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Kezar Life Sciences announced that it is planning to move ahead with clinical testing of KZR-616, a potential treatment for multiple sclerosis (MS) and other autoimmune diseases and inflammatory disorders. The company recently concluded a Phase 1 safety study of the treatment, and raised $50 million in investment funding to support its development. KZR-616 is a first-in-class selective immunoproteasome inhibitor, meaning it works by blocking abnormal protein degradation. Cells eliminate proteins by sending them to a specialized cell compartment known as the proteasome. In immune cells, the proteasome is called immunoproteasome, and it regulates several selective inhibitors and participates in the regulation of the immune response associated with inflammatory diseases such as MS, rheumatoid arthritis, Crohn's disease, and lupus. "We are pleased with the results of our healthy volunteer study, and grateful for the support of such an excellent group of investors to finance our upcoming clinical trials," John Fowler, Kezar Life Sciences’ CEO, said in a news release. "The strong demand for this financing reflects growing excitement for the potential of immunoproteasome inhibition in treating autoimmune disorders and recognizes the clear leadership position enjoyed by Kezar." The Phase 1 trial enrolled 82 healthy subjects, who were assigned to receive either KZR-616 or placebo. In total, 61 volunteers were given KZR-616 as single or multiple doses at varying dose levels to identify the optimal dose for both tolerability and proteasome inhibition. Results will be presented at the American College of Rheumatology's Annual Meeting to be held in San Diego in November. "These initial clinical trial results demonstrate that KZR-616 is achieving the desired levels of immunoproteasome inhibition that correlate with anti-inflammatory activity seen in laboratory models,” said Christopher Kirk, PhD, company president and CSO. “By selectively targeting the immunoproteasome, we believe we can avoid the toxicities associated with dual proteasome inhibitors like Velcade and Kyprolis." The Series B financing round was led by Cormorant Asset Management and Morningside Venture and raised $50 million to support the development of KZR-616. Kezar announced it has the support of new investors, including Cowen Healthcare Investments, Pappas Ventures, Qiming Venture Partners, and Bay City Capital. "Cormorant is pleased to support Kezar as it enters an exciting series of patient studies, the first ever with a selective immunoproteasome inhibitor," said Bihua Chen, founder of Cormorant Asset Management. "While much work remains, I believe KZR-616 has the potential to be a transformative treatment in autoimmunity."

A cell therapy intended to boost myelin regeneration — Q-Cells by Q Therapeutics — has received a green light from the U.S. Food and Drug Administration to proceed with a clinical trial in patients with transverse myelitis (TM), a disease that like multiple sclerosis is characterized by myelin damage. FDA approval of the company’s Investigational New…

Canadian oilman Hank Swartout made a fortune as longtime founder and CEO of Precision Drilling. The Calgary native mortgaged his house to start the company, which by the time he left in 2009 had annual sales of $7 billion. But an early diagnosis of multiple sclerosis (MS) at the age…

Eli Lilly and Nektar Therapeutics have established a development and commercial agreement for the investigational T-cell stimulator therapy NKTR-358 for the treatment of autoimmune disorders, including multiple sclerosis. NKTR-358, discovered and initially developed by Nektar, has the potential to modulate immune system responses to re-establish an immune balance in patients with autoimmune disorders. The treatment targets the interleukin 2 receptor complex (IL-2R) that is expressed on the surface of a subset of immune cells called regulatory T-cells, or Tregs. NKTR-358 activity stimulates the proliferation of Tregs, which in turn will regulate the activity of other immune cells that are uncontrolled and are responsible for the underlying mechanisms of autoimmune disorders. "We look forward to working with Nektar to study this novel approach to treating a number of autoimmune conditions," Thomas F. Bumol, PhD, senior vice president of biotechnology and immunology research at Eli Lilly, said in a press release. "NKTR-358 is an exciting addition to our immunology portfolio and reinforces Lilly's commitment to sustain a flow of innovative medicines in our pipeline." Bumol added. Under the agreement, Lilly and Nektar will continue to jointly develop NKTR-358. Nektar will be responsible for completing the ongoing Phase 1 clinical study; and Phase 2 clinical development costs will be shared by the two companies, with Lilly covering 75 percent of the costs and Nektar the remaining 25 percent. Nektar will have the option to take part of the Phase 3 development of NKTR-358 on an indication-by-indication basis. "We are very pleased to enter into this collaboration with Lilly as they have strong expertise in immunology and a successful track record in bringing novel therapies to market," said Howard W. Robin, president and CEO of Nektar. "Importantly, this agreement enables the broad development of NKTR-358 in multiple autoimmune conditions in order to achieve its full potential as a first-in-class resolution therapeutic." Based on the announced agreement, Lilly will pay an initial amount of $150 million to Nektar, which will also be eligible to receive up to $250 million from additional development and regulatory milestones. In the future, Nektar may also receive royalties from the product depending on its investment in NKTR-358’s Phase 3 development and future product sales. Lilly will cover all costs of global marketing of NKTR-358, and Nektar will have an option to co-promote the drug in the United States.

A new study draws a reverse link between the number of MRI scans of multiple sclerosis patients who are on interferon-beta 1a and doctors declaring there is evidence of the patients’ disease worsening. When doctors looked at one scan, rather than multiple ones, they were more likely to say that…

According to a study by researchers at Cleveland's Case Western Reserve University School of Medicine, pre-existing inflammatory diseases affecting the central nervous system make mesenchymal stem cells less effective in treating multiple sclerosis. The study notes that MSCs potentially produce several signaling proteins that can regulate immune system responses as well as help tissue regenerate. Preclinical studies have shown that this can reduce brain inflammation while improving neural repair in animal models of experimental autoimmune encephalomyelitis -- an animal version of MS that is often used in laboratory studies, since it resembles the inflammation and neuronal damage seen in MS patients. Given the need for effective new MS therapies, the results will help MSCs to advance to human clinical trials. So far, results have reported good safety data, though such therapies have failed to demonstrate therapeutic efficacy. Most such trials so far have used stem cells collected from the patient, a process known as autologous transplantation — yet this may explain why MSCs have not been effective. It's possible that pre-existing neurological conditions may alter stem cells' responsiveness as well as their therapeutic activity. To see whether that is in fact the case, team members collected stem cells from the bone marrow of EAE mice. But these stem cells were unable to improve EAE symptoms, whereas stem cells collected from healthy mice retained all their therapeutic potential and improved EAE symptoms. A more detailed analysis showed that the MSCs derived from EAE animals had different features than their healthy counterparts. In addition, the team confirmed that MSCs collected from MS patients were also less effective in treating EAE animals, compared to MSCs from healthy controls. Indeed, these MSCs from patients produced pro-inflammatory signals instead of the protective anti-inflammatory ones. “Diseases like EAE and MS diminish the therapeutic functionality of bone marrow MSCs, prompting re- evaluation about the ongoing use of autologous MSCs as a treatment for MS,” the team wrote, adding that its study supports the advancement of MSC therapy from donors rather than autologous MSC therapy to treat MS while raising "important concerns over the efficacy of using autologous bone marrow MSCs in clinical trials."

A new study reports that vitamin D supplements do not prevent bone loss in multiple sclerosis patients who are not vitamin-D-deficient. Previous research has suggested that low levels of vitamin D increase the risk of a person developing MS. In addition, Vitamin D prevents loss of bone density. That loss can lead to fractures and osteoporosis, a condition that many MS patients experience as their disease progresses. Researchers decided to investigate the effect of weekly doses of vitamin D3 on patients with relapsing-remitting multiple sclerosis, versus patients receiving a placebo. All 68 participants in the Phase 4 clinical trial also received 500 mg a day of calcium, a compound that is also important for bone health. The team measured the effectiveness of the supplemental vitamin D by analyzing biomarkers of bone health in blood. These included levels of the proteins PINP, or procollagen type I N propeptide, and CTX1, or C-terminal cross-linking telopeptide. At the start of the study, levels of PINP and CTX1 were not significantly different between the two groups. And that continued to be true at week 48 and week 96 of the study. The bottom line was that vitamin D supplementation did not change bone health in patients with MS after 96 weeks. “Our results do not support that high dose weekly vitamin D supplementation is beneficial for bone health in ambulatory persons with MS, and suggest that weekly vitamin D supplementation alone is not sufficient to prevent bone loss in persons with MS who are not vitamin D deficient,” the researchers concluded. The results were different from previous studies supporting the beneficial effects of vitamin D supplementation in MS patients. The researchers said they believed the discrepancy was due to differences in the studies' patient characteristics, sample size, and duration of follow-up.

Fatigue, limited mobility, and poor self-esteem or resiliency were found to be associated with periods of serious depression among multiple sclerosis patients, according to a recent study. Previous research has suggested that MS patients are at risk of major depression, with potentially profound impact on their quality of life. But only a few studies have addressed the incidence of depression among MS patients or the risk factors that may underlie its occurrence. Researchers in Canada enrolled 188 MS patients being treated an Alberta clinic, who were interviewed to assess potential risk factors for depression: namely, socioeconomic status, disease-related factors, childhood risk factors, psychosocial factors, and health behaviors. Participants were also asked to complete the Patient Health Questionnaire every two weeks for six months to identify depressive symptoms in real-time. Over a six-month follow-up, 36 cases of depression were reported among the group of MS patients analyzed. The incidence of depression was 0.019 for women, but higher — 0.044 — for men. Importantly, several factors seemed to be associated with depression in these patients — fatigue, limited mobility, and low resiliency, self-esteem, and self-efficacy, as well as poor coping skills. Results also showed that gender and income were associated with depression. Overall, the researchers concluded that "depression in MS exhibits a risk factor profile similar to that of depression in the general population, with the additional impact of MS illness-related factors. Potentially modifiable risk factors, such as coping with stress and resiliency, present opportunities for focus of further research in depression in MS treatment and prevention efforts." Concerning treatment, the team also emphasized that "while there is evidence in the clinical context that supports the efficacy for pharmacologic and non-pharmacologic treatments for depression in the general population, there is currently insufficient evidence to support/or refute the efficacy of depression treatment for individuals with MS ... Clearly this is an area that requires additional research."

Costs associated with multiple sclerosis increase as the disease worsens, according to a study of more than 16,000 patients in 16 European countries. The study, “New insights into the burden and costs of multiple sclerosis in Europe,” was published in the Multiple Sclerosis Journal. Researchers obtained their information from patient self-reporting. Patients used the Kurtzke's Expanded Disability Status Scale (EDSS) to assess the severity of their disease. They also reported on their quality of life and their resource use. Patients were divided into three categories. Those with a score between 0 and 3 on the EDSS scale were deemed to have a mild disease. The disease of those with scores of 4 to 6.5 was considered moderate. And the disease of those with scores of 7 to 9 was classified as severe. Patients assessed their health-related quality of life with the EuroQol Five Dimensions questionnaire. The average age of the 16,808 participants was 51 and a half years old. The work capacity of MS patients dropped from 82 percent of a healthy person's to 8 percent as the severity of the disease increased, researchers said. Patients' quality of life scores were about the same as those seen in the general population when they had a mild disease. But they plunged to less than zero when their disease became severe. The mean annual cost of having a mild form of MS was 22,800 euros, or around $26,300, researchers reported. The cost of having a moderate disease was 37,100 euros, or about $42,800. And the cost of a severe disease was 57,500 euros, or $66,340. Healthcare accounted for 68 percent of total costs with a mild disease, 47 percent with a moderate disease, and 26 percent for a severe disease. "Costs are dependent on the availability, use and price of services and on disease severity," the researchers wrote. "Costs were related to disease severity" in all countries "and were dominated by production losses, non-healthcare costs and DMTs," or disease-modifying therapies. Those therapies may be a key reason why the highest percentage of healthcare costs occurred in patients with a mild disease, researchers said. Doctors prescribe a lot of DMTs to this group. Other factors related to the high percentage were that many patients with mild diseases are still able to work -- meaning they incur fewer production-loss costs -- and this group requires fewer community services. As MS becomes more severe, patients' production losses rise, and they use more community services. "The intensity of healthcare service use varied widely across the countries," researchers wrote. "This reflects differences in healthcare organization, medical traditions, ease of access and – most importantly – availability of given services." Researchers also assessed patients' levels of fatigue and cognitive difficulties. Ninety-five percent reported fatigue, and 71 percent cognitive difficulties. Fatigue and cognitive difficulties had significant impacts on quality of life scores, researchers said.

A recent patient survey reveals that almost one in four people with multiple sclerosis in the U.K. are not aware of available treatments that could help delay the onset of disability, even though a clear majority put disability as a chief worry. The report, funded by Sanofi Genzyme, was conducted by Adelphi…

In a pilot study with patients with multiple sclerosis, high-intensity interval training combined with resistance training improved physical capacity and quality of life in a pilot study of multiple sclerosis (MS) patients — whether or not they were disabled. French researchers at the University of Strasbourg assessed physical capacity, strength and quality of life before the training started, and then again after completing a 12-week exercise program. They divided participants into two groups: one of 18 patients with no disabilities, and a group of eight with disabilities. Participants followed a personalized exercise program involving both high-intensity interval training — a kind of cardiovascular exercise strategy alternating short periods of intense anaerobic exercise with less intense recovery periods — and resistance training to improve muscular strength and endurance. Scientists used a French version of the Multiple Sclerosis Quality Of Life-54 test — a questionnaire filled out by MS patients to measure health-related quality of life — with five additional questions. After the exercise program, women improved significantly in vitality, general well-being and physical health composite scores in the quality of life assessment, while men showed no significant improvements. Vitality and general well-being only improved in the group with no disability. Peak oxygen consumption improved by 13.5 percent, and maximum tolerated power — a measure of maximum energy that can be expended — by 9.4 percent. Muscle strength increased in both quadriceps and hamstrings. Women showed better improvements than men in peak oxygen consumption, maximal tolerated power, strength in both quadriceps and hamstrings, and quality of life. Both groups showed increased peak oxygen consumption and strength. “Our study has shown that high-intensity interval training combined with resistance exercise training induced an improvement in physical capacity and quality of life. Moreover, this study allowed patients, irrespective of their sex or EDSS [Expanded Disability Status Scale] score, to resume exercise autonomously,” the team wrote. "High-intensity interval training is well tolerated too and can be used in clinical rehabilitation with resistance training, in both men and women with and without disabilities."

First-line treatment with Copaxone (glatiramer acetate) benefits relapsing-remitting multiple sclerosis (RRMS) patients by boosting the number of anti-inflammatory immune cells and restoring the balance of regulatory immune cells, an Italian study shows. The study, “Biological activity of glatiramer acetate on Treg and anti-inflammatory monocytes persists for more than 10…

Women who breastfeed for 15 months or longer may have a lower risk of developing multiple sclerosis (MS) than those who breastfeed for shorter periods or not at all, according to a recent study. The study also suggests that women who had their first…

People with multiple sclerosis have high levels of pro-inflammatory TH17 immune cells in their intestines that correlate with change in the micro-organism mix in their gut and the levels of their disease activity, a study reports. Researchers said the findings suggest that diet, probiotics and therapies that regulate TH17 cells could help treat MS. Probiotics are supplements containing beneficial bacteria. The study, “High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis,” was published in the journal Science. Research has shown that TH17 cells, also known as T helper 17 cells, play a role in the development of MS. In fact, they were the first harmful immune T-cells to infiltrate the central nervous system, according to studies in animals Where TH17 cells become activated has been unclear, however. Studies in mice suggested it was mainly in the small intestine. Research has also indicated that their activation increases the potential for a person to develop an autoimmune brain disease like multiple sclerosis. An autoimmune disease occurs when the immune system, which defends the body against disease, decides that a person's healthy cells are foreign, and attacks those cells. Researchers decided to see if the findings in mouse models of MS applied to people with the disease. They discovered a link between higher levels of TH17 cells in MS patients' intestines and autoimmune brain problems. They also found a correlation between higher levels of TH17 cells and changes in patients' gut microbiome. The team then identified which bacteria were changing in the gut. Patients with increased levels of TH17 cells and higher disease activity had a higher ratio of Firmicutes to Bacteroidetes bacteria and more Streptococcus strains in their gut, particularly Streptococcus mitis and Streptococcus oralis. Previous studies have shown that these species promote TH17 cell differentiation in humans. Cell differentiation involves a cell transforming from one cell type to another — usually a more specialized type. This dramatically changes a cell's size, shape, metabolic — or fuel-burning — activity, and responsiveness to signals. Some studies have suggested a link between T-cell differentiation and brain autoimmune diseases. “On the basis of our findings, we speculate that, under certain conditions, or because of still unknown virulence factors, these Streptococcus strains can colonize the small intestine and favor TH17 cell differentiation in the human gut mucosa [linings],” researchers wrote. In addition to more Streptococcus bacteria, the team detected lower levels of Prevotella bacteria in MS patients with disease activity than in healthy controls or patients with no disease activity. This decrease may also promote TH17 cell differentiation because “Prevotella is capable of producing the anti-inflammatory metabolite propionate that limits intestinal TH17 cell expansion in mice," the researchers wrote. Overall, the team concluded that “our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive TH17 cell expansion in the human intestine.” The findings suggest that regulating TH17 cell expansion, along with changes in diet aimed at regulating intestinal linings, could be ways to help treat MS.

Patient questionnaires can be sensitive to signs of disease progression and worsening in neurological disorders like multiple sclerosis just as they are in other diseases, helping doctors to better predict clinical outcomes in patients, a study reports. Particularly, the study found that MS patients with higher scores on a specific disease questionnaire were nearly six times more likely to die within 10 years than those with lower scores, and that mortality risk also jumped among people whose scores rose on a second taking of same questionnaire. But the researchers cautioned that their study was not a tool for predicting mortality but a way to help patients be more active participants in their care. “Our research shows that by answering a set series of questions, patients can have an important role in predicting long-term prognosis in diseases like MS, and that these types of questionnaire should be used by doctors to get a better idea of the patient’s health,” Joel Raffel, study’s first author, from the Imperial College London, United Kingdom, said in a university news release written by Ryan O'Hare. “We hope that using patient-reported outcomes like these more and more will mean a shift towards empowering patients," he added. "They will be able to provide their own data, so rather than the doctor telling the patient how they are doing, it’s the other way around.” Among tools often used in the clinic are patient-reported outcomes; that is, questionnaires for patients that focus on their disease and treatment. But while these questionnaires have many uses, from screening for symptoms or evaluating treatment response to improving communications, they are often under-utilized when people have MS or other neurological diseases, "in part because it is not clear if PROs [patient-reported outcomes] relate to ‘hard clinical outcomes’ like disability or mortality," the team noted. Researchers wanted to determine whether the Multiple Sclerosis Impact Scale–29 (MSIS-29) — a 29-question survey assessing quality of life and disease impact over the previous two weeks — might serve as a way of predicting a patient's risk of death. The questionnaire was completed by 2,126 people, registered with the MS Society Tissue Bank in the U.K., beginning in 2004. Of these, 872 patients repeated it one year later. By 2014, the researchers reported that 264 of the original group of MS patients (12.4%) had died, and an evaluation revealed that MSIS-29 scores were associated with 10-year mortality risk regardless of age, gender, and disability score at the time the questionnaire was completed. Indeed, patients with high scores on the MSIS-29 questionnaire, indicative of a poor quality of life, were 5.7 times more likely to die within 10 years than those whose scores were lower. The mortality risk rose further among people whose MSIS-29 score worsened between the first and second year of answering the questionnaire. “Ideally, these questionnaires should be administered routinely, once a year in the clinic or online,” Raffel said. “This could help doctors to understand what issues the patients are facing and could also help to answer big research questions around prognosis and which of the available treatments we have for MS are working.” The team believes that questionnaire responses, together with usual clinical assessment tools like imaging data through MRI scans, could help doctors and patients choose the best course of treatment.

A herpes virus that lies dormant in many people can hinder the repair of the neuron-protecting myelin sheath whose deterioration causes multiple sclerosis, a study reports. The finding about the HHV-6 virus may help explain differences in the symptoms and progression of the disease from person to person, researchers said.

According to a new clinical trial, the allergy treatment cetirizine fails to alleviate a flu-like condition that interferon-beta treatment generates in people with relapsing-remitting multiple sclerosis. The results, which surprised researchers, apply to flu-like syndrome, or FLS. Cetirizine is an over-the-counter medicine sold under the brand names Zirtec, Zyrtec, Reactine, and Triz. FLS affects roughly 75 percent of patients who take interferon-beta, also known as IFN-beta. It can cause fever, chills, muscle pain, weakness, and headache. The symptoms commonly occur three to six hours after an IFN-beta injection and last up to 24 hours. Although FLS usually subsides in the first three months of IFN-beta therapy, it persists in some patients, causing them to miss doses or even discontinue the treatment. Cetirizine is an antihistamine for hay fever and allergies. The purpose of the clinical trial was to determine whether cetirizine could alleviate RRMS patients' FLS. In order to determine study results, patients did self-assessments of how much discomfort their FLS caused them. There were no significant changes in the two groups' average self-assessment scores at four and eights weeks of treatment, suggesting that cetirizine does not offer significant benefits to RRMS patients with FLS. “The addition of a [cetirizine] to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to improve symptoms significantly compared with placebo," the team wrote. "FLS continues to be inadequately treated in many RRMS patients. Further investigations are needed to elucidate the underlying mechanisms of IFNβ-induced FLS and develop adequate strategies for prevention and treatment."

A new study on rats indicates that the antidepressant Luvox promotes the production of the neuron-protecting coating that is deficient in multiple sclerosis. It also significantly decreased the severity of the animals' disease, researchers said, adding that Luvox promoted the production of the protective coating by helping stem cells evolve into oligodendrocytes, or cells that generate what is known as the myelin sheath. Patients with MS often experience anxiety and depression, with recent studies suggesting their rate of depression is three times higher than those with other long-term medical conditions. In addition to drugs targeting the underlying mechanisms of MS, such as inflammation and myelin loss, doctors often recommend that patients take antidepressants. The most common treatments they prescribe for moderate or severe depression are a class of serotonin re-uptake inhibitors that include Luvox. Few studies have looked at antidepressants' effects on animal models of MS, however. That prompted researchers to investigate Luvox's impact on both laboratory and rat models of the disease. Researchers used embryonic neural stem cells in their study. Luvox prompted laboratory stem cells to evolve into other types of cells, including neurons, oligodendrocytes, and astrocytes, which have several roles, including supporting and repairing neurons. Prozac also promoted stem cell differentiation — but at levels 10 times higher than those of Luvox. A key finding was that that Luvox significantly decreased the severity of the disease in the rats. Another important finding was that Luvox significantly reduced demyelination and immune cell infiltration in the rats' spinal cords. It also decreased the rats' expression of pro-inflammatory proteins known as cytokines. Overall, this study “demonstrated that fluvoxamine, in addition to its confirmed role in mood disorder therapy, could serve as a candidate clinical treatment for attenuating [reducing] neuro-inflammation and stimulating oligodendrogenesis in neurological diseases, particularly MS patients.”

A recent study has found that continued use of Ampyra (dalfampridine extended-release, sold in the U.S. by Acorda Therapeutics) by patients with multiple sclerosis (MS) lowers both inpatient hospital visits and overall healthcare costs. Results from the study, titled “Inpatient Admissions and Costs Associated with Persistent…

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.

How cool is this? Though it's not yet related to multiple sclerosis, researchers are developing a Band-Aid-size patch that can inoculate someone with the flu vaccine. The patch is made up of 100 solid, water-soluble microneedles that are just long enough to penetrate the skin. They’re contained in an area about the size of a dime. Adhesive helps the patch grip the skin during the administration of the vaccine, which is encapsulated in the needles and is released in about 20 minutes, as the needle tips dissolve. The patch is then peeled away and discarded like a used bandage strip. The researchers, working at Georgia Tech and Emory University, report that in their Phase I clinical trial the patch was just as effective in generating immunity against the flu as the traditional flu shot. They believe the microneedle patch can save money because it is easily self-administered, it can be transported and stored without refrigeration, and it’s easy to dispose of without needing a sharps waste container. Above all, says principal investigator Nadine Rouphael, MD, of the Emory University School of Medicine, “having the option of a flu vaccine that can be easily and painlessly self-administered could increase coverage and protection by this important vaccine.” Now, I don’t want to jump the gun. Although the researchers are working to develop these microneedle patches for use with other vaccines, including measles, rubella and polio, they’ve only completed the first phase of their clinical trials. They’re now planning a Phase 2 trial with more participants. Whether MS drugs might, someday, be administered this way is anyone’s guess. But, it certainly would be nice if one day, instead of jabbing yourself in the thigh for your scheduled MS shot, you could deliver your MS medication by just putting a Band-Aid on your skin.

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…

A gene mutation may explain the uncontrolled, inflammatory immune response seen in autoimmune and chronic inflammatory diseases like multiple sclerosis, scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) report. It's a discovery that, they said, appears to be "a big step in the right direction." According to the study, published in the journal Science Immunology, alterations in the FOXP3 gene affect specific immune cells called regulatory T-cells, or Tregs. Those mutations hamper Tregs in performing a crucial regulatory role, leading to a loss of control over the immune system’s response to a perceived threat. “We discovered that this mutation in the FOXP3 gene affects the Treg cell’s ability to dampen the immune response, which results in the immune system overreacting and causing inflammation,” Ciriaco Piccirillo, the study's lead author and an immunologist in the Infectious Diseases and Immunity, Global Health Program, at the RI-MUHC, said in a news release. Tregs are known to be the immune system players responsible for keeping other immune cells under control, preventing them from attacking the host’s own tissues, while maintaining a proper immune response against harmful agents. The normal activity of Treg cells is essential for preventing excessive immune reactions. The FOXP3 gene is also well-known, and documented, to be essential for proper Treg cell function. However, the mechanisms by which FOXP3 gene is involved in Treg cell activities are still poorly understood. In the study, “Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions,” the research team — in collaboration with researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan — evaluated the impact of a FOXP3 gene mutation in autoimmunity response. Taking advantage of cutting-edge technology, the team studied samples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. Interestingly, the researchers found that this genetic variant did not reduce the number of Treg cells or the levels of FOXP3 protein. Instead, the mutation altered the way Tregs could suppress other immune cells to prevent overactivation. “What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response,” said Piccirillo. “Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions,” added Khalid Bin Dhuban, the study's first author and a postdoctoral fellow in Piccirillo’s laboratory. The team developed a compound capable of restoring Treg cells' ability to control the immune system in the presence of this specific FOXP3 gene mutation. Tested in animal models of colitis and arthritis, two chronic inflammatory diseases, the compound reduced inflammation and restored normal Treg function. Researchers now plan to develop similar drugs that may be of use in other diseases where Treg cells are known to be defective, including multiple sclerosis, type 1 diabetes, and lupus. "Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," said Piccirillo. “Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer.” “This discovery gives us key insights on how Treg cells are born and how they can be regulated,” Piccirillo added. “With this discovery, we are taking a big step in the right direction.”

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…

MSBase and icometrix have joined efforts in a large-scale project to identify imaging markers of multiple sclerosis (MS) that could help diagnose the disease in its early stages. The combination of magnetic resonance imaging (MRI) information collected from MS patients with clinical information from the MSBase Registry can offer new insights in disease progression, potentially leading to new predictive tools for MS. It may also promote more standardized use of imaging measures in clinical practice. With more than 52,000 MS patients, the MSBase Registry is an international database committed to collecting patients’ information as well as sharing, tracking and evaluating overall outcome data in MS and other neurological conditions. Until now, the MSBase Registry included only descriptive information regarding patients' imaging analysis results, with no access to full imaging data. This joint, large-scale project will include MRI scan data routinely acquired in clinical setting taking advantage of icometrix’s software platform, MSmetrix. “We wish to unlock the power of MRI for personalized monitoring in MS," Helmut Butzkueven, director of MSBase, said in a press release. "The MSBase Scientific Leadership group has selected MRI integration as the top strategic priority for MSBase. We believe that already conducted MRI scans represent an enormous missed opportunity, because advanced measurements to assess change over time from these scans are not currently in practical use.” Butzkueven said MSBase "will test the predictive power of this unlocking of MRI data in the first phase," with a total of 10,000 MRI data points in at least 3,000 MS patients from all over the world. The project is expected to identify disease progression markers that could help detect early signs of MS by MRI evaluation. This investigator-initiated collaboration between icometrix and the MSBase Foundation is being supported by three global pharmaceutical giants: Novartis, Biogen and Roche. “MRI measures play an essential part in the complex puzzle of MS,” said Danny Bar Zohar, global head of neuroscience development at Novartis. “Partnering with MS Base and icometrix in this exciting project will bring the acquisition of high-quality real world data to the next level, ultimately improving the outcome of people living with MS.”

Problems with sense of smell are more frequent and severe in patients with primary progressive multiple sclerosis (PPMS) than in those with relapsing-remitting multiple sclerosis (RRMS), a study reports. The research, “Olfactory dysfunction in patients with primary progressive MS,” was published in the journal Neurology: Neuroimmunology and Neuroinflammation. A distinguishing feature of RRMS, the most common form of the disease, is attacks of new or increasing neurologic symptoms, such as movement disorders, and then recovery periods. About 15 percent of patients have the primary progressive form, or PPMS. Its main feature is gradually increasing neurologic disability without recovery periods. Some scientists believe PPMS is a less inflammatory course of MS. The differences in the processes that underlie each form are not well understood, however. Several researchers think that studying differences in the two groups' ability to smell — or olfactory dysfunction — could shed light on these underlying processes. Autopsies of MS patients in one study showed that 71 percent had experienced demyelination, or loss of neurons, in the brain's olfactory pathway. The processes that led to this dysfunction were unclear, however. Researchers decided to test the hypothesis that olfactory impairment is more pronounced in patients with PPMS than RRMS. The team examined 32 patients with PPMS, 32 with RRMS, and 32 healthy controls. The yardstick they used to evaluate sense of smell was the olfactory Threshold Discrimination Identification (TDI) Test. It involves patients smelling 48 sniffin' sticks. In addition to an overall TDI, there were subscores on olfactory threshold, odor identification and odor discrimination. Olfactory threshold refers to the lowest concentration of an odor that a person can detect. Researchers found olfactory dysfunction in 27, or 84 percent, of the PPMS patients; 10, or 31 percent, of the RRMS patients; and 1, or 3 percent, of the healthy controls. The TDI score and all subscores were significantly worse in patients with PPMS than in the controls, when considering patients of similar age and the same sex. The TDI score was also worse in PPMS patients than in the RRMS group, after adjusting for age, sex, MS disability level, the length of time patients had the disease, and patients' ability to identify and discriminate among odors. Researchers acknowledged limitations to the study. One was the small size of the groups in the research. Another was not using magnetic resonance imaging, or MRI, to measure olfactory pathway deterioration. Comparing the brain's olfactory pathway region with other brain regions in both the RRMS and PPMS groups could have shed light on the processes underlying the olfactory dysfunction differences between the two, researchers said. “The findings suggest that olfactory dysfunction might be a surrogate of neurodegeneration in these patients," the researchers wrote. "Studies correlating olfactory function with radiologic and clinical markers of disease progression would be of interest.”

A variation in the NLRP1 gene is associated with multiple sclerosis that runs in families, Slovenian researchers report. Their study, “Identification of rare genetic variation of NLRP1 gene in familial multiple sclerosis,” was published in the journal Scientific Reports. The research was led by Dr. Borut Peterlin of Ljubljana University Medical Center's Clinical Institute of Medical Genetics. Scientists believe MS arises from a combination of a person's genetic background and the environment. Although previous studies have suggested that genes are behind MS that runs in families, researchers had yet to confirm that hypothesis. The Slovenian team wanted to identify any genes that were at play in both the MS and malignant melanoma that two siblings had. Although disease surveys indicate the two conditions can occur together, scientists had been unable to identify a shared cause for the two conditions. Interestingly, research has shown a link between a person's susceptibility to MM and a mutation of the NLRP1 gene. And recent studies have indicated that NLRP1 plays a role in the development of MM. The Slovenian team decided to evaluate the association between an NLRP1 mutation and multiple sclerosis in two groups. One consisted of 38 people with MS whose disease ran in the family. The other was 44 people with MS whose disease did not run in their family. Researchers used genomic, molecular biology and immunology measurements to decide whether there was a link between the mutation and MS. They found a connection between the mutation and MS that runs in families. The mutation affects the function of the protein the gene generates — a protein known to be involved in inflammatory processes. Researchers also found other NLRP1 mutations in patients with and without a family history of MS that they believe could be involved in the development of the disease. In addition, the team found evidence of a connection between MS associated with NLRP1 mutations and the development of MM. That evidence involved immune responses to the two conditions. Stimulating the production of immune-system components known as peripheral blood mononuclear cells, or PBMCs, triggered immune responses in MS patients with NLRP1 mutations. The responses included increased production of the pro-inflammatory cytokine IL-1β. Higher levels of that protein have been found in MM tissue. PBMCs include such immune cells as lymphocytes, monocytes, and macrophages. "IL-1β has been implicated in a variety of inflammatory and neurodegenerative processes occurring in MS,” the researchers wrote. Overall, the findings demonstrated an association between MS running in families and MM, they said. And the genetic link between the two may be the NLRP1 gene mutation, they added. The team said scientists might be able to develop a treatment for MS by finding a way to lower the increased production of IL-1β that NLRP1 mutations trigger.

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…

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…