treatment

Advertising for stem cell therapies not supported by clinical research — often made directly to patients and sometimes promoted as a "cure" for diseases like multiple sclerosis or Parkinson's — is a growing problem that needs to be addressed and regulated, a team of leading experts say, calling such "stem cell tourism" potentially unsafe. Stem cell tourism is the unflattering name given to the practice of encouraging patients to travel outside their home country to undergo such treatment, typicaly at a private clinic. The article, titled "Marketing of unproven stem cell–based interventions: A call to action" and recently published in the journal Science Translational Medicine, was co-authored by scientists with universities and hospitals in the U.S., Canada, U.K., Belgium, Italy, Japan, and Australia. It focuses on the global problem of the commercial promotion of stem cell therapies and ongoing resistance to regulatory efforts. Its authors suggest that a coordinated approach, at national and international levels, be focused on "engagement, harmonization, and enforcement in order to reduce risks associated with direct-to-consumer marketing of unproven stem cell treatments." Treatments involving stem cell transplants are now being offered by hundreds of medical institutions worldwide, claiming efficacy in repairing tissue damaged by degenerative disorders like MS, even though those claim often lack or are supported by little evidence . They also noted that the continued availability of these treatments undermines the development of rigorously tested therapies, and potentially can endanger a patient's life. The researchers emphasize that tighter regulations on stem cell therapy advertising are needed, especially regarding potential clinical benefits. They support the establishment of international regulatory standards for the manufacture and testing of human cell and tissue-based therapies. "Many patients feel that potential cures are being held back by red tape and lengthy approval processes. Although this can be frustrating, these procedures are there to protect patients from undergoing needless treatments that could put their lives at risk," Sarah Chan, a University of Edinburgh Chancellor’s Fellow and report co-author, said in a news release. Chan and her colleagues are also calling for the World Health Organization to offer guidance on responsible clinical use of cells and tissues, as it does for medicines and medical devices. "Stem cell therapies hold a lot of promise," Chan said, "but we need rigorous clinical trials and regulatory processes to determine whether a proposed treatment is safe, effective and better than existing treatments." According to the release, the report and its recommendations followed the death of two children at a German clinic in 2010. The clinic has since been shut down. Certain stem cell therapies — mostly involving blood and skin stem cells – have undergone rigorous testing in clinical trials, the researchers noted. A number of these resulted in aproved treatments for certain blood cancers, and to grow skin grafts for patients with severe burns. Information about the current status of stem cell research and potential uses of stem cell therapies is available on the website EuroStemCell.

B-cells of patients with relapsing-remitting multiple sclerosis (RRMS) secrete substances that are toxic to both neurons and neuron-protecting myelin-forming cells, causing both kinds to die, according to a study. Despite analyses of numerous inflammatory and other factors believed to drive MS processes, researchers were unable to identify the molecules that are toxic, however. Dr. Robert Lisak of Wayne State University in Detroit, Dr. Amit Bar-Or of McGill University in Montreal and their teams are now working on identifying the factor, and learning if the process is also involved in progressive MS. Their study, “B-cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro,” was published in the Journal of Neuroimmunology. It demonstrated that B-cells gathered from the blood of RRMS patients killed lab-grown neurons and oligodendrocyte cells, which form myelin, a protecting coating for nerve cells. Deterioration of the myelin coating and the death of neurons are hallmarks of MS. An earlier study the team conducted indicated that B-cells from MS patients could kill oligodendrocytes. But since the experiments involved only three patients and three controls, the team scaled up their experiments to include 13 patients and an equal number of controls. Both rat and human neurons died when mixed with MS-derived B-cells. In contrast, B-cells from healthy people had little or no impact on the survival of the brain cells. Researchers also discovered that the secreted toxic molecules had no impact on other types of central nervous system cells — astrocytes and microglia. The toxins killed only neurons and myelin-producing cells. The B-cells triggered a process called apoptosis, or programmed cell death, researchers said. This is basically a suicide program. It tells a cell to die when exposed to stressful factors or toxins. The process differs from cell disintegration. Despite thoroughly screening about 40 inflammation-related substances, researchers were unable to identify any factors that caused the cells to die. The National MS Society and the Research Foundation of the MS Society of Canada funded the research, which the U.S. society highlighted in a news release. In the newest phase of the study, researchers will try to learn more about the processes underlying neuron and myelin-related cell deaths and identify the factors responsible. In addition to testing B-cells from progressive MS patients, the team will examine patients with other autoimmune conditions to see if the process is unique to MS or not. Researchers increasingly realize that B-cells are important to MS processes. This observation was underscored by U.S. regulators' approval of the B-cell depleting therapy Ocrevus (ocrelizumab) at treatment for both relapsing and primary progressive MS.

I’ve been considering writing about the fun, fun world of catheters. As this column is morphing into some sort of diary, let’s deal with this week’s medical procedural drama. Welcome to UTI (urinary tract infection) week. Anyone who uses a catheter is prone to a higher incidence of…

Genentech shared new insights into the workings of Ocrevus (ocrelizumab) and its effectiveness in reducing disease activity and slowing progression in relapsing and primary progressive multiple sclerosis (MS) at the recent 3rd Congress of the European Academy of Neurology (EAN). The new findings, previously reported here, built on analyses of information gathered during the three Phase 3 clinical trials assessing Ocrevus' safety and efficacy, as well as through monitoring patients in extension studies. The studies showed that nearly 40 percent of Ocrevus-treated relapsing patients and nearly 30 percent of primary progressive patients achieved NEPAD during the Phase 3 trials. In contrast, only 21.5 percent of those treated with Rebif and 9.4 percent receiving placebo achieved NEPAD — figures that demonstrate Ocrevus’ impact on patients’ lives, as well as Ocrevus’ ability to slow the decline in walking ability and other types of disabilities are comparable between patients with relapsing and primary progressive disease — data that demonstrate that the treatment acts on disease mechanisms that drive disability in both disease forms. How these effects play out in the long-term is the subject of ongoing research, as Genentech continues to follow these patients in an extension study. In addition, Ocrevus' prescription label strongly advises against pregnancy while on the treatment. Despite precautions, some women became pregnant during the trials. One of the meeting presentations narrated outcomes of these pregnancies; one healthy baby born at term and two ongoing pregnancies in women exposed to the drug. But while Genentech monitors women who become pregnant while on Ocrevus, the number of reported pregnancies is too small to draw conclusions about the treatment’s safety in pregnancy, and researchers do not know if Ocrevus also depletes B-cells in the fetus or in the baby born to a treated woman.

New analyses of how Merck’s Mavenclad (cladribine tablets) act to treat relapsing multiple sclerosis (MS) give researchers an entirely new picture of immune processes leading to the disease. Data showed that the drug lowers both immune B-cells and, to a lesser degree, T-cells. But the numbers of both cell…

I’ve done it! I made the treatment switch that so many people with multiple sclerosis are talking about: I said goodbye to Tysabri (natalizumab) and am now on Ocrevus (ocrelizumab) as my disease-modifying therapy (DMT). I went through 56 monthly infusions (or maybe more, I’ve…

MS patients who start treatment at a younger age, and whose condition requires hospitalization, are more likely to stop treatment, a Canadian study reports. The research, published in the journal Dovepress, dealt with the main reasons Canadian patients quit first-line injected disease-modifying therapies, or DMTs. It was titled “Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort.” DMTs can reduce MS activity, but patients must stick with them in order for them to be effective. “There is currently a paucity of clinical trial data on what happens to individuals when they discontinue DMT," the researchers wrote. "However, recent preliminary evidence from observational studies suggest increased relapses and disability in those who discontinue DMT." Researchers sought to identify MS patients at higher risk of discontinuing treatment. They looked at Manitoba Province's medical database to identify the types of drugs MS patients were taking, and for how long. The analysis covered 721 patients who received injected beta-interferons or Copaxone between 1996 and 2011, and whom doctors followed for at least a year. Teva manufactures Copaxone, whose generic name is glatiramer acetate. The mean age of the patients in the study was 37.6 years, and 74.2 percent were women. Researchers defined a discontinuation of a DMT as a 90-day or longer gap in treatment. A third of the patients were treated with beta-interferon-1b, either Bayer HealthCare's Betaferon/Betaseron or Novartis' Extavia. It was the first such therapy available in Manitoba. Twenty-three percent of patients received beta-interferon-1a, either Biogen's Avonex or Merck's Rebif. And 21 percent received Copaxone. The median time before a patient discontinued a DMT was 4.2 years. Although 62.6 percent of patients discontinued treatment at some point, 57.4 percent either reinitiated it or switched to a different DMT. Patients who were on DMT at least a year were more likely to stay with it than those who stopped in the first year. Importantly, patients who started a DMT at a younger age were more likely to stop taking it than older patients. “Our results are also consistent with previous work examining persistence for other chronic medication classes, including statins, antihypertensives, bisphosphonates, and oral antidiabetic agents, where the risk for discontinuing drugs declined in a linear fashion with age,” the researchers wrote. The team also found that 16 percent of patients had to be hospitalized overnight, with 3 percent of the cases due to MS-related complications. And these hospitalized patients were more likely to stop their DMT treatment earlier, the researchers said. Summing up, the team said: "Subjects who were younger when starting a DMT, had prior MS-related hospitalizations, were more recently diagnosed with MS, or had a greater lag time between their MS diagnosis and DMT initiation were more likely to discontinue therapy." Although "not all of the factors identified with discontinuing DMT" can be modified, "they may help practitioners enhance MS care by identifying individuals who may be at particular risk for DMT discontinuation," the researchers concluded.

The over-the-counter antioxidant lipoic acid slowed brain deterioration in patients with secondary progressive multiple sclerosis (SPMS), according to a pilot study. An Oregon Health & Science University research team conducted the study, “Lipoic acid in secondary progressive MS.” It was published in the journal Neuroimmunology and Neuroinflammation. A hallmark…

Innate Immunotherapeutics' MIS416 has failed to help secondary progressive multiple sclerosis (SPMS) patients in a Phase 2 clinical trial. The company said it will continue testing the therapy, made up of natural compounds, to see if it can benefit any MS subgroups. Trial participants who received MIS416 had no meaningful improvements in neuromuscular function or the outcome of their disease, compared with those who took received a placebo. “It is disappointing that these results don’t show benefit for people with secondary progressive MS, for whom there are few treatment options,” Dr. Bruce Bebo, executive vice president of research at the National MS Society, said in a news release. Scientists hoped the injected therapy would modulate the activity of immune cells that affect the protective myelin coating around nerve cells, decreasing the inflammation and brain tissue damage associated with MS. Deterioration of the coating is a hallmark of the disease. The one-year trial (NCT02228213) tested the safety and effectiveness of MIS416 on 93 patients with SPMS in Australia and New Zealand. The patients randomly received MIS416 or a placebo once a week. There were no differences in the groups' scores on a disability index — the expanded disability status scale — or in brain volume changes detected by magnetic resonance imaging. In addition, there were no differences between in disease outcomes that patients reported. The self-reported barometers included the Multiple Sclerosis Impact Scale, the Neurological Fatigue Index, and the Brief Pain Inventory. "I am extremely disappointed by this outcome," Professor Pam McCombe, a principal trial investigator, said in a company press release. "Looking for measurable changes in patients with progressive MS using the assessment tools currently at our disposal is frustrating and complicated. We were hopeful that MIS416 would be an option to treat this group of patients who currently do not have effective treatment options." In addition to MIS416 failing to be effective, the group who received it had more treatment-related adverse events than the placebo group. The events were mainly related to the first dose, Innate said. The main problems were fever, chills, and muscle weakness. The company has been providing MIS416 to Australian MS patients under a compassionate use program. It said it will continue evaluating the safety and tolerability of the drug to see if it helps any subgroups of patients. Those findings will determine the future of the compassionate use program, it said. “These results are a shock, and definitely not what we were expecting based on our previous clinical experience with MIS416 and the reporting of treatment benefits we have received from many compassionate use patients over an extensive eight-year period," said Simon Wilkinson, Innate Immunotherapeutics' chief executive officer. "These data will be as distressing to them as they will be for all the stakeholders who were relying on the outcome of this study."

So, I recently signed up to join a new and much closer exercise class. The previous drive of nearly an hour each way had proved to be beyond my range. Actually doing exercise when I got there seemed bonkers! But I haven’t been there as of yet ― my…

It’s been a little over six months since I completed Round 1 of my Lemtrada infusions, so it’s time again to ask myself, “How am I doing?” The answer: I’m not sure. For many years, my brain MRI has remained unchanged. I can’t remember the last time…

The multiple sclerosis therapy Tysabri could trigger melanoma, the Southern Network on Adverse Reactions (SONAR) has warned. Although its investigation failed to demonstrate that melanoma is more common among Tysabri-treated MS patients than in the general population, unusual features among the patients raise concerns about a possible link, the organization said. Contending that current monitoring efforts are inadequate, it suggested improvements that could generate a better understanding of the relationship between Tysabri treatment and cancer. The organization's report, published in the journal Cancer Medicine, was titled “Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions, also known as SONAR." SONAR is an organization that was formed in the Southern United States in 2010 to investigate adverse drug reactions that regulators might not be aware of. Its goal is to reduce the time it takes between detecting an adverse reaction and have regulators act on it. A case that a SONAR investigator came across led to the group investigating possible links between Tysabri and melanoma. A 43-year-old woman developed melanoma in her urethra, the tubing that drains urine from the bladder, after being treated with Tysabri for about two years. Melanoma is most often a skin cancer that is related to sun exposure, but the woman had no skin lesions. After extensive surgery, she relapsed and died when the cancer spread to other parts of her body. She had declined anti-cancer treatment. The case prompt SONAR to look for similar cases. Its investigators found seven studies that involved Tysabri-treated MS patients developing melanoma. In addition, they looked through the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) and the Tysabri Safety Surveillance Program. The surveillance program is part of the Tysabri Outcomes Unified Commitment to Health (TOUCH) database run by Tysabri's developer, Biogen, The research team found 137 cases in the FAERS database through April 1, 2014. The patients' average age was 45. Seventeen percent of the group developed tumors in locations not exposed to the sun, and nine died. The researchers said the database contained only about half the information it should have, such as tumor site, patients' family history of cancer, and earlier immunosuppressive treatment. Fifteen percent of the cases in the FAERS database were based entirely on information from the TOUCH database. Seventy-three percent were cases initially reported to FAERS but with TOUCH information added. Thirteen percent of the FAERS cases contained no additional information. Importantly, there was even less patient information in the TOUCH database than in the FAERS database. Out of eight items researchers believe a database should contain, TOUCH had information on two, on average. “The existence of the TOUCH Safety Surveillance Program, an FDA-mandated program, did not improve melanoma reporting,” the team wrote. This shortage of data stymies research into possible links between Tysabri treatment and melanoma, the researchers said. As an example, although the death rates in the databases were low, there was no information about survival in many cases, which could lead to flawed survival estimates. The investigation noted that patients received a wide range of Tysabri doses before they were diagnosed with melanoma. While some received only one or a few injections, others had been treated for a long time. These observations do not seem to support a link between Tysabri and melanoma, the team said. “A longer therapy duration would be expected if natalizumab caused melanoma via an immunologic pathway, unless existing nevi [lesions of the skin or mucus tissue] were already premalignant lesions,” the researchers wrote. But other information the team found seemed to suggest a Tysabri-melanoma link. For example, the average age of melanoma patients was much lower than that reported in the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. The average age in the institute's database is 63, compared with 45 in the FAERS database and 41 in cases in academic journals. In addition, many patients developed tumors in unusual places not exposed to sunlight. Finally, the low melanoma death rate in Tysabri-treated patients differed from that seen in the general population. All these factors suggest that melanoma after Tysabri treatment could differ from other types of melanoma, the researchers argued. While the molecular workings of Tysabri might promote melanoma growth, studies so far have not found a relationship between the drug and this cancer. In fact, some studies suggest that MS patients, in general, have a lower risk of melanoma than others. The team said more information on patients could give researchers a better understanding of the potential relationship between Tysabri and melanoma. The implication was that the standard of reporting in the FAERS and TOUCH databases could improve. To minimize the risk of patients who receive Tysabri developing melanoma, the researchers offered a number of suggestions for IV centers, physicians, patients, and educational programs. For instance, they suggested that all patients should have a skin examination before the start of treatment, and regular physical and skin exams while receiving Tysabri. While noting that risk of infection and the development of tumors can occur with all immunosuppressive treatments, the team said more studies are needed to explore the risk of Tysabri-treated patients developing melanoma.

TG Therapeutics’ investigational treatment — ublituximab (TG-1101) — led to a near total depletion of B-cells in patients with relapsing forms of multiple sclerosis (MS) taking part in an ongoing Phase 2 trial, the company recently announced. In addition, the company said that ublituximab had an infusion time as short as one hour, without excessive side…

During a routine exam with my neurologist recently, I asked her a question I’d never thought to ask before: “Why do you order regular MRIs of my brain, but not of my spine?” Interestingly, within a few days of my exam, a Harvard Med School study was…

Merck’s cladribine tablets are now just one step away from obtaining European Union approval as a relapsing multiple sclerosis treatment. The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended that the European Commission approve the tablets. “The positive opinion from the CHMP [the committee] is an extraordinary…

A recent study has found Tysabri (natalizumab) treatment for two years to be efficient and safe in Japanese patients with relapsing-remitting multiple sclerosis (RRMS). The study, “Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial,” appeared in the journal…

In case you missed them, here are some news stories that appeared in MS News Today that caught my eye over the past week. **** Harvard Study Finds No Link Between Clinical Exams and MRIs in Some MS Patients I’m really not surprised…

Lemtrada (alemtuzumab) may be an effective option for relapsing-remitting multiple sclerosis (RRMS) patients withdrawing from prior treatment with Tysabri (natalizumab), an Italian study shows. The study, “High-Risk PML Patients Switching from Natalizumab to Alemtuzumab: an Observational Study,” appeared in the journal Neurology and Therapy. Tysabri, an antibody with…

Ocrevus (ocrelizumab) significantly reduces disease activity and disability progression in patients with relapsing multiple sclerosis (MS) and primary progressive MS (PPMS), according to results of post-hoc analyses of Genentech’s Phase 3 clinical trial program assessing the drug.

Several months ago, I wrote a column about Andrew Barclay. Barclay died in an assisted suicide in December. He’d had multiple sclerosis for many years. Colin Campbell is a 56-year-old MS patient who lives in Inverness, Scotland. He also wanted to die. In fact, he was scheduled…

Shared decision-making between patients and their doctors and healthcare providers was considered a critical step in the process of treating multiple sclerosis (MS), according to an article published in the journal Practical Neurology. The article “Shared Decision-making in Multiple Sclerosis Management” was written by Amy Perrin Ross, a board-certified…

Multiple sclerosis patients taking Tecfidera, or dimethyl fumarate, were more productive at work than those on Copaxone or beta-interferon therapies, according to a study. Tecfidera also increased patients’ quality of life, researchers said. The study covered patients with relapsing-remitting multiple sclerosis, or RRMS. The four beta-interferon treatments were Avonex, Betaseron, Rebif,…

Stephen L. Hauser, MD, director of the University of California, San Francisco (UCSF)‘s Weill Institute for Neurosciences, has been awarded the 2017 Taubman Prize for Excellence in Translational Medical Research. Recognized for scientific work that challenged the way multiple sclerosis (MS) is regarded, Hauser’s discoveries have opened new therapeutic…

AXIM Biotechnologies has secured an additional $4 million in institutional financing to advance clinical trials of its cannabinoid therapies for multiple sclerosis (MS) and irritable bowel syndrome. Some of the trials involve a chewing-gum therapy delivery system. The financing will let the company continue developing a patented chewing-gum-delivered therapy for pain and spasticity. AXIM…

The U.S. Food and Drug Administration (FDA) has expanded approval of Dysport (abobotulinumtoxinA) for treatment of spasticity in adults, a condition that affects many people in the United States, including multiple sclerosis patients. The decision was based on Dysport’s supplemental Biologics License Application (sBLA)…

Researchers managed to change the immune system — replacing inflammation with immune tolerance — in a mouse model of multiple sclerosis (MS) using so-called quantum dots, or nano-sized particles carrying pieces of myelin. Experiments with this advanced technological solution may help researchers design MS therapies that are based on promoting regulatory T-cells rather…

At times it can be difficult to know whether the cognitive issues I experience are the result of aging or multiple sclerosis. According to The National Multiple Sclerosis Society (NMSS) more than half of those living with MS develop problems with cognition, and in some cases…

In case you missed them, here are some news stories that appeared in MS News Today that caught my eye over the past week. Ocrevus Phase 3 Trial Will Explore How Treatment Works by Viewing Changes in Spinal Fluid This new clinical study will try to…

Have you ever hit a brick wall trying to self-inject? I have. It was with Avonex, the first DMD that I used. To make a long story short, after a couple of years of poking myself in the thigh muscle, I just couldn’t do it anymore. That’s…

The British fundraising group The October Club and The MS Trust, a U.K. multiple sclerosis research and support organization, have announced an ambitious plan to potentially help thousands of advanced MS patients in need of services. Composed of people working in the financial equity industry in London, The October Club raises money for a different charity each year through…