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Over the past 25 years, significant innovation has advanced the treatment of multiple sclerosis  (MS), addressing the frequency of relapses for this chronic neurological disease. But on a daily basis, the 2.5 million people living with MS worldwide still face many challenges associated with their disease.

Hoping to help address these persistent challenges, Celgene has joined with the chronic disease-focused, patient-empowerment platform Lyfebulb to launch the Lyfebulb-Celgene 2019 “Addressing Unmet Needs in MS: An Innovation Challenge,” which will provide $25,000 to one patient entrepreneur who is developing solutions to address an unmet need in MS. The goal of the initiative is to seek new solutions, beyond therapy, to help address either challenges faced by people with MS in their daily lives or an unmet need that could potentially improve outcomes and experiences for both people with the disease and their support partners.

To introduce this innovation challenge, Lyfebulb and Celgene hosted an event on January 24 in New York. The event featured a diverse panel which included a neurologist, MS patient and patient advocacy leaders who gave their perspectives on the current challenges in MS care and the evolving needs of patients, caregivers and clinicians.

Supporting Patient Entrepreneurs

While most people may not be familiar with the concept of “patient entrepreneurs,” Lyfebulb is hoping that will soon change. When Lyfebulb was founded in 2014, its founders wanted to empower patients and those who support them to become active participants in the search for solutions to issues associated with chronic diseases like MS. Lyfebulb provides these patient entrepreneurs with opportunities to take part in summits and challenges – like the Lyfebulb-Celgene 2019 Addressing Unmet Needs in MS: An Innovation Challenge – to help themselves and others impacted by the disease.

These entrepreneurs not only have the drive to improve their lives and the lives of those who have experienced MS firsthand, but also have inside knowledge of the problems that patients with this chronic disease face. Or, as Elizabeth Jones, a patient and an advocate, put it, “No one understands what it’s like to have MS other than another person who has experience with it.”


KARIN HEHENBERGER, M.D., PH.D., MODERATED A PANEL FEATURING MS EXPERTS FROM ACROSS THE COUNTRY, INCLUDING A PERSON WITH MS, ADVOCATES AND A PHYSICIAN TO KICKOFF THE LYFEBULB-CELGENE 2019 “ADDRESSING UNMET NEEDS IN MS: AN INNOVATION CHALLENGE.”

 

Needs Left Unaddressed

While it is essential to continue studying treatment for MS, patients and their caregivers have other daily challenges that need to be addressed, as well.

“Addressing physical activity and diet and having conversations around holistic care with clinicians—that wasn’t the case 10 years ago,” explained Tim Coetzee, Ph.D., chief advocacy, services and research officer at National Multiple Sclerosis Society and a panelist at the recent discussion. “We want to approach innovation holistically by looking for tools that are useful not just to those who want small bites, but also to those who want it all.”

For instance, 28 percent of people with MS surveyed in one study said that psychological support was their most significant unmet need. “I lived in denial for years—I didn’t tell my friends or coworkers that I had a chronic illness,” Elizabeth Jones said during the panel. “I really needed to connect with people.”

Like people with MS, caregivers also experience high levels of stress and are often referred to as the “hidden patients” of the disease. But now, we’re seeing increased awareness of the burden of the disease on caregivers, according to Amanda Montague, Ed.M., vice president of Education and Healthcare Relations at the Multiple Sclerosis Association of America.

“We’re seeing a focus on the holistic experience of MS and bringing care partners into conversations,” she said during the panel discussion. “I’m excited to see innovations that incorporate care partners in both clinical and home settings.”

No one understands what it’s like to have MS
other than another person who has it.

Overcoming Information Overload

During the discussion, panelist Darin T. Okuda, M.D., M.S., director of the Neuroinnovation program and director of the Multiple Sclerosis & Neuroimmunology Imaging program at the University of Texas Southwestern Medical Center in Dallas, explained that because every individual with MS has a different experience of the disease, there are many opportunities for innovation to improve the lives of patients.

As an example, Okuda explained that he realized patients were coming to their appointments with him often feeling overwhelmed by the amount of information available on the Internet about their disease and confused by which resources to trust.

So Okuda and his team developed an app, called Pre-Meet: Multiple Sclerosis, to help patients prepare and focus on what is essential before appointments with their MS specialist to make the most of those visits. The app lets them know what to expect during their exam and understand the next steps following the appointment.


DARIN T. OKUDA, M.D., M.S. FROM THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER IN DALLAS AND HIS TEAM DEVELOPED AN APP, CALLED PRE-MEET: MULTIPLE SCLEROSIS, TO HELP PATIENTS PREPARE FOR THEIR APPOINTMENTS WITH THEIR MS SPECIALIST.

 

“Responsible and reliable content is key,” Okuda said. “When a patient has way too much information, we often find that they define themselves by their disease, which we don’t want them to do.”

While all the panelists at the event brought their own unique perspectives and priorities to the discussion, they all agreed that the MS space is ripe for innovation and that those directly impacted by the disease – patients, caregivers and experts in the field – can lead the charge.

To learn more about the Lyfebulb-Celgene 2019 “Addressing Unmet Needs in MS: An Innovation Challenge” or to apply for the Challenge, visit the Lyfebulb web page.

Over the past few decades, scientists have come to understand that the loss of brain tissue—categorized into grey and white matter—in people with multiple sclerosis (MS) is linked with disease worsening. But research is revealing that grey matter loss, in particular, may be closely associated with disability and cognitive impairment.

“Grey matter loss is one of the best predictors of disease progression in people with MS,” said Dr. John DeLuca, senior vice president for research and training at the Kessler Foundation. “Finally, we’re seeing data that may help us better understand the mechanisms that drive this disease.”

DeLuca is calling attention to the value of assessing grey matter and cognitive impairment in MS and what implications these findings may have in understanding the disease.

JOHN DELUCA, Ph.D.

JOHN DELUCA, Ph.D., FROM THE KESSLER FOUNDATION BELIEVES GREY MATTER LOSS IN THE THALAMUS CAN PREDICT COGNITIVE DECLINE IN PEOPLE WITH MS.

Grey Matter Loss Associated With MS Disability Progression

While researchers have known that grey matter loss is associated with long-term disability, a study published earlier this year has provided a more detailed picture of that connection.

The researchers looked at how specific patterns of grey matter loss were associated with disability progression in patients with MS using a standard MS disability scale (EDSS).

The researchers found the strongest relationship between disability progression and the loss of brain tissue in the thalamus, the largest area of deep grey matter, which transmits sensory information to other areas of the brain. In a post-hoc analysis of MRIs from 1,214 MS patients and 203 healthy controls, baseline thalamic volume loss increased risk of disability progression by 37 percent in relapsing MS.

“The research continues to provide more evidence that loss of grey matter is associated with increased disability,” he said. “And grey matter loss is seen most intensely in the thalamus of patients with MS.”

Probability of Disability Progression Due to Volume

Cognitive Impairment Shouldn’t Take a Backseat to Disability

The new study makes the case for grey matter loss as a predictor of disability progression in MS, but it did not look at cognitive function—which can also worsen as MS progresses. DeLuca wasn’t surprised. “Cognitive impairment just doesn’t get the same attention as disability in MS studies,” he said. “But it really should.”

Many patients agree. In a recent survey conducted by the Multiple Sclerosis Association of America and sponsored by Celgene, 27 percent of respondents said maintaining cognitive function was the most important consideration in the management of their MS. Only the prevention of disability progression was reported by more respondents (45 percent).

While cognitive impairment has been recognized in MS for more than a century, a test to measure cognitive function wasn’t developed until 2001. Researchers know that up to 65 percent of people with MS experience some level of cognitive impairment, and the National MS Society recently announced new recommendations for managing cognitive care for people with MS.

So could the same patterns of grey matter loss associated with disability also be related to cognitive impairment? It’s quite possible, according to DeLuca. “Thalamic damage already has an established relationship with cognitive decline,” he pointed out. “And grey matter loss is seen most intensely in the thalamus of patients with MS. So it’s probable.”

The more specific we can be regarding the role of grey matter loss, the better we can care for patients with MS.

Measuring Grey Matter Loss in Practice

So far, doctors don’t routinely use grey matter loss as a predictor of disability or cognitive impairment when caring for patients, but DeLuca believes that maybe they should consider it. “Grey matter loss could be a trigger for clinicians to watch their patients over time and monitor for potentially related problems,” he explained.

Given current evidence, DeLuca would like to see more trials differentiating grey matter loss from brain volume loss in general. But the main goal, of course, is to identify new ways to look at cognitive impairment. DeLuca is hopeful.

“I think we’ll start to see further research that show the correlation between grey matter and cognitive impairment as well as physical disability,” DeLuca said. “The more specific we can be regarding the role of grey matter loss, the better we can care for patients with MS.”

To learn more about how brain volume loss can affect patients with MS decades later, read “How Multiple Sclerosis Affects the Brain and CNS.”

For decades, researchers seeking to develop new treatment options for multiple sclerosis (MS) believed that it was primarily a disease of the brain’s white matter, but recent studies have highlighted that grey matter plays an important role as well. For instance, grey matter loss, known as atrophy, may be seen in early stages of the disease and is associated with worsening symptoms.

As part of this year’s efforts to raise awareness of the disease during World MS Day on May 30, Dr. Robert Zivadinov, professor of Neurology and director of the Buffalo Neuroimaging Analysis Center and Center for Biomedical Imaging at Clinical Translational Science Institute at the University of Buffalo, explains researchers’ evolving understanding of the role of grey matter damage in MS.

DR. ROBERT ZIVADINOV FROM THE UNIVERSITY OF BUFFALO BELIEVES UNRAVELING THE ROLE OF GREY MATTER IN MULTIPLE SCLEROSIS MAY HAVE IMPLICATIONS FOR FUTURE TREATMENTS.

DR. ROBERT ZIVADINOV FROM THE UNIVERSITY OF BUFFALO BELIEVES UNRAVELING THE ROLE OF GREY MATTER IN MULTIPLE SCLEROSIS MAY HAVE IMPLICATIONS FOR FUTURE TREATMENTS.

MS was previously considered to affect white matter primarily. How has that understanding evolved to include grey matter?

“About 15 years ago, improved imaging techniques revealed that large areas of grey matter were affected in patients. This evidence helped explain why some patients had such severe disease but relatively few damaged areas in the white matter, known as lesions.”

Are there specific regions of grey matter that are affected by MS?

“Not all parts of the grey matter are equally affected. There’s definitely significant involvement of the cortical layers of the brain’s grey matter, which is linked to symptoms such as fatigue, cognitive changes and memory loss.

“The deep grey matter is also involved in MS as well, and in particular the thalamus, which relays motor signals and regulates things like consciousness, sleep and alertness.”

“Some studies have found that grey matter atrophy correlates with disability, cognitive impairment and disease progression better than white matter.”

What do researchers know about the connection between the loss of grey matter, cognitive dysfunction, disability and MS progression?

“Many studies have found links between grey matter damage with both physical and cognitive impairment in patients with MS, including symptoms such as muscle control, sensory perception and memory. Some studies have found that grey matter atrophy correlates with disability, cognitive impairment and disease progression better than white matter lesions do.

“Studies also suggest that grey matter lesions occur rather early on, particularly in relapsing-remitting MS, even before white matter lesions appear. It could very well be a potential marker for predicting disease progression.”

What is preventing it from becoming a more useful predictor of disease progression?

“Grey matter lesions are less pronounced than white brain lesions, so doctors have difficulty seeing them on typical MRIs. Instead, we have to use advanced, highly sensitive MRI techniques to measure changes in grey matter, but those techniques aren’t available everywhere. They require specialized equipment and expertise that is typically only found in academic research centers. That is one reason why grey matter atrophy has had limited use in the clinic.”

What do we still not understand about grey matter atrophy in people with MS?

“We still don’t understand what causes the damage. Grey matter atrophy is associated with several genetic, viral and environmental risk factors, but we haven’t pinpointed the mechanisms yet.”

What can be done to reduce the risk of damage to grey matter?

“That’s the holy grail. Most MS trials weren’t necessarily designed to answer that question. We are going to have to change the design of MS trials. Instead of only using MRIs of white matter lesions as an endpoint, we’ll need more sensitive imaging techniques to monitor grey matter changes over time as well.”

To learn more about how MS affects the brain over a lifetime, read “How Multiple Sclerosis Affects the Brain and CNS.”

Dr. Robert Zivadinov is a paid consultant for Celgene.

When Dr. Timothy Vollmer sees patients with multiple sclerosis (MS), they talk about the symptoms they are experiencing today. But Vollmer tries to get them thinking further down the road. Most people with MS are diagnosed between the ages of 20 and 40, but might not feel the full impact of the disease until their 60s.

“The best bet at slowing the progression of disability later in life is at the beginning of the disease,” said Vollmer, a neurologist at the University of Colorado Denver. “But many patients — and even neurologists — don’t fully understand how MS affects the brain over a lifetime and why brain preservation is important.”

The Death of the Neurons

DR. TIMOTHY VOLLMER FROM THE UNIVERSITY OF COLORADO DENVER BELIEVES THAT THE BEST WAY TO SLOW DISABILITY PROGRESSION LATER IN LIFE IS TO TREAT MULTIPLE SCLEROSIS EARLY.

DR. TIMOTHY VOLLMER FROM THE UNIVERSITY OF COLORADO DENVER BELIEVES THAT THE BEST WAY TO SLOW DISABILITY PROGRESSION LATER IN LIFE IS TO TREAT MULTIPLE SCLEROSIS EARLY.

Damage in the brain for patients with MS is driven at least in part by a critical component of the immune system called B lymphocytes, also known as B cells, which recruit other immune cells and cause an inflammatory reaction. Why B cells begin attacking neurons is not fully understood, but what can be clearly seen is the damage they leave behind in the form of lesions that appear as bright white spots on a patient’s magnetic resonance imaging (MRI) scan.

When Vollmer analyzes a patient’s MRI, he pays particular attention to the appearance of lesions in the grey matter of the brain, the region involved in muscle control and sensory perception. As the grey matter continues to be attacked, causing new lesions to develop, symptoms such as fatigue and memory loss become more common, and cognitive impairment tends to increase.

But lesions often don’t appear steadily and consistently throughout a patient’s lifetime. Instead, the number of lesions tends to be highest at the onset of MS and then decreases over time. By the time a person with MS reaches 60 years old, new lesions are relatively rare.

“We don’t know why these lesions appear to decrease over time,” Vollmer said. “But if we wait to treat patients, the damage has already been done and what we’re left with is an accelerated pace of brain volume loss.”

Neurological Reserve

By the age of 40, everyone’s brain begins shrinking due to the loss of neurons as a result of the normal aging process. However, brain shrinkage happens faster in people with MS; while healthy individuals lose 0.1 to 0.5 percent of their brain volume per year, people with MS lose 0.5 to 1.35 percent per year, a significantly faster rate than those without the disease.

It’s important that neurologists understand how MS affects the brain throughout a person’s lifetime.

The effects of this brain volume and neuron loss may not be immediately apparent, though, because their brains and central nervous system tap into a neurological reserve to supplement this decline. However, those reserves are then used up sooner and, coupled with the normal aging process, result in the increased cognitive impairment and disability seen in people with MS.

With this long-term understanding of how MS affects the brain and CNS, Vollmer is traveling to conferences, giving lectures and trying to drive an international consensus on the issue. He’s reminding his patients and colleagues that it’s important to focus on measuring not only relapses, but also lesions and brain volume loss.

“It’s important that neurologists understand how MS affects the brain throughout a person’s lifetime,” Vollmer said. “Then they will understand why treating patients early and encouraging healthy lifestyles is essential to improving their patients’ lives down the line.”

To learn more about the MS journey for patients, read “The Search Continues for More Multiple Sclerosis Treatment Options.”

 

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When he started his career in medicine over 25 years ago, Dr. Jack Burks had no treatments for his patients with multiple sclerosis (MS). So when the first MS treatment was approved in 1993, he was grateful to finally have something — anything — to prescribe for one of his patients who had a severe form of the disease. Twenty years later, that patient is still doing well on that same medication and has yet to suffer a relapse.

Stories such as this one help demonstrate the impact that progress in research can make on patients’ lives. But Dr. Burks, the chief medical consultant at the Multiple Sclerosis Association of America (MSAA), knows that there are still many unmet needs. Although 15 therapies have been approved for the treatment of MS, none offer a cure, and, as with all treatments, there are potential risks to consider. In this Q&A, Dr. Burks provides his perspectives on the current state of MS treatment and why he remains optimistic about the future.

DR. JACK BURKS, THE CHIEF MEDICAL CONSULTANT AT THE MULTIPLE SCLEROSIS ASSOCIATION OF AMERICA, KNOWS THAT THERE ARE STILL MANY UNMET NEEDS IN MULTIPLE SCLEROSIS.

DR. JACK BURKS, THE CHIEF MEDICAL CONSULTANT AT THE MULTIPLE SCLEROSIS ASSOCIATION OF AMERICA, KNOWS THAT THERE ARE STILL MANY UNMET NEEDS IN MULTIPLE SCLEROSIS.

What is the treatment journey like for people with MS?

“The MS treatment journey for patients can fall into a pretty broad spectrum. For some patients, treatment goes smoothly. The response is excellent, and everything goes well. But for others, it can be a struggle.

“While we have several therapies available, we cannot guarantee that they will work for a particular patient. So we go with what we think will work best, and if it doesn’t work out, we may recommend switching therapies. That change, of course, can be stressful and confusing for patients. But without treatment, the disease will worsen, and patients will only experience further impairment.”

When should a patient and their doctor consider switching therapies?

“Doctors usually recommend changing therapies for one of two reasons: safety or efficacy. Either the patient cannot tolerate the treatment because of side effects, or the treatment is no longer controlling the disease.

“Patients tend to focus more on the side effects. They might not see the brain lesions in magnetic resonance imaging, but they do know if they get sick every time they take a medication. Side effects scare them.

“But switching therapies should not be an immediate reaction to those side effects. If someone has mild injection site reactions, the doctor can recommend applying a warm compress. If they experience gastrointestinal problems, their doctor might suggest taking the medication at a different time of the day.”

What can help smooth out the journey for people with MS?

“A good doctor-patient relationship is essential to managing treatment expectations and side effects alike. Patients need to know and feel that their doctor is looking out for their best interests. Doctors need to understand a patient’s priorities and communicate in a way that builds trust.

“Patients need to become knowledgeable about their disease before their first appointment. They should prepare a list of questions to discuss with their doctor. There are no wrong questions. Doctors and patients should share treatment decisions, which helps patients own their treatment and can improve adherence.”

We’re doing pretty well even though we don’t know the cause of the disease. The future looks very bright for new MS treatments.

How does patient preference factor into MS treatment decisions?

“Doctors need to talk with their patients about their preferences. Some patients do not mind if their treatment is a pill or an injection, while others have stronger opinions.

“Doctors need to understand a patient’s specific concerns because if not, that’s an equation for poor adherence.”

When should doctors bring up MS clinical trials with their patients?

“One of the first questions my patients ask me is ‘What’s new?’ They want to know about the new options that are approved or being developed. So doctors need to know about the trials that are ongoing. I try to focus on trial results, side effects and contraindications with other medications.

“Patients might not be interested in enrolling in a trial, especially if their current treatment is working for them, but often they just want to know what is in the future of MS treatments and how it may affect their treatment down the line.”

What is your view of the future of MS treatment?

“I’m pretty optimistic. We’re doing pretty well even though we don’t know the cause of the disease. The future looks very bright for new MS treatments.

“When I look at these new medications, I consider not only how well a therapy reduces relapse rates, but also the safety profile. Side effects, as I mentioned, are one of the reasons why patients stop taking their medication. Right now, I am reviewing over 20 new therapies that are in trials and have the potential to help so many more people than we already are.”

To learn more about how researchers are studying new MS treatments, read “Relapse Rates: A Benchmark for Measuring MS Treatment Efficacy.”

Measuring the effectiveness of treatments for multiple sclerosis (MS) is complicated; the disease biology is not entirely understood, and symptoms vary from person to person. While doctors and researchers continue to explore new endpoints for clinical trials that evaluate MS therapies, measuring relapse rates remains one of the most common.

Neurologist Enrique Alvarez, M.D., Ph.D., at the University of Colorado, Denver, discusses the importance of continuing to evaluate potential new therapies based on their ability to reduce relapse rates, along with newer measures that are bolstering these evaluations.

How do researchers measure the efficacy of new treatments for MS?

NEUROLOGIST ENRIQUE ALVAREZ, M.D., PH.D., AT THE UNIVERSITY OF COLORADO, DENVER, EXPLAINS WHY RELAPSE RATES HAVE REMAINED A BENCHMARK IN MS TRIALS.

NEUROLOGIST ENRIQUE ALVAREZ, M.D., PH.D., AT THE UNIVERSITY OF COLORADO, DENVER, EXPLAINS WHY RELAPSE RATES HAVE REMAINED A BENCHMARK IN MS TRIALS.

“Relapse rates are a benchmark for measuring the efficacy of new MS treatments in clinical trials. A relapse occurs when a new neurological symptom emerges or an old symptom gets worse for at least 24 hours. MS can cause a variety of symptoms such as vision loss, pain, fatigue or impaired coordination.”

“Signs of a relapse can be reported by the patient, and may have an immediate impact on the quality of a patient’s life. Relapse rates also tend to go hand-in-hand with disability rates; relapses are often associated with some lasting disability.”

How else are researchers measuring efficacy in MS?

“We have set criteria about how to determine a relapse, but these assessments are often subjective and can be ‘noisy.’ This noise can be associated with a pseudo-relapse, which is the return of an old symptom because of factors unrelated to MS, such as stress, fever or an infection. MS symptoms can also fluctuate throughout the day, affecting a patient’s assessment.” 

“The challenge is finding a way to measure clinical events across all the patients in a study. For example, how do you compare a patient who might have bladder function issues with a patient who has vision loss? That type of comparison remains a challenge.”

These newer measurements are valuable, but we still need to look at relapse rates.

How are researchers overcoming the challenges of measuring efficacy in MS trials?

“We have been including more objective, less noisy measures such as MRI [magnetic resonance imaging] metrics in trials. MRI measurements can serve as a substitute for clinical outcomes reported by patients.”

“In MS, the body’s immune system causes inflammation and damage in the brain, resulting in scar tissue, which we call a lesion. MRI can measure new and growing lesions in the brain. The more lesions a patient has, the more likely he or she will experience worsening symptoms and future relapses.” 

SECONDARY MEASUREMENTS SUCH AS MRI BRAINS SCANS CAN HELP MEASURE THE EFFICACY OF NEW MS TREATMENTS.

SECONDARY MEASUREMENTS SUCH AS MRI BRAINS SCANS CAN HELP MEASURE THE EFFICACY OF NEW MS TREATMENTS.

What are some newer measures that are being explored?

“Newer measures are exploding. We’re starting to see a host of cognitive testing measures. Balance is being evaluated more. There are kinetic measures, like those you can find on a smartphone app, to see how much the patient is walking. We’re trying to get a sense of how the patient feels their life is changing on the tested therapy. You lose a little of the objectivity that you get with a measurement like MRI, but you gain a better sense of how the patient feels they’re doing.”

Could these newer measurements replace relapse rates as a benchmark?

“These newer measurements are valuable, but we still need to look at relapse rates. Rather than replace them, we’ll be more likely to see combinations of multiple endpoints used to determine the efficacy of tested therapies in trials. The more measurements, the better.”  

To learn about how relapses can affect the lives of people living with MS, read “World MS Day: MS Doesn’t Stop Me from Living a Life I Love.”

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SARAH CANTU (TOP RIGHT) IS LIVING WITH MULTIPLE SCLEROSIS BUT DOESN’T ALLOW THE DISEASE TO DEFINE WHO SHE IS. SHE CONTINUES TO ENJOY LIFE WITH HER FAMILY DESPITE THE LIMITATIONS OF HER DISEASE.

SARAH CANTU (TOP RIGHT) IS LIVING WITH MULTIPLE SCLEROSIS BUT DOESN’T ALLOW THE DISEASE TO DEFINE WHO SHE IS. SHE CONTINUES TO ENJOY LIFE WITH HER FAMILY DESPITE THE LIMITATIONS OF HER DISEASE.

While having multiple sclerosis (MS) frames most everything in life for people with MS and their families, many find ways to adjust despite the limitations they may experience personally. Just ask Sarah Cantu and her family, for example. When her 8-year-old son learned his school was holding a mother and son sports night earlier this year, he understood his mother couldn’t do an obstacle course and other activities because she wouldn’t be able to run as she liked to do. So instead, he invited his mother out for a movie night.

On World MS Day (May 31), as we celebrate the strength of those facing the disease, Cantu wants to help others understand what life with MS means to her and how she continues to live the life she loves.

How did you learn that you had MS?

I woke up one morning in December 2012, and the right side of my face was numb. I thought I had just popped a disc the day before. But the next day, the entire left side of my body was numb. I thought I’d had a weird stroke.

I met with a neurologist and got an MRI. My doctor said I had an abnormality in my brain, either a tumor or MS. She planned a spinal tap the next week.

3 out of 4 people living with MS experience severe fatigue, making it one of the most common symptoms. By Monday morning, I couldn’t walk or swallow. My head was foggy. I went to the emergency room where the doctor did a spinal tap and diagnosed me with MS. Fortunately, I have regained most of what I lost with that first flare four and a half years ago. I was 31 at the time with two young kids.

The theme for World MS Day 2017 is ‘Life with MS.’ What does living with MS mean for you?

Living with MS is part of who you are but not all of you. MS doesn’t stop me from living. I’m a mom. I have a life. It just shifted a bit.

There are more good days than bad. Sometimes people assume the worst is going to happen. I had two and a half years between relapses, and I may have two and a half more before the next. Sometimes people are afraid to ask if it’s a good or bad day; assume good unless I say otherwise.

I don’t know any other disease that affects people so individually. Heat triggers my disease, but some people with MS live in Arizona with no heat problems at all.

Living with MS is part of who you are but not all of who you are. MS doesn’t stop me from living.

How has MS affected your ability to work or remain employed?

After I had recovered from my first relapse, we got into a groove. I went back to school and got my master’s degree last December. I was working part-time while in school, and I’m currently looking for a job.

Mentally, I had to get over the block of not being able to do things because of the disease. Once I did that, I got my master’s within a year.

Anxiety, stress and depression can all play a role in the lives of people with MS. How have you dealt with these feelings?

I think everyone with MS goes through them. We’re active in our church and have strong faith, which helps with the bigger picture.

For me, writing is a big stress relief—getting something on paper so it no longer has to swim in my head.

We live close to the ocean, and I visit often because it’s impossible to be stressed at the beach. My neurologist also encouraged me to get a few hours of “alone time” each week.

What has helped you cope with the physical limitations of MS?

I’ve had to slow down and plan more. I have to prepare for things differently, like my daughter’s upcoming all-day lacrosse tournament. It will be 85 degrees outside; so looking through my MS lens, I’ll need cooling equipment and a plan for taking breaks.

To combat my fatigue, I make lots of crock-pot meals, so I can make dinner in the morning when I have energy.

SARAH CANTU (RIGHT) COPES WITH THE EMOTIONAL AND PHYSICAL STRESS OF LIVING WITH MULTIPLE SCLEROSIS BY BEING PART OF HER CHURCH COMMUNITY, WRITING AND TAKING WALKS ON THE BEACH. SARAH CANTU (RIGHT) COPES WITH THE EMOTIONAL AND PHYSICAL STRESS OF LIVING WITH MULTIPLE SCLEROSIS BY BEING PART OF HER CHURCH COMMUNITY, WRITING AND TAKING WALKS ON THE BEACH.

What would freedom from MS mean for you in real, everyday terms?

I could run again! I used to work out two hours a day. Now, I’m limited to walking. I’m not allowed to run because of an imbalance in my legs. I’d like to be able to play kickball with the kids, run the bases and play lacrosse.

1 out of 3 people living with MS have persistent visual impairments.Freedom from MS would release me from worrying that I was having a flare-up if I experienced a new symptom.

What are your thoughts on the progress that’s being made in the understanding of the disease and its treatment?

When I was diagnosed, my neurologist told me this wasn’t a death sentence; it’s a chronic illness. Those who are newly diagnosed don’t always know the progress of the last 15 years. When I was diagnosed, there were 11 medications. Now, there are 17. If one stops working, I know there are others. It’s amazing.

I’m hopeful a cure will happen in my lifetime so that I won’t have to worry about whether my kids end up with MS. I hope that someday, you can take a pill and be done.

To learn more about how a better understanding of the most common type of MS, relapsing-remitting, could lead to new treatments, read “Big Questions Continue to Drive Multiple Sclerosis Research.”

BRUCE BEBO, PH.D., EXECUTIVE VICE PRESIDENT OF RESEARCH AT THE NATIONAL MS SOCIETY, BELIEVES THAT ADVANCES IN MS TREATMENT ARE ENCOURAGING.

BRUCE BEBO, PH.D., EXECUTIVE VICE PRESIDENT OF RESEARCH AT THE NATIONAL MS SOCIETY, BELIEVES THAT ADVANCES IN MS TREATMENT ARE ENCOURAGING.

While treatment for multiple sclerosis (MS) has improved over the past 20 years, there’s still no cure. Most people living with MS have a form of the disease called relapsing-remitting MS (RRMS) with cycles of relapses (when symptoms flare up) followed by periods of remission (times of little or no symptoms). But researchers now better understand the pathways that contribute to MS relapses, and that knowledge is driving the development of new treatments.

During this year’s MS Awareness Month (March), we spoke with Bruce Bebo, Ph.D., executive vice president of Research at the National MS Society, to understand the questions driving MS research today and the progress being made.

The National MS Society is funding more than 300 research projects and invests about $50 million in MS research each year. What are some of the most exciting recent advances?

Advances in repairing the myelin sheath, which protects nerve cells and is destroyed by MS, are encouraging. This approach has tremendous promise to work with immunotherapies to stop the disease from getting worse. MS is an autoimmune disorder in which the body’s immune system attacks and destroys nerve cells; so immunotherapies may ultimately slow down or halt the neurodegeneration in MS. A better understanding of the role of B cells (a type of immune cell) play in this destruction will likely lead to new and improved treatments for this type of MS.

Most of the 2.3 million people worldwide with MS have a type called relapsing-remitting MS (RRMS). What are the big questions that are driving research in RRMS? 

We still don’t know the precise targets that the immune system recognizes in RRMS, the environmental risk factors and triggers or how the estimated 200 genes that have been associated with MS actually contribute to the disease.

How will answering these questions help lead to more effective treatment options for patients with RRMS?

Immunotherapies today often affect immune cells that fight infection as well as those that cause MS. Knowing the targets will allow us to develop more precise therapies that will prevent the immune system from attacking nerve cells but not interfere with fighting infections. Understanding the environmental lifestyle factors and genetic factors will also reveal pathways and strategies for treatment and prevention.

There will always be some people who respond and others who do not. Having more options will allow doctors to personalize therapies for people living with RRMS.

With over a dozen available treatment options, why do we need more for RRMS?

There will always be some people who respond to specific treatments and others who do not. Having more options will allow doctors to personalize therapies for people with RRMS. Another reason is that our best treatments today only inhibit relapses by about 50 percent. We can do better than that! And more targeted immunotherapies could help stop the progression of RRMS without leaving a person with MS vulnerable to infections.

How important is a person with MS’s role in RRMS research and clinical trials?

The only way we can make progress in MS is by studying people with the disease. Patient-centered research efforts are gaining momentum. One of those efforts is the iConquerMS program, which is collecting data from 20,000 people about their lives with MS and their treatment responses. This will help answer questions about how environmental and lifestyle factors influence MS. People with MS can also take part in clinical trials of new MS therapies. They can find out about these at the National MS Society website.

The vision of National MS Society-funded research is to move us closer to a “World Free of MS.” While we are still searching for a cure, what does freedom from MS mean for people with the disease in real-life terms?

Freedom means something different to every individual living with MS. To some it simply means having the energy to enjoy dinner with their family at the end of the day. For others, it means being able to enjoy activities such as hiking, biking or painting.

Discovering a new therapy is no easy task, and Esther Martinborough, executive director of research at Celgene, knows this firsthand. In 2008, she saw Receptos’ two therapeutic candidates for cancer fail before her team rallied to identify a potential new treatment option for multiple sclerosis (MS). Aided by the 2015 acquisition of Receptos by Celgene, her team is committed to bringing this potential new treatment option to MS patients.

In this Q&A, Martinborough explains that the company’s quick turnaround was due to two factors: the right team and a smarter way to screen therapeutic candidates.

Our Commitment to Multiple Sclerosis

ESTHER MARTINBOROUGH (FAR LEFT) EXECUTIVE DIRECTOR OF RESEARCH AT CELGENE< AND HER COLLEAGUES REVIEW DATA REGARDING THE COMPANY’S THERAPEUTIC CANDIDATE FOR MS.

What was Receptos’ original focus?

When the company was founded in 2008, we were called Apoptos and were focused on several exciting opportunities to develop anticancer therapies. After six months of preclinical research, it became apparent that we could not move forward. The scientific rationale was not holding together, and we explained this to our investors. Fortunately, our investors recognized we had a very qualified team with multiple individuals who had brought treatments to the market successfully. Based on that expertise, our investors put their trust in us and gave us another chance, so we worked as a team to carefully make sure our next hypotheses had the best chances of getting to the clinic. We were thorough, looking closely at multiple compounds and how they worked. We looked at a wide variety of candidates that were scientifically interesting.

Why did you choose to focus on a sphingosine-1-phosphate (S1P) modulator for MS?

There was a good biological rationale. Other S1P modulators were already in the clinic for MS, so we knew it could work. While the S1P compounds we evaluated weren’t quite ready for the clinic, we saw an opportunity to get them there quickly.

The S1P modulators that were ahead of us in clinical development, for the most part, had similar structures. We decided not to go down that same path.

How long has the development process taken?

We started working on our S1P modulator in March 2009 and were in the clinic less than two years later, which is quite simply astounding. When we began developing S1P modulators, about 20 other companies were ahead of us. Today, we’re one of the leaders in the pack.

How did you accelerate the development?

The difference was our screening approach. Most companies move step-by-step in screening candidates: they test the efficacy and then move onto studying the side effects and toxicology. We consolidated these steps into just one experiment. Using a biomarker for S1P as a preclinical measure of efficacy and lung weight in an animal model to measure safety, we were able to pick the therapeutic candidates with the right potential balance of efficacy and safety quickly.

ESTHER MARTINBOROUGH (RIGHT) AND A COLLEAGUE AT CELGENE DISCUSS THE CHEMICAL STRUCTURE OF THE COMPANY’S S1P MODULATOR THAT IS CURRENTLY IN CLINICAL DEVELOPMENT FOR MS.

ESTHER MARTINBOROUGH (RIGHT) AND A COLLEAGUE AT CELGENE DISCUSS THE CHEMICAL STRUCTURE OF THE COMPANY’S S1P MODULATOR THAT IS CURRENTLY IN CLINICAL DEVELOPMENT FOR MS.

What made this S1P modulator stand out from the others being developed?

The S1P modulators that were ahead of us in clinical development, for the most part, had similar structures. We decided not to go down that same path because that would likely only lead to the same safety and efficacy profiles. Instead, we designed chemical structures in our S1P modulator that were different from those already reported. We looked to map out a unique chemical space that could benefit MS patients.

Learn more about the role of S1P signaling molecules in MS and other immune-inflammatory diseases, read “Corralling White Blood Cells to Rein in Multiple Sclerosis.”

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Neurologist Bruce Cree at the University of California, San Francisco Medical Center believes that more therapies are needed to help MS patients remain independent.  

NEUROLOGIST BRUCE CREE AT THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO MEDICAL CENTER BELIEVES THAT MORE THERAPIES ARE NEEDED TO HELP MS PATIENTS REMAIN INDEPENDENT.

As the theme of this year’s World MS Day is “independence,” it’s fitting to remember that for the more than 2 million people around the world with multiple sclerosis (MS), small gains in treatment effectiveness can mean big gains in quality of life and independence.

MS is a chronic neurological disorder that’s usually diagnosed in early adulthood—between the ages of 20 and 40—and that often gets progressively worse over the following decades. Symptoms vary over time and among patients but include fatigue, vision and speech problems and impaired coordination—all of which can make doing everyday activities like eating, bathing and dressing challenging.

In one survey, 65 percent of people with MS said mobility was the greatest challenge related to the disease. Others ranked fatigue, pain and muscle spasms as the most debilitating aspects. Indeed, 80 percent of MS patients will experience some degree of impaired mobility within 10 to 15 years of being diagnosed with the disease.

“MS tends to affect people at the prime of their lives when they are busy working and raising families,” Dr. Bruce Cree, a neurologist at of the University of California, San Francisco Medical Center, said. “As a consequence of the neurological impairments of the disease, people often lose their ability to work.”

World MS Day 2016: Toward a Greater Sense of Independence

Indeed, 55 percent of patients in one study were unable to stay employed following diagnosis. The economic costs of the disease—including medical care and lost productivity—are huge, estimated at $10 billion per year in the United States alone.

Over time, patients become reliant on family and caregivers to help them carry out even the most basic tasks, like going to the bathroom. Depression, social isolation, strained family relationships and divorce are all common in MS patients, according to Dr. Cree.

There is no cure for MS, but a growing number of therapies help prevent symptom flare-ups and slow the progression of the disease. While most previous MS drugs were injections, some newer therapies come in convenient pill form.

New therapies can certainly improve the quality of life for many patients.

“New therapies can certainly improve the quality of life for many patients,” said Cree. “Not only have studies found that patients greatly prefer pills to injections.”

Still, no existing treatment addresses the greatest burdens of the disease for patients with advanced MS—fatigue and cognitive impairment.

“An MS patient might look like everyone else,” said Dr. Cree. “There’s not always something on the surface that tells you they have MS. But their quality of life can be greatly impacted by aspects of the disease that are not obvious.”

To improve the quality of life, future therapies to treat MS must not only slow the progression of disease but also enable patients to be more independent and boost quality of life.

While improvements in the treatment of multiple sclerosis (MS) have focused on reducing the frequency of flare-ups, preventing MS-related disability has remained a struggle. Multiple sclerosis and other immune-inflammatory diseases can flare up when white blood cells go rogue—exerting their inflammatory effects where they shouldn’t. Scientists have recently identified methods to corral these rogue cells, lessening their ability to inflict damage, by blinding them to the signposts that lead them astray. The latest research now aims to refine this method, to lessen potentially dangerous side effects.

Unwanted, uncontrolled inflammation can wreak havoc in the body. It’s at the root of multiple sclerosis and countless other disorders, including Crohn’s disease and ulcerative colitis. Research has shown that the damage can be partly blamed on an invasion of white blood cells called lymphocytes. As a result, several strategies have been devised to interfere with their migration to inflammation sites.

In one such strategy, lymphocytes are made “blind” to the signals that lead them out of hiding and send them off in search of inflammation. When they aren’t off finding enemies to fight, lymphocytes can often be found hanging out in lymph nodes, where they are relatively harmless. But they can be lured out of nodes by a signaling molecule called sphingosine 1‐phosphate (S1P). Nodes have little S1P, while the blood vessels they sit near have much more S1P, and the white blood cells follow the trail of S1P to escape their hiding spots.

Lymphocytes can be lured out of nodes by a signaling molecule called sphingosine 1‐phosphate (S1P).

Once in the bloodstream, lymphocytes are free to wander to places where they might do damage—like an inflamed intestine, in the case of Crohn’s disease, or a vulnerable neuron, in the case of multiple sclerosis. But their escape from lymph nodes can be blocked by modulating the receptors that sense S1P, known as the sphingosine 1‐phosphate receptor (S1PR) family.

Therapies that interfere with S1PR aim to trap lymphocytes in lymph nodes, reducing their numbers in the bloodstream and tissues. And at least one such therapy has been successful in treating certain forms of multiple sclerosis.

Interfering with the S1PR family can have its drawbacks, though. For instance, since one S1PR member is involved in cardiac function, patients have to be monitored for several hours after their first dose, to ensure their heart continues to work properly. As a result, researchers are looking for therapies that more specifically target only the S1PR members that let lymphocytes out of nodes. The aim is to improve the reduction in inflammation while also reducing the chances of potentially dangerous side effects.

G-protein-coupled receptors

Members of the S1PR family belong to a class of membrane receptors known as G-protein-coupled receptors (GPCR). These proteins are like signal transducers—taking messages from the environment in the form of sugars, fats, protein and even light and translating them into changes inside cells.

Humans have almost 1,000 different GPCRs, and each recognizes and responds to a particular signal. They have so many different functions that it’s thought between a third and a half of all marketed drugs act by binding to GPCRs.

GPCRs have a very distinctive shape and structure: a protein chain that wraps back and forth seven times from the outside of the cell to the inside and back. The loops facing out of the cell form a landing site for signaling molecules. Inside the cell, GPCRs interact with the partners that give the receptors their name: G proteins.

G proteins are like on-off switches that can be flipped depending on the state of its GPCR. G proteins have three parts: α, β and γ. When the three are bound together with their GPCR, α binds a compound called guanosine diphosphate (GDP), which keeps it in an “off” state.

When the right signal outside the cell—a sugar, for example—binds to the GPCR, the receptor changes shape, kicking α and its GDP out of the group. The change also causes GDP to be replaced with guanosine triphosphate (GTP), which creates an “on” state. It’s this active α subunit that travels through the cell turning on specific cellular activities.

Back at the cell membrane, the now lonely β and γ portions of the G protein also relay messages into the cell. For instance, they can activate (or inhibit) enzymes or open up (or close) ion channels. The resulting metabolic changes allow the cell to respond to an ever-evolving environment.