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Patricia Inacio, PhD

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Patricia holds her PhD in cell biology from the University Nova de Lisboa, Portugal, and has served as an author on several research projects and fellowships, as well as major grant applications for European agencies. She also served as a PhD student research assistant in the Department of Microbiology & Immunology, Columbia University, New York, for which she was awarded a Luso-American Development Foundation (FLAD) fellowship.

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Articles by Patricia Inacio, PhD

News

Increase in Blood-Brain Barrier Protein May Protect Against MS, Study Finds

One way the body may protect itself from nerve cell inflammation is to have cells in the blood-brain barrier increase their production of a protein that keeps immune cells from entering the brain, researchers in Germany and Canada report. The finding suggests that scientists could develop a multiple sclerosis therapy around the protein, known as EGFL7. It would work by preventing as many inflammation-generating immune cells from entering the brain. The underlying trigger for MS is immune cells crossing the blood-brain barrier to invade the central nervous system (CNS). The barrier is a selective membrane that shields the CNS from general blood circulation. Therapies that prevent immune cells from entering the brain can help control the disease, studies have shown. They include Tysabri (natalizumab, marketed by Biogen). But “as with other highly effective disease-modifying therapies which influence a broad range of peripheral immune cells, potential devastating adverse events limit the use of this therapy as a first-line agent,” the researchers wrote. The team at Mainz University Medical Center in Germany and the University of Montreal wondered if epidermal growth factor-like protein 7 (EGFL7) could prevent the brain inflammation in MS.  Although scientists had not previously linked it to MS, it was shown to regulate the migration of immune cells into breast cancer tumors. The CNS response to the chronic inflammation seen in MS patients and a mouse model of the disease was to increase EGFL7 in the blood-brain barrier, the researchers found. Researchers said the increase prevented pro-inflammatory immune cells from crossing into the CNS. Endothelial cells that line blood capillaries in the blood-brain barrier are the ones that secrete EGFL7. “We postulate that EGFL7 upregulation by BBB-ECs [brain blood barrier-endothelial cells] is induced as a compensatory mechanism to promote survival and recovery of BBB function in neuroinflammatory conditions,” the team wrote. Researchers then tested what happened in mice that lacked EGFL7. They found that the mice developed MS earlier and that their blood-brain barrier membrane was less efficient at keeping immune cells out. Treatment with EGFL7 improved the disease severity in the MS mice and tightened the blood-brain barrier, they said. “In light of our findings, smaller EGFL7 agonists, in development for other diseases, could therefore constitute an appealing therapeutic avenue for MS,” the team concluded.

News

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 they’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 cells 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 Cambridge 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, called 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. “Our mouse study suggests that using a patient’s reprogrammed cells could provide a route to personalized treatment of chronic inflammatory diseases, including progressive forms of MS,” Stefano Pluchino, a principal researcher in Cambridge's Department of Clinical Neurosciences, said in a press release. “This 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,” said Pluchino, the study's lead author. Luca Peruzzotti-Jametti, a Wellcome Trust research training fellow, said the discovery would not have been possible without a multidisciplinary collaboration. “We made this discovery by bringing together researchers from diverse fields, including regenerative medicine, cancer, mitochondrial biology, inflammation and stroke, and cellular reprogramming."

News

#ACTRIMS2018 – Oryzon Enrolls First Patient in SATEEN Trial, Presents New Data at MS Meet

Oryzon Genomics has enrolled the first multiple sclerosis patient in its Phase 2a SATEEN clinical trial investigating the therapy ORY-2001. The Spanish company will also present new results from preclinical models of MS treated with ORY-2001 at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2018, set for Feb. 1-3 in San Diego. ORY-2001 is an epigenetic therapy, meaning it targets the expression and activity of genes. The drug inhibits two particular molecules, LSD1 and MAOB, and was previously shown to reduce cognitive impairment and neuroinflammation in preclinical models, including in a mouse model of MS — the experimental autoimmune encephalomyelitis (EAE) model. The therapy was also shown to have neuroprotective effects. During ACTRESS 2018, Oryzon's chief scientific officer, Tamara Maes, will present a poster, "ORY-2001 reduces inflammatory cell infiltration in the Theiler’s murine encephalomyelitis virus model and highlights the epigenetic axis in MS.” “In previous reports we showed that ORY-2001 reduces the clinical score, lymphocyte egress, immune cell infiltration and inflammation protecting the spinal cord from demyelination in a murine MS-EAE model,” Maes said in a press release. “Here we provide data on the efficacy of ORY-2001 in the Theiler’s murine encephalomyelitis virus model for multiple sclerosis." In a second poster, "ORY-2001 in multiple sclerosis: first clinical trial of a dual LSD-1/MAOB inhibitor,” Roger Bullock, Oryzon's chief medical officer, will detail the Phase 2a trial, SATEEN, testing ORY-2001 in patients with relapsing-remitting or secondary progressive MS over a 36-week period, followed by an open-label extension. “Our first patient enrolled in SATEEN signals a new landmark for the clinical development of this drug in different neurological indications,” said Bullock. “This is the first epigenetic approach in this disease, and we hope that it will contribute to enlarge and improve the therapeutic options for patients afflicted by MS."

News

MS Patients’ High Osteopontin Protein Levels Make It a Potential Biomarker for the Disorder, Study Reports

Multiple sclerosis patients have high levels of a protein called osteopontin in their cerebrospinal fluid and blood, making it a potential tool for diagnosing the disease and predicting its course, a study suggests. The research, “Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis,” was published in the journal PLOS One. Researchers wanted to know if levels of osteopontin in cerebrospinal fluid and blood could be a reliable biomarker for MS. To arrive at answer, they “conducted a systematic review and meta-analysis" of studies that had measured the protein's levels in cerebrospinal fluid and blood "in MS patients and controls." The team searched for studies in three databases — PubMed, Web of Science and Scopus. Out of 27 that met their criteria, they used 22 in the meta-analysis. All four types of MS were represented in the studies — clinically isolated syndrome, relapsing-remitting MS, secondary progressive MS, and primary progressive MS. There were three types of controls in the articles — healthy people, people with non-inflammatory neurological disorders, and people with inflammatory neurological disorders. Researchers' first observation was that all of the MS patients had higher levels of osteopontin than controls. The protein's levels were significantly higher in relapsing-remitting MS patients than in those with clinically isolated syndrome, the group with the lowest osteopontin levels. Levels were similar in the other types of MS. Patients with an active disease had significantly higher levels of the protein in their cerebrospinal fluid than those with a stable disease. The results supported previous studies' findings that osteopontin levels are higher than normal in the cerebrospinal fluid and blood of MS patients, strengthening the notion that it could be used as a biomarker for MS. “Given the fact that OPN [osteopontin] levels are higher during relapses, we think that by monitoring this biomarker,  we might be able to predict the disease course," the team wrote. "We propose that developing drugs modulating OPN concentration may be a new treatment strategy for MS."