stem cells

Top 10 Multiple Sclerosis Stories of 2018

Multiple Sclerosis News Today brought you daily coverage of key findings, treatment developments, andĀ clinical trials related to multiple sclerosis (MS) throughout 2018. We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2019. Here are the top 10 most-read articles of…

Stem Cell Transplant Lessens Disability and Relapses in RRMS Patients, Phase 2 Trial Shows

Treatment withĀ autologous hematopoietic stem cell transplantĀ (aHSCT) led to a sustained decrease in disability and almost no clinical relapses in patients withĀ relapsing-remitting multiple sclerosisĀ (RRMS)Ā who had failed to respond to prior immunosuppressive therapies, an Australian Phase 2 trial shows. Trial findings were published in the study, ā€œProspective phase…

Stem Cells from MS, Parkinson’s Patients Voyaging to Space Station to Study Disease Impact on Brain in Microgravity

Stem cellsĀ from patients with Parkinsonā€™s diseaseĀ and primary progressive multiple sclerosis (PPMS) are soon to voyage into space, and be brought aboard the International Space Station so cell-to-cell interactions in these neurodegenerative diseases can be studied withoutĀ gravitational forces acting on them. This research project, proposed to launch in May…

#ECTRIMS2018 – Finding Best Treatment for ‘Right Patient’ and Progressive MS Among Work of Interest, Cleveland Clinic Doctors Say

Tailored, highly effective therapies early in the disease’s course may be a way forward in multiple sclerosis (MS)Ā treatment, according to Cleveland Clinic neurologist Robert Bermel. Another neurologist with the Cleveland Clinic,Ā Robert Fox, talked about potential and upcoming progressive MS treatments.Ā  In interviews with Multiple Sclerosis News…

Circumvention Tourism, Revisited

In a previous column, I wrote about circumvention tourism, in which patients travel to another country to access a medical treatment that is unavailable in their home country. I wrote it in response to someone in the MS community who promoted travel to an offshore island…

Researchers Succeed at Generating Oligodendrocytes, Key to Myelin Renewal, in Tissue Created in Lab

Researchers atĀ Case Western Reserve University School of MedicineĀ have developed a cutting-edge laboratory technique able to turn human stem cellsĀ ā€“ special cells able to grow into any type of cell in the body ā€“ into brain-like tissues in a culture dish. They intend to use their tool to study how myelination ā€“ the deposition of myelin around nerve cells ā€“ occurs in the central nervous system, and how diseases such as multiple sclerosis (MS) impair this process. The experimental protocol to grow these structures outside an organis) is described in the study, "Induction of myelinating oligodendrocytes in human cortical spheroids," published in the journalĀ Nature Methods. These structures, called ā€œoligocortical spheroids,ā€ are small spheres that contain all the major cell types usually found in the human brain, including oligodendrocytes ā€” cells that produce myelin, which is the fatty substance that insulates nerve fibers. Previous cerebral organoid techniques failed to include oligodendrocytes. ā€œWe have taken the organoid system and added the third major cell type in the central nervous system ā€” oligodendrocytes ā€” and now have a more accurate representation of cellular interactions that occur during human brain development,ā€ Paul Tesar, PhD, associate professor of genetics and genome sciences at Case Western's medical school and the study's senior author, said in a press release. Oligodendrocytes are essential to good brain health. Without these cells, myelin production is hampered and nerve cells cannot communicate effectively, and eventually they start to deteriorate. This is the starting point for many neurological disorders caused by myelin defects, including MS and rare pediatric genetic disorders like Gaucher disease. Using this new organoid system and these myelin-producing cells, researchers intend to study the process of myelination ā€” how it occurs in normal circumstances and how neurodegenerative diseases disrupt this process. ā€œThis is a powerful platform to understand human development and neurological disease,ā€ Tesar said. ā€œUsing stem cell technology we can generate nearly unlimited quantities of human brain-like tissue in the lab. Our method creates a ā€˜mini-cortex,ā€™ containing neurons, astrocytes, and now oligodendrocytes producing myelin. This is a major step toward unlocking stages of human brain development that previously were inaccessible.ā€ Researchers not only demonstrated that they were capable of generating mature oligodendrocytes derived from human stem cells in vitro, but they also showed these cells were able to exert their function and produce myelin starting at week 20 in a culture dish. Their improved organoid system could also be used to test the effectiveness of potential myelin-enhancing treatments. ā€œThese organoids provide a way to predict the safety and efficacy of new myelin therapeutics on human brain-like tissue in the laboratory prior to clinical testing in humans,ā€ said Mayur Madhavan, PhD, co-first author on the study. To prove this point, researchers treated organoids with promyelinating compounds known to enhance myelin production in mice, and measured the rate and extent ofĀ oligodendrocyte generation and myelination. Under normal conditions, adding promyelinating drugs to cultured organoids increased the rate and extentĀ of oligodendrocyte generation and myelin production, the team reported. But results differed in important ways using diseased organoids. Ā Specifically, treating organoids generated from patients with Pelizaeus-Merzbacher disease ā€” a fatal genetic myelin disorderĀ ā€” brought an in vitroĀ recapitulation of the patients' symptoms. ā€œPelizaeus-Merzbacher disease has been a complicated disorder to study due to the many different mutations that can cause it and the inaccessibility of patient brain tissue,ā€ said Zachary Nevin, PhD, co-first author on the study. ā€œBut these new organoids allow us to directly study brain-like tissue from many patients simultaneously and test potential therapies.ā€ Altogether, these findings demonstrate that oligocortical spheroids could be a versatile in vitro system to study how myelination occurs in the central nervous system, and a possible model for testing new therapies for neurodegenerative disorders. ā€œOur method enables generation of human brain tissue in the laboratory from any patient,ā€ Tesar said. ā€œMore broadly, it can accurately recapitulate how the human nervous system is built and identify what goes wrong in certain neurological conditions.ā€

Blood Stem Cell Transplants Improve RRMS Patients’ Disability, Phase 3 Trial Shows

Blood stem cell transplants lead to significant improvements inĀ relapsing-remitting multiple sclerosis patients’ disability, a Phase 3 clinical trial shows. The 110 patients who took part in the MIST study (NCT00273364) were having relapses after receiving standard therapies such asĀ beta interferon, Copaxone (glatiramer acetate), Novantrone (mitoxantrone), Tysabri (natalizumab), Gilenya (fingolimod),…

Transforming Skin Cells Into Nerve Stem Cells Could Be a Way to Treat MS, Study Suggests

Reprogramming skin cells into brain stem cells, then transplanting them into the central nervous system may reduce inflammation and reverse the nerve cell damage in progressive multiple sclerosis, a mouse study shows. Scientists have dubbed macrophages the immune system's big eaters because they engulf abnormal cells like cancer in addition to invaders like viruses and bacteria. Special classes of macrophages live in a number of organs, including the brain and spinal cord, where theyā€™re called microglia. Although they protect the body, microglia can participate in the development of progressive forms of MS by attacking the central nervous system, causing nerve cell damage. MS is an autoimmune disease, or one in which the immune system can attack healthy tissue besides invaders. Recent studies have suggested that neural stem cells, which have the capacity to differentiate into any type of nerve cell, can regulate immune response and inflammation in the central nervous system. At one point, researchers obtained neural stem cells from embryos. But this technique generated only a fraction of the cells needed for treatments. Meanwhile, doctors have tried to avoid collecting stem cellsĀ from someone with a different genetic profile than the patient because this increases the risk that the immune system will attack them once they're transplanted. University of CambridgeĀ scientists decided to try reprogramming skin cells into neural stem cells. The idea behind the mouse study was that using skin cells from the same person who will receive the stem cells will reduce the chance that the immune system will attack the stem cells. In the mouse study, the team discovered a link between higher than normal levels of a small metabolite, calledĀ succinate, and chronic MS. The metabolite prompts macrophages and microglia to generate inflammation in the cerebrospinal fluid that bathes the brain and spinal cord. Transplanting neural stem cells and progenitors of these stem cells into the cerebrospinal fluid of mice improved the animals' chronic nerve cell inflammation. The stem cells reduced the animals' succinate levels and switched their macrophages and microglia from a pro- to an anti-inflammatory state. This led to a decrease in inflammation and less damage to the central nervous system. ā€œOur mouse study suggests that using a patientā€™s reprogrammed cells could provide a route to personalized treatment of chronic inflammatory diseases, including progressive forms of MS,ā€ Stefano Pluchino, a principal researcher in Cambridge's Department of Clinical Neurosciences, said in a press release. ā€œThis is particularly promising as these cells should be more readily obtainable than conventional neural stem cells and would not carry the risk of an adverse immune response,ā€ said Pluchino, the study's lead author. Luca Peruzzotti-Jametti, aĀ Wellcome TrustĀ research training fellow, said the discovery would not have been possible without aĀ multidisciplinary collaboration.Ā ā€œWe made this discovery by bringing together researchers from diverse fields, including regenerative medicine, cancer, mitochondrial biology, inflammation and stroke, and cellular reprogramming."

Cell-Based Therapies in MS Remain Experimental, Expert Group Argues in Review Article

A group of experts recently concluded that clinical trials are the best way to explore whether cell-based therapies are viable options for treating multiple sclerosis. In a newly published article, MS researchers reviewed evidence on a range of cell therapies, including stem cell transplants and delivery or stimulation of various cell types. Clinical trials, the panel argued, would be the optimal way to examine which types of cells should be used, how they should be delivered, and the types and disease stages the treatments are suitable for. The article focused on four types of cell-based treatments: autologous stem cell transplants, mesenchymal and related stem cell transplants, use of drugs to manipulate stem cells in the body to boost their ability to repair, and transplants of oligodendrocyte progenitor cells to trigger new myelin production. Loss of the myelin that protects neurons is a hallmark of MS. Such treatments hold promise to attain what current disease-modifying therapies in MS have not: halting the disease without lifelong treatment that has potential side effects, and regenerating damaged tissue. In addition to reviewing the evidence surrounding cell-based treatments, the expert group focused on the availability of the treatment options outside of controlled trials. ā€œMedia attention has resulted in some cases of misrepresentation and exaggeration of therapeutic claims for cell-based therapies for multiple sclerosis and other diseases,ā€ the team wrote. This has caused patients to seek the treatments ā€” paying out-of-pocket ā€” at unregulated clinics. The panel noted that several drugs in development, including opicinumab, are aimed at promoting remyelination. In addition, drugs that are already approved for other conditions might have remyelinating properties, and might be repurposed to treat MS. Although studies are ongoing, the panel noted that it is unclear if the drugs do promote remyelination. Despite ongoing research and ā€” in some cases ā€” clinical use of cell-based therapies for MS, these treatments should be considered experimental, the expert group concluded. They again underscored the importance of clinical trials in providing a controlled environment for patients wishing to have cell therapy, as well as a source of evidence for the feasibility of these approaches.

Pre-Existing Inflammatory Diseases Reduce Therapeutic Potential of Stem Cells for MS Treatment, Study Shows

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 ā€” 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. ā€œDiseases 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,ā€ 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."