MS Trial Alert: Investigators Recruiting People with Relapsing-Remitting Multiple Sclerosis for Study Adding a Potential Myelin Repair Therapy to Disease-Modifying Therapy

 Summary: Researchers at 25 sites across the United States are recruiting 168 people with relapsing-remitting multiple sclerosis for a study determining the safety and potential effectiveness of adding to disease-modifying therapy the experimental, oral therapy that may promote the repair of nerve-insulating myelin (PIPE-307). The study is sponsored by Contineum Therapeutics.Details:Background: PIPE-307 is a molecule that inhibits the muscarinic type 1 (M1) receptor. The M1 receptor is a molecule in the brain that is known to prevent the development of cells that make myelin, the insulation of nerve fibers that is damaged in MS, and the formation of myelin itself. This study will test whether adding PIPE-307 to approved disease-modifying therapies is safe and potentially effective.Eligibility: Participants should be 18 to 50 years old with a diagnosis of relapsing-remitting MS. They should have been on any MS disease-modifying therapy for six months.Participants will be randomly assigned to receive one of two doses of PIPE-307 or inactive placebo, once daily by mouth, for 26 weeks. Subjects may remain on their existing disease modifying therapy. The primary outcomes being measured are the number of people with adverse events and vision acuity (an indication of the health of the optic nerve and vision pathways in the brain). Secondary outcomes include measures of disability progression and disease activity on MRI scans.The study will include routine blood draws, neurological assessments, MRI scans, and a remote sensor worn on the ankles to assess walking (for those subjects who agree to wear the device for short intervals during the study). People will undergo a series of screening assessments to determine eligibility, and then return to the site for follow-up testing at multiple times during the treatment period.Contact: To learn more about the enrollment criteria for this study, and to find out if you are eligible to participate, please contact the site nearest you:
 
ARIZONAMegan HamiltonXenoscience, Inc.2601 N 3rd Street Suite 125Phoenix, AZ 85004602 274 9500SFLITMAN@XENOSCIENCE.COMMadison Turner, Ashely MitchellArizona Neuroscience Research, LLC3805 E Bell Rd. Suite 2400, Phoenix, AZ 85032480-210-8723madison@centerforneurologyandspine.com
ashely@centerforneurologyandspine.comCALIFORNIACasey Holden, RNREDI (Sutter Health)2850 Telegraph Avenue, Suite 110, Berkeley, CA 94705510-204-1610casey.holden@sutterhealth.orgCOLORADODevon GlazeColorado Springs Neurological Associates2312 N. Nevada Ave Suite 300Colorado Springs, CO 80907719-389-1126dglaze@csneuro.comFLORIDAKelly CalistriAqualane Clinical Research3200 Bailey Lane, Suite 180, Naples, FL 34105239-529-6780kelly@aqualaneresearch.comJodi MummertMS & Neuromuscular Center of Excellence3190 N McMullen Booth Road Suite 200, Clearwater, FL 33761(813) 431-4913jodi@gulfcoastcta.comClellia BergaminoVero Beach Neurology and Research Institute1040 37th Place Suite #201 Vero Beach FL 32960772-4492-7051 or 772-299-4304cbergamino@geodysseyrsch.comNicole DavisARS Brain and Spine1211 Dunlawton Ave. Port Orange, Fl. 32168386.204.0960 ext 632Nicole.davis@accelclinical.comGEORGIACarlyn R. Kappy, RD, LD, CCRPShepherd Center2020 Peachtree Road, NWAtlanta, GA 30309404-367-1375carlyn.kappy@shepherd.orgAndrea LevinVelocity Clinical Research6602 Waters Ave., Bldg C Savannah GA 31406912-790-4837alevin@velocityclinical.comINDIANASarah CollinsIndiana University School of Medicine Department of Neurology355 W. 16th Street, Suite 4700Indianapolis, IN 46202317-963-7315SQCollin@IU.eduKANSASLisa Schmidt, LPNUniversity of Kansas Medical Center3901 Rainbow Blvd, MS 2012, Kansas City, KS 66160913-588-3968lschmidt@kumc.eduMASSACHUSETTSJillian PellegriniNeurology Center of New England P.C.9 Payson Road, Suite 100, Foxboro, MA, 02035781-551-5812 opt 6jpellegrini@myneurodr.comMISSOURIAmber T. Smith, BS, MAWashington University School of MedicineDepartment of Neurology - John L. Trotter MS Center660 South Euclid Ave Campus Box 8111St. Louis MO, 63110314-362-3493 (p)ambertsmith@wustl.eduNEW MEXICOEmily Reese and Andrea RodriguezMS Specialty Clinic at the University of New Mexico's Health Sciences CenterNeurology Department MS Specialty Clinic
915 Camino de Salud NE, Albuquerque, NM 87131(505) 272-0959EjReese@salud.unm.eduandreRodriguez@salud.unm.eduNEW YORKAllison EmborskyDent Neurologic Institute3980 Sheridan Dr Amherst NY 14226716-558-3543
aemborsky@dentinstitute.comOKLAHOMAMicki DrakeOMRF Multiple Sclerosis Center of Excellence820 NE 15th St., Oklahoma City, OK 73104405.271.6242Micki-Drake@omrf.orgTENNESSEEKim PuccioSibyl Wray, MD Neurology, PC dba Hope Neurology2060 Lakeside Centre Way Knoxville, TN 37922865-299-5564kpuccio@hopeneuro.comTEXASZenaida HernandezBhupesh Dihenia MD PA3815 23rd Street, Lubbock, TX 79410 USA806-368-9415researchbhd@gmail.comElizabeth MartinezUniversity of Texas Health Science Center at Houston6410 Fannin, Ste 1014Houston, TX 77030(713) 704-4137elizabeth.martinez@uth.tmc.eduFahim DayaniClinical Trial Network713-484-6947fdayani@ctntexas.comWASHINGTONElisa McGeeUniversity of WashingtonMcMurray Building NWH campus, 1536 N 115th Street, Seattle, WA 98133206-598-9260emcgee@uw.eduAmelia JohnsonVirginia Mason Medical Center1100 9th Avenue Seattle, WA 98101(206) 287-6260amelia.johnson900@vmfh.orgTonya StiggerMultiCare Institute for Research & Innovation (MIRI)915 6th Ave. Suite #101, Tacoma, WA 98405253-403-1208Tonya.Stigger@multicare.orgDownload a brochure that discusses issues to think about when considering enrolling in an MS clinical trial (PDF)
 
Without participants in research studies, MS research would come to a standstill. Read more here.

How Multiple Sclerosis Changes Over Time

 

 Medically Reviewed by Christopher Melinosky, MD

 Written by WebMD Editorial Contributors

Multiple sclerosis (MS) is different for everyone who has it. The symptoms it causes and when they flare up vary not only between people but also throughout one person’s life. This means it can be hard for doctors to diagnose someone with the condition. They might say you "probably" or "possibly" have MS.

Your diagnosis is based on the symptoms you have, how and when they flare up or improve, which of your body’s functions give you trouble, and your test results. There’s no way to predict how your condition will change throughout your life. It may take time, but as your doctor gets more clues about the type of MS you have, you can have a clearer idea of how it will affect you in the coming years.

The way the disease changes and gets worse is different for each of the three types of MS:

• Relapsing-remitting MS: People with this type have attacks when their symptoms get worse, called relapses, followed by full, partial, or no recovery. These flares seem to change over several days to weeks. Recovery from an attack takes weeks, sometimes months, but symptoms don’t get worse during this time. Most people have this type when they’re first diagnosed with MS.
• Secondary-progressive MS: People who get this type usually start with relapsing-remitting MS. Over time, symptoms stop coming and going and begin getting steadily worse. The change may happen shortly after MS symptoms appear, or it may take years or decades.
• Primary-progressive MS: In this type, symptoms gradually get worse without any obvious relapses or remissions. About 15% of all people with MS have this form, but it’s the most common type for people diagnosed after age 40.

Depression can be common with MS

 

Symptoms to watch out for

There’s a difference between depression and the sadness, grief, and other painful life events that everyone goes through in life. As a whole, most people with MS will experience grief, loss, and sadness due to having this disease in and of itself. For some, this can be considered a mild, tolerable form of depression and is considered quite common. For others, it can escalate into something more serious.

Depressive episodes can certainly ebb and flow when living with MS and/or other chronic illnesses. It’s normal, and everyone reacts differently to such feelings and emotions. However, if you find your thoughts, feelings, and behavior changes lasting beyond several weeks, this could be a warning sign.¹

Symptoms of depression might include:

• Lingering sadness, agitation, and irritability
• Loss of interest in activities
• Changes in appetite
• Sleep hygiene changes/insomnia
• Increased fatigue
• Feelings of worthlessness or guilt
• Decrease in focus or concentration
• Thoughts of self-harm or suicide

You're not alone

It’s important to pay attention to your mood changes and recognize when/if it’s time to seek help. Sometimes patients find cognitive behavioral therapy (CBT) or medication to be helpful. Creative expression, therapeutic outlets, interaction with others, and engaging in some form of physical activity can be healthy and helpful as well. Find something… whatever works best for you.

Lastly, always remember you’re not alone. There are many others who might be going through the same thing as you. They can relate and might be able to offer comfort. Support is out there!

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Advances in Treatment of Multiple Sclerosis

 

Drugs May Help Rebuild Myelin

Two drugs, metformin (Fortamet, Glucophage, Glumetza, Riomet) and clemastine (Dayhist, Tavist), may help rebuild your myelin. Usually, metformin treats diabetes and clemastine helps with hay fever. Researchers found metformin can help myelin-making cells repair it better. Experts found clemastine helped with the speed of messages from your eye to your brain. Animal studies showed metformin can improve the effect of clemastine.

More research is needed about the effects on humans.

Pioglitazone May Prevent Myelin Damage

Experts are doing clinical trials with pioglitazone (Actos), a diabetes medication, in people with progressive MS. They want to see whether the drug can target immune system attacks on myelin. Pioglitazone may be a useful therapy to protect nerve fibers from more damage and even repair damage to myelin.

BTK Blockers May Lessen Nerve Damage

Bruton’s tyrosine kinase (BTK) plays a role in the survival of B cells, white blood cells that make antibodies. Some B cells are linked to MS relapses and progression because they attack myelin. BTK inhibitors (BTKis) target B cells that can do damage while leaving useful B cells alone. BTKis were first used to treat cancer. Now scientists are studying some BTKis – evobrutinib, fenebrutinib, orelabrutinib, and tolebrutinib – in clinical trials to find out how effective they are against MS.

ATA188 Targets EBV, May Help MS 

This therapy targets Epstein-Barr virus (EBV), which is believed to play a role in how likely you are to get MS. ATA188 involves T cells (white blood cells in the immune system) that target and kill cells infected with EBV. Experts are studying the proper dosages, safety, and success of this intravenous (IV) infusion and how it can help treat progressive MS. 

Ibudilast Can Slow Brain Shrinkage

Ibudilast (MN-166) is an anti-inflammatory drug that lowers the action of an enzyme called phosphodiesterase. Blocking the enzyme can lessen inflammation and promote nerve growth. Ibudilast can’t stop new MS lesions. But it can slow brain shrinkage and stop some immune system actions that can lead to nerve damage. Researchers also found that ibudilast appears to help treat slowly evolving lesions (SELs) in people with progressive MS.

Stem Cell Therapy for Harmful Cells

This treatment uses or targets stem cells, which are cells that can turn into different types of specific cells all over your body. They can help your body repair itself. One form of stem cell therapy is hematopoietic stem cell transplantation (aHSCT). Experts use this to reset your immune system through chemotherapy. If you have MS, this will get rid of harmful cells that cause damage and swap them with healthy immune cells. 

DMTs That Can Change the Course of MS

Disease-modifying therapies (DMTs) can help control your MS symptoms. The FDA has approved different types of medication to treat and manage MS:

• Ocrelizumab (Ocrevus), ofatumumab (Kesimpta), and ublituximab-xiiy (Briumvi) target CD20, a protein on the surface of B cells. These B cells are white blood cells that have been shown to play a role in MS.
• Diroximel fumarate (Vumerity) lessens inflammation and stops nerve damage that may cause MS symptoms.
• Fingolimod (Gilenya) reduces the MS relapse rate in adults and children. It’s the first FDA-approved MS drug for kids.

Other DMTs That Can Change the Course of MS

• Ozanimod (Zeposia) can help with clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS.
• Ponesimod (Ponvory) can lower the chance of MS symptoms coming back by more than 30%.
• Cladribine (Mavenclad) and siponimod (Mayzent) are other treatments that can lower your relapse rate if you have MS. They stop certain cells of the immune system from causing nerve damage.

Cladribine for Other Forms of MS

As mentioned, this drug already helps people with relapsing-remitting MS. The first trial of its kind is studying whether cladribine can help more advanced progressive MS. Experts are hopeful because it’s one of the few DMTs that can get inside your brain and spinal cord. That's why it’s so helpful for relapsing MS.

Cholesterol Drugs May Help With MS

Simvastatin (Flolipid, Zocor) is a statin doctors prescribe to treat high cholesterol. It may also help slow down secondary progressive MS. Some studies show that higher cholesterol levels are linked to worsened MS. Because of this, experts thought simvastatin might slow down MS progression if it lowers your cholesterol. But a more recent study found that the drug directly slows down the progression of MS, even if it doesn’t help your cholesterol levels.

https://www.webmd.com/multiple-sclerosis/ss/cm/slideshow-multiple-sclerosis-advances-treatment?ecd=wnl_mls_042624&ctr=wnl-mls-042624_lead_cta&mb=q80%2f%40kIeuyYKtyaYzOxdbc6RVoMqf%400VkpmvpK5yEEQ%3d

 

Strange MS Symptoms

 Here are some discussions of strange and unique MS symptoms:

https://multiplesclerosis.net/living-with-ms/strange-symptoms-experience

https://msfocus.org/Magazine/Magazine-Items/Posted/Understanding-the-Rarer-Symptoms-of-Multiple-Scler

https://www.mymsteam.com/resources/unusual-sensations-and-ms-causes-and-when-to-worry

https://legacyneuro.com/toothache-trigeminal-neuralgia/

https://www.upstate.edu/whatsup/2013/0625-that-painful-toothache-may-be-trigeminal-neuralgia-heres-how-to-treat-it.php

https://www.webmd.com/multiple-sclerosis/ss/slideshow-unusual-symptoms-ms

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313873/

https://mail.google.com/mail/u/0/#inbox/FMfcgzGxSlMCkJgTGZtBswnjjpDDZcQb

Disparities in Pregnancy Experiences Found Among Black, Hispanic/Latinx and White Women with MS

 Researchers examined medical records of women with MS in the U.S. and their pregnancy outcomes, comparing those of Black, Hispanic/Latinx, and white people. They reported that those identifying as Black or Hispanic/Latinx tended to enter pregnancy with higher levels of MS disability and often with fewer health care resources. There were also differences in types of delivery, birthweights, and socioeconomic factors.
 
Why Does This Matter? This study adds to the growing awareness of health disparities and can inform ongoing efforts to improve care for everyone living with MS.
 
Background: MS is highly individualized, and disease characteristics and a treatment plan are significant considerations in family planning and pregnancies. These investigators wanted to understand how healthcare inequities may impact the pregnancy outcomes of Black and Hispanic/Latinex women. Previous studies suggest that prenatal care is especially important for Black and Hispanic/Latinx women because they tend to have higher risks of high blood pressure, diabetes and other disorders that may complicate their pregnancies.
 
Study Details: To better understand differences among women with MS and their pregnancy experiences, Dr. Riley Bove (University of California, San Francisco - UCSF), a National MS Society Harry Weaver Scholar, and collaborators examined medical records from 9 MS centers in the U.S. They looked for pregnancy and delivery information of women with MS or CIS (a single neurological event that indicates early MS) between 2010 and 2021. They analyzed 294 pregnancies that resulted in live births.
 
Results: Some differences they found included:

• Black and Hispanic/Latinx women tended to be younger than white women when they became pregnant, and they had higher levels of MS disability when they became pregnant.
• More white women had private insurance, and more received an ultrasound exam at 14 weeks of pregnancy.
• Black women had the highest rates of emergency cesarean deliveries, and Hispanic/Latinx women had the fewest delivery complications. Babies’ birth weights of both tended to be lower than those of white women.

 
Comment: The authors suggest that some reasons for the differences may include availability of transportation, types of insurance, social support, and access to prenatal care. Studies like these can inform ongoing efforts to improve care for everyone living with MS.

Why Do Women Have More Autoimmune Diseases? Study Points to X Chromosome

 

By Carl Zimmer

Feb. 1, 2024

Women are much more likely than men to have their immune system turn against them, resulting in an array of so-called autoimmune diseases, like lupus and multiple sclerosis. A study published on Thursday offers an explanation rooted in the X chromosome.

The research, published in the journal Cell, suggests that a special set of molecules that act on the extra X chromosome carried by women can sometimes confuse the immune system.

Independent experts said that the molecules are unlikely to be the sole reason autoimmune disease skews female. But if the results hold up in further experiments, it might be possible to base new treatments on these molecules, rather than on the current drugs that blunt the entire immune system.

“Maybe that’s a better strategy,” said Dr. Howard Chang, a geneticist and dermatologist at Stanford who led the new study.

Male and female embryos carry 22 identical pairs of chromosomes. The 23rd pair is different: Females carry two Xs, while males carry an X and a Y, which lead to the development of male sex organs.

Each chromosome holds genes that, when “switched on,” produce proteins to do work inside of cells. You might expect that women, with two copies of X, would make twice as many X proteins as men do. Instead, they produce about the same level. That’s because one of the two X chromosomes is silenced.

A molecule called Xist clings to the second X chromosome “like Velcro,” Dr. Chang said. As hundreds of Xist molecules wrap themselves around the X chromosome, they completely shut it down.

Keeping one X silent is crucial to women’s health. If a gene on the second X chromosome escapes Xist’s control, it will result in an excess supply of proteins, some of which could be toxic.

In 2015, it occurred to Dr. Chang that the silencing itself might also have a downside. His epiphany occurred while he was preparing to take his medical board exams to renew his license as a dermatologist.

As part of his studies, Dr. Chang had to brush up on autoimmune diseases, memorizing the names of human proteins that can be targeted by a misdirected immune system. When he looked at the list, he was surprised to see some familiar names.

When Dr. Chang isn’t working as a dermatologist, he researches the X chromosome in his lab. He noticed that many of the proteins involved in autoimmune diseases also helped Xist silence the X chromosome.

Maybe, Dr. Chang thought, that was no coincidence.

The new study emerged from years of research testing his hunch that Xist molecules could cause autoimmune disease. He and his colleagues studied a strain of mice in which the females are at high risk of the autoimmune disease lupus, while the males never develop severe cases.

The researchers genetically engineered the male mice so that they, like the females, produced Xist. “Once the male mice express Xist, they get much worse levels of immune disease,” Dr. Chang said.

The researchers also found that people with lupus or two other autoimmune disorders had high levels of antibodies to Xist-related proteins in their blood.