuts to a shot of an outdoor area, the Cambridge city skyline, and then Andrew sitting in an office setting talking to the camera]
Caption: Nature’s Building Blocks
Caption: Cambridge, Massachusetts
Caption: Andrew Adams, SVP, Neurodegeneration Research, Co-Director, Lilly Institute for Genetic Medicines at Eli Lilly & Company
Andrew: I think people may not realize just how little we know about diseases like ALS, Alzheimer's disease, Huntington's disease, Parkinson's.
02:22-02:37
[Camera shows close-up and faraway visuals of Andrew wearing a white lab coat in a medical research facility looking at a machine, and then Andrew sitting and talking to the camera]
Andrew: But really there are still fundamental gaps in how we understand those diseases progress. I think a lot of us are here at the Institute because we have family members that have some of these diseases and we're passionate about it because we want to solve it for people we care about. But also for everybody else.
02:37-02:59
[Video shows a visual of Andrew walking through white lab room doors, and Andrew sitting and talking to the camera]
Andrew: For me, I have a number of family members with Alzheimer's disease and a number of friends with ALS. The Institute’s mission, especially as it relates to neurodegeneration, what we're looking for here is to make zero to one innovations. We don't want to do incremental things where we target symptoms. What we're looking to do here is make transformational medicines.
02:59-03:09
[Video shows visuals of lab workers in white coats looking at a lab device, and then Michelle sitting in an office setting and talking to the camera]
Caption: Michelle Lynn Hall, Associate VP, Genetic Medicine Research and Neurodegeneration at Eli Lilly & Company
Michelle: Genetic medicine is basically doing everything that a lot of the medicines have done for years, but very intentionally focusing on treating and curing diseases at their foundational and root level.
03:09-03:25
[Video cuts to graphic illustrations of a brain inside a body, brain cells, a DNA strand, and disease state cells]
Michelle: For certain patient populations who may have certain neurodegenerative diseases, let's say Alzheimer's, we can go and precisely map in their DNA what is causing that, and then what we can do is one of two things. We can either go and treat the downstream effects of that.
03:25-03:42
[Video shows graphic illustrations of a blue and red DNA strand being replaced with all blue DNA to look uniform, and then the video cuts to Michelle talking to the camera]
Michelle: So that's more of treating the symptoms, creating treatments. Or we can go upstream of that to the DNA itself where that mutation is and fundamentally go in and correct it, correct that mutation to reverse the root cause of the disease and the word that I'm using here intentionally is ‘cure’ that disease.
03:43-04:03
[Video cuts to multiple visuals in a lab setting of Andrew looking at a microscope, lab workers studying a lab device, and Andrew looking at DNA on a screen, and then Andrew sitting and talking to the camera]
Andrew: If you figure out which of those genes are important, then you can actually take some of these newer strategies that we have today, things like gene therapy that people have heard a lot about over the last couple decades, and you can put functioning copies of those genes potentially back in to cells in people's bodies, and have them make a functioning version of those genes.
04:03-04:22
[Camera shows visuals of Andrew as he walks through a lab, a close-up of a lab worker withdrawing liquid from a tube, and a lab worker putting red vials of liquid into a container. Video cuts to Andrew sitting and talking to the camera]
Andrew: And so what we're looking at is drugs where you go to the root cause of disease that let you do that – where I give you one shot and you don't worry about ever developing Alzheimer's disease, that would be pretty amazing, I think, and most of us, I think, would be extremely excited to to join clinical trials maybe or to take that medicine if it's approved.
04:22-04:49
[Camera shows multiple visuals of Michelle walking through a lab, Michelle studying machinery with a lab worker, a close-up of a lab worker putting vials into a machine, while Michelle continues sitting and talking to the camera]
Michelle: Developing the tools, developing the medicines to have immaculate precision and accuracy is the largest obstacle we're dealing with at the moment. Once we can actually get them into your body making sure that they are getting into the cells we need and actually acting at the genetic level to reverse the effects that we want them to reverse, that tells you precisely how hard it is. It has to be precise. It has to be accurate.
04:49-05:18
[Video cuts to Andrew sitting and talking to the camera, and then shows visuals of lab workers holding vials of liquid and Andrew walking through a lab]
Andrew: We’re sort of in the the renaissance of genetic medicine, and I do believe that genetic medicine will be the thing that changes the course of diseases, like ALS. What we make here is hope for people with neurodegenerative disease. If people are out there, they're dealing with things like this, they should know that there are a lot of really dedicated people at places like Lilly that are working incredibly hard on solving problems for them.
05:18-05:39
[Video shows a close-up of Hugo wheeling Leah in her wheelchair and then cuts to Hugo and Leah sitting while Leah is talking to the camera. The camera shows visuals of a flier that says Her ALS Story, a photograph of Leah with two other women, a woman wheeling another woman down a city street, and multiple clear glass award trophies for Her ALS Story]
Leah: I've started a group called Her ALS Story and it's a group that brings together women that were diagnosed under age 35 so that we can both have a network to lean into, and also advocate for better, more accessible treatment options together.
05:39-06:02
[Video shows close-up shots of Leah’s hands on her legs and Leah looking out a window, and then multiple photograph of Leah with a man at dinner, Hugo kissing Leah on a rooftop in front of a city skyline, Leah smiling on a boat appear on screen as Leah continues sitting and talking to the camera]
Leah: So I feel very fortunate because I have such a great support system because I'm able to continue spending my time doing things I love with people I love. I travel all the time. I still have a beautiful life. I'm very hopeful that promising treatments will come out soon so that I can continue to live.
06:04-06:09
[Video shows a black screen with white Lilly and BBC StoryWorks logos]
Caption: Presented by Lilly
Caption: Produced for Eli Lilly & Company for BBC StoryWorks Commercial Productions
- Nurk, S., Koren, S., Rhie, A., Rautiainen, M., Bzikadze, A. V., Mikheenko, A., Vollger, M. R., Altemose, N., Uralsky, L., Gershman, A., Aganezov, S., Hoyt, S. J., Diekhans, M., Logsdon, G. A., Alonge, M., Antonarakis, S. E., Borchers, M., Bouffard, G. G., Brooks, S. Y., … Phillippy, A. M. (2022). The complete sequence of a human genome. Science, 376(6588), 44–53. https://doi.org/10.1126/science.abj6987
- Friedmann, T., & Roblin, R. (1972). Gene Therapy for Human Genetic Disease? Science, 175(4025), 949–955. https://doi.org/10.1126/science.175.4025.949
- Tamura R, Toda M. Historic Overview of Genetic Engineering Technologies for Human Gene Therapy. Neurol Med Chir (Tokyo). 2020 Oct 15;60(10):483-491. Doi: 10.2176/nmc.ra.2020-0049. Epub 2020 Sep 8. PMID: 32908085; PMCID: PMC7555159.
- Chronic Diseases in America | CDC. (n.d.). https://www.cdc.gov/chronicdisease/resources/infographic/chronic-diseases.htm