Disclosure: Jennifer Graves, MD, PhD, MAS, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: TG Therapeutics
Received income in an amount equal to or greater than $250 from: TG Therapeutics
Thank you for the opportunity to join you all today to talk about what I think is one of the most critical topics facing people living with multiple sclerosis (MS) and taking care of people with MS, and that is the topic of aging.
My name is Dr Jennifer Graves. I'm professor and vice chair of neurosciences at the University of California, San Diego, and I have the opportunity to take care of people living with MS across the lifespan, from pediatric MS to those aging with MS.
There are three things I'd like to discuss with you today. First, we know from recent data that in the United States, over half of the individuals living with MS will be living with it over the age of 50. This highlights the importance of understanding how aging impacts those with MS.
The second thing I'd like to discuss with you is how age is the most important factor that drives how disease is expressed in those living with MS. This impacts how we take care of people living with the disease in terms of how we offer treatments, how we monitor them for safety, and how we try to advocate for them to live their best possible lives with this disease. Lastly, I'd like to talk to you about this concept of senotherapeutics and how we could target aging for better outcomes in MS.
Coming back to the first topic, Dr Wallin and colleagues published, about 5 years ago, in 2019, new data showing the incidence and prevalence of MS in the modern era. In these data, we see the consequence of not only better treatment for people with MS, but also better healthcare overall. We see that over half of individuals living with MS will be doing so over the age of 50.
This is very important for all healthcare providers to realize because it is part of our job to help them age well living with this disease. This is very important to us also because those who are older with MS tend to have a progressive form of the disease, and this shifts how we think about providing medications and supporting them.
This brings me to the second point that I wanted to emphasize today, which is that age, including your birth date age, your chronological age, as well as biological age, are the strongest factors that determine how MS is expressed in any one individual.
Let's start with one age extreme, pediatric-onset MS, which occurs in about 5% of patients living with MS. These kids can have onset as young as 3 to 4 to 5 years old, although most of them present around the time of puberty. They have three to five times higher relapse rates than adults living with MS. They have very inflammatory disease, and while years ago we thought we should treat them gingerly with lower-efficacy medications, we've come to appreciate that they need the most aggressive treatments to prevent relapses and to protect their brains for living with this disease for 60-80 years.
Compare this with older individuals living with MS. They have, roughly, a 10- to 20-fold lower relapse rate than these children. People over 50 or 60 years old may have a risk of relapsing only once per 10 years compared with twice per year in children living with MS. This means that, in these older individuals, it may be less appropriate to be aggressive with immunosuppressive therapies. Their risk for infections is increased at these older ages, and we need to think about treating them differently.
Those living in between -- in their twenties, thirties, and forties -- with MS have an intermediate level of relapse rate, approximately once every 2 years. They have some inflammatory disease, and beginning in their forties they become at risk for the progressive forms of MS.
Age is one of the most important factors in thinking about someone's risk for relapse, the appropriateness of placing them on immunosuppressants, and the risk for progressive MS. Children don't get progressive MS and we know that birth date age as well as biological age factors, such as telomere length, epigenetic age, and other markers of the biological aging processes, predict having more of a progressive phenotype with accumulation of physical and cognitive disability independent of relapses.
This brings us to our final and important topic of how to best help people aging with MS. One point is to understand this connection between biological age and chronological age and the accumulation of disability. What are the underlying biological processes behind developing progressive MS? When we understand that, we may become closer to finding a cure for these largely untreatable forms of MS, primary and secondary progressive MS.
To address this, we not only need to study our currently available treatments for MS for their potential to work in the aging population, but we may need to develop a new class of therapies that are directed at an aging immune system and an aging central nervous system.
This field outside of the world of MS is called senotherapeutics, or therapeutics designed to target aging cells or senescent cells either by modulating their behavior or eliminating them if they are causing toxicity to the human body and worsening disease.
What's really exciting is that, outside the world of MS, there's progress in these therapeutics, and we're beginning to see interest in applying them in people living with MS. These include repurposing of medications that are already used in multiple medical contexts. Drugs such as metformin, which is used in diabetes, are now being studied in multiple clinical trials in MS to see if this reversal of aging processes could cause benefit in people living with MS.
While we develop these senotherapeutics and we begin to think about an aging immune system and what types of drugs would target this best without causing harm to patients, we can employ and implement things that we already know impact the biological aging process and may cause benefit in those aging with MS.
This includes lifestyle factors like having a healthy diet, whether it's Mediterranean plant-forward diets, possibly even intermittent fasting, all of which can reverse biological aging and perhaps cause benefit to those living with MS, and also physical activity. We have numerous studies showing the benefits of continued physical activity, even in the face of accumulating disability in people with MS.
As people age with MS, we need to look for ways to keep them physically active and actively engaged in rehabilitation strategies. There can be many barriers to this, including funding, insurance coverage, or our own perceptions of what an accomplishment is for someone already facing lower-extremity disability with this disease and [trying to maintain] physical activity.
Ways to overcome these barriers include working with physical therapists, rehabilitation experts, as well as looking at mobility devices, such as arm bikes for cardiovascular activity, recumbent bikes, and ways to keep our patients active. This is not only going to benefit their function but it may actually reverse some of these biological aging processes.
In summary, what I'd like you to understand about people aging with MS is that this is not a rare problem. Thanks to improvements in MS care and improvements in our overall healthcare system, over half of individuals living with MS will be aging with it, and it will take all specialists working together to improve outcomes for these people.
Age is the strongest factor determining one's risk of having a relapse vs having a progressive form of disease and their overall disability expression. This means it's very important for us to try to keep our patients as young and healthy as possible despite whatever their birth date is and how many birthday cakes they've accumulated over their life so far.
It's important for us to think about the risks and benefits of immune suppression for individuals as they're aging with MS, and whether, if their chance of relapse is low, you're doing more harm than good with immunosuppression. We need to develop new medications that target the aging immune system specifically without increasing risk to patients.
We need to more universally deploy things that we know work in reversing biological age and supporting aging populations, including diet, exercise, rehabilitation, and continuing to keep our patients cardiovascularly active, even as they accumulate lower-extremity disability. These are critical concepts, and I think targeting these concepts and targeting aging ultimately will allow us to find a true cure for people living and aging with MS.
Thank you so much for joining us in this important conversation today.