Inflammatory Cortical Demyelination in Early Multiple Sclerosis


Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease.


We evaluated the prevalence and character of demyelinating cortical lesions in patients with multiple sclerosis. Cortical tissues were obtained in passing during biopsy sampling of white-matter lesions. In most cases, biopsy was done with the use of stereotactic procedures to diagnose suspected tumors. Patients with sufficient cortex (138 of 563 patients screened) were evaluated for cortical demyelination. Using immunohistochemistry, we characterized cortical lesions with respect to demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and a topographic association between cortical demyelination and meningeal inflammation. Diagnoses were ascertained in a subgroup of 77 patients (56%) at the last follow-up visit (at a median of 3.5 years).


Cortical demyelination was present in 53 patients (38%) (104 lesions and 222 tissue blocks) and was absent in 85 patients (121 tissue blocks). Twenty-five patients with cortical demyelination had definite multiple sclerosis (81% of 31 patients who underwent long-term follow-up), as did 33 patients without cortical demyelination (72% of 46 patients who underwent long-term follow-up). In representative tissues, 58 of 71 lesions (82%) showed CD3+ T-cell infiltrates, and 32 of 78 lesions (41%) showed macrophage-associated demyelination. Meningeal inflammation was topographically associated with cortical demyelination in patients who had sufficient meningeal tissue for study.


In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation. (Funded by the National Multiple Sclerosis Society and the National Institutes of Health.)
N Engl J Med 2011; 365:2188-2197 December 8, 2011

Immunologist Awarded Nobel Prize

Ralph Steinman's discovery and continuing investigation of a "missing link" in the human immune system have changed the field, colleagues say. This year, his work also has earned him the Nobel Prize. 
"He discovered this important cell type, dendritic cells," says Max Cooper at the University of Alabama at Birmingham, a fellow immunologist who has known Steinman and his work for more than 30 years. "Back at a time when no one really believed him, he pushed the idea very hard and backed it up by isolating this very small fraction of cells to show that they were important in activating our T‑ and B‑cells in immune responses. "His digging them out, isolating them, characterizing them in a painstaking way really did change the way we view how microbes enter the body and get recognized and responded to. And that changed our view of the way we understand how immunity is kicked off." Steinman, the director of the Chris Browne Center for Immunology and Immune Diseases at The Rockefeller University, is practiced at describing the cells he studies. "The dendritic cell is, so to speak, a missing link in the immune system," he says. "The immune system has a number of different cells that provide resistance to infection and are involved in other disease conditions like cancer, allergy, transplantation and autoimmunity. Immune cells are like musicians in a symphony, each very talented and specialized, but they need a conductor and composer, and that's what dendritic cells are." "The cells sit up at surfaces of our body, along airways and along our intestine and in our skin, ready to pick up infections that enter the body. If they find one, they pick it up to display to the immune system. The cells migrate in the body, and when they get to the immune organs—lymphoid tissues—they find the musicians, so to speak, and then orchestrate the immune response. They tell the immune cells to grow and to develop into functioning protective cells." In the 1970s, when Steinman started his research career, researchers knew about the "musician" cells and they knew about infections. But in their laboratories, they could not seem to energize the immune cells to react to the infections. A link was missing, some cell in the immune-system soup that flipped the immune system cells on, and on in the right direction. They called the cells they were looking for "accessory cells." Steinman was working in the lab of the late Zanvil Cohn at Rockefeller University, an expert in the physiology of macrophages, which were considered to be a leading candidate for the missing accessory cells. "We looked at the populations [of cells] that were the source of the accessory cells," Steinman says. Using spleen tissue from mice.,"we found unusual cells that had never been seen before; they were tree-like in shape. Hence the name we gave them, dendritic, from the Greek word for tree." Exacting work Michel Nussenzweig was the first student to work with Steinman on dendritic cells, in 1977, shortly after the purification method for dendritic cells had been developed. He, Steinman and Cohn found that dendritic cells were very potent immune stimulators. Still, almost nobody believed dendritic cells were that special or significant, he says. For the next nearly 15 years, a good deal of the research published on dendritic cells came from Steinman and his colleagues. The cells are rare, making up less than one percent of white blood cells, and separating them out was an onerous process until Steinman and his colleagues devised a new method in the 1990s. "Once it became easy to work on the cells, then the field exploded, and there are now thousands of labs who study dendritic cells," Nussenzweig says. Steinman wasn’t afraid to argue that something so rare could be so important, says Antony Rosen, who worked in the Cohn lab with Steinman in the late 1980s and now is at Johns Hopkins University. "He was confident enough that it didn't matter to him that nobody had ever seen it before. It didn't matter to him that everybody rejected what he said. And he stayed at it and he knew he was right, and he proved that he was right." Vast potential Researchers are studying the properties of dendritic cells and how to control their activities for many potential uses. Helping dendritic cells to dampen immune response could ease symptoms of autoimmune disorders and allergies. Helping dendritic cells to boost immune response could help fight infections like AIDS and cancers. Steinman is currently concentrating his work on investigating and designing vaccines. "I just feel the vaccines we already have are medical miracles, but the scope and potential of new vaccines that target dendritic cells is just enormous," he says. "I also find that when I try to think about making a vaccine against HIV or against cancer, that I start asking some interesting scientific questions about how our immune systems operate." He also continues to call for research that aims to study science in people, to help people and to extend scientific understanding. "We need to build a new kind of research network, one that develops and supports researchers who can study the immune system in patients," he says. "I think the natural deductive instinct of most scientists is to keep figuring out how the cells work in simpler systems like mice, learn more about mechanism, and that's obviously going to be very productive. "But what I'd like to see is that we set our standards on the medical conditions that involve the immune system. I think that's where the biggest scientific challenges are, and if we don't direct ourselves to these conditions, we won't have the standards high enough for what we need to know." Part of that work is his role as a consultant for the Dana Foundation's immunology grants program, which targets patient-oriented research. Steinman has been a vociferous spokesman for such research, says Cooper at the University of Alabama. "He's just been unwavering in his insistence on trying to translate basic findings about how the immune system functions in a very basic way to see that that information gets translated into something that has relevance to people and their diseases." Of all the systems in the body, the immune system is the one "you can really teach, really make better," said Steinman during a forum at the Dana Center in 2006. But, he added, we don't yet know all the rules. Curiosity and collaboration The discovery of dendritic cells was a co-discovery, shared with Zanvil Cohn and other colleagues, Steinman says. He continues to collaborate, with colleagues at Rockefeller University and across the world. "He has been a mentor to a lot of people," says Madhav Dhodapkar, who worked in his lab a decade ago and now runs his own lab at Rockefeller. "People who haven't necessarily trained in his lab, I know, have benefited from interacting with him." Professionally, if one looks at how often his papers have been cited, thousands of times, it's easy to see how influential he is, says Rosen of Johns Hopkins. Most citations are for his work with dendritic cells, of course, but also for work on endocytosis and on basic cell biological progresses. "And some of those were classics in their time as well," he says. "He has this great knowledge of science, and it's like he's a child discovering something for the first time every time he reads it," Rosen says. "He's just got a hunger for it. That's why I think he made a big discovery." "He would come into the lab with a journal or with a paper that he thought you would be interested in, and he told you about it as if it were the coolest thing that he could ever have come across." It's a reciprocal pleasure, Steinman says. "I think young people, especially in a complex, intricate science like immunology, need support and discussion time. It's just too intricate to do everything yourself. They certainly reciprocate, and you know, the young, energetic mind has the best ideas." The two Lasker prizes for medical research, nicknamed "America's Nobels," are given each year. Steinman received the Lasker award for basic medical research. This year's award for clinical medical research was shared by Alain Carpentier and Albert Starr, who developed replacement heart valves.

Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden

Objective To examine the risk of neurological and autoimmune disorders of special interest in people vaccinated against pandemic influenza A (H1N1) with Pandemrix (GlaxoSmithKline, Middlesex, UK) compared with unvaccinated people over 8-10 months.
Design Retrospective cohort study linking individualised data on pandemic vaccinations to an inpatient and specialist database on healthcare utilisation in Stockholm county for follow-up during and after the pandemic period.
Setting Stockholm county, Sweden.
Population All people registered in Stockholm county on 1 October 2009 and who had lived in this region since 1 January 1998; 1 024 019 were vaccinated against H1N1 and 921 005 remained unvaccinated.
Main outcome measures Neurological and autoimmune diagnoses according to the European Medicines Agency strategy for monitoring of adverse events of special interest defined using ICD-10 codes for Guillain-Barré syndrome, Bell’s palsy, multiple sclerosis, polyneuropathy, anaesthesia or hypoaesthesia, paraesthesia, narcolepsy (added), and autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes; and short term mortality according to vaccination status.
Results Excess risks among vaccinated compared with unvaccinated people were of low magnitude for Bell’s palsy (hazard ratio 1.25, 95% confidence interval 1.06 to 1.48) and paraesthesia (1.11, 1.00 to 1.23) after adjustment for age, sex, socioeconomic status, and healthcare utilisation. Risks for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis remained unchanged. The risks of paraesthesia and inflammatory bowel disease among those vaccinated in the early phase (within 45 days from 1 October 2009) of the vaccination campaign were significantly increased; the risk being increased within the first six weeks after vaccination. Those vaccinated in the early phase were at a slightly reduced risk of death than those who were unvaccinated (0.94, 0.91 to 0.98), whereas those vaccinated in the late phase had an overall reduced mortality (0.68, 0.64 to 0.71). These associations could be real or explained, partly or entirely, by residual confounding.
Conclusions Results for the safety of Pandemrix over 8-10 months of follow-up were reassuring —notably, no change in the risk for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, or rheumatoid arthritis. Relative risks were significantly increased for Bell’s palsy, paraesthesia, and inflammatory bowel disease after vaccination, predominantly in the early phase of the vaccination campaign. Small numbers of children and adolescents with narcolepsy precluded any meaningful conclusions. 

Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer's Disease


Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline during middle to late adult life. The AD brain is characterized by deposition of amyloid β peptide (Aβ), which is produced from amyloid precursor protein by β- and γ-secretase (presenilin complex)-mediated sequential cleavage. Induced pluripotent stem (iPS) cells potentially provide an opportunity to generate a human cell-based model of AD that would be crucial for drug discovery as well as for investigating mechanisms of the disease.

Methodology/Principal Findings

(A) Time-dependent morphological changes of cells reseeded in a 24-well plate. Neuronal and glial cells were stained by anti-Tuj1 (left; red), anti-synapsin I (left; green), anti-MAP2 (right; red), and anti-GFAP (right; green) antibodies and DAPI (right; blue) at 38, 45, and 52 days. Scale bar, left; 20 µm, right; 50 µm. Expression levels of Tuj1 (B), synapsin I (C), MAP2 (D), and GFAP (E) at days 0, 24, 38, 45, and 52 were measured by qPCR and normalized by that of GAPDH. “Fold expression” is the ratio of expression at each day compared to day 0. Each point represents mean ± SD of 3 assays. *p<0.05, **p<0.01, ***p<0.001, significantly different from day 0 by Dunnett's test. (F–H) Neurotransmitter phenotypes at day 52. PAG (red)- and GAD (green)-positive (F), vGlut1 (green)- and Tuj1 (red)-positive (G), and GABA (green)- and Tuj1 (red)-positive cells (H). Blue, DAPI. Scale bar, 50 µm.
We differentiated human iPS (hiPS) cells into neuronal cells expressing the forebrain marker, Foxg1, and the neocortical markers, Cux1, Satb2, Ctip2, and Tbr1. The iPS cell-derived neuronal cells also expressed amyloid precursor protein, β-secretase, and γ-secretase components, and were capable of secreting Aβ into the conditioned media. Aβ production was inhibited by β-secretase inhibitor, γ-secretase inhibitor (GSI), and an NSAID; however, there were different susceptibilities to all three drugs between early and late differentiation stages. At the early differentiation stage, GSI treatment caused a fast increase at lower dose (Aβ surge) and drastic decline of Aβ production.


These results indicate that the hiPS cell-derived neuronal cells express functional β- and γ-secretases involved in Aβ production; however, anti-Aβ drug screening using these hiPS cell-derived neuronal cells requires sufficient neuronal differentiation.

Interferon β-1b–neutralizing antibodies 5 years after clinically isolated syndrome

The objective of this is study is to determine the frequency and consequences of neutralizing antibodies (NAbs) in patients with a first event suggestive of multiple sclerosis (MS) treated with interferon β-1b (IFNβ-1b).
In the Betaseron/Betaferon in Newly Emerging MS For Initial Treatment (BENEFIT) study, patients were randomly assigned to 250 μg IFNβ-1b (Betaferon) or placebo subcutaneously every other day for 2 years or until diagnosis of clinically definite MS (CDMS). Patients were then offered open-label IFNβ-1b for up to 5 years. NAb status was assessed every 6 months by the myxovirus protein A induction assay. A titer >20 NU/mL was considered NAb-positive, with low (≥20–100 NU/mL), medium (≥100–400 NU/mL), and high (≥400 NU/mL) titer categories. Here we examine early-treated patients, who received IFNβ-1b for up to 5 years.
NAbs were measured in 277 of 292 early-treated patients and detected at least once in 88 (31.8%) patients, with 53 (60.2%) reverting to NAb negativity by year 5. Time to CDMS, time to confirmed disability progression, and annualized relapse rate did not differ between NAb-positive and NAb-negative patients or between periods of NAb positivity vs NAb negativity within patients. Increases in newly active lesion number and T2 lesion volume and conversion to McDonald MS were associated with NAb positivity and were more pronounced with higher titers.

Table 1        Cross-sectional analyses for risk of CDMS, confirmed EDSS progression, and McDonald MS in NAb negative vs eventually NAb positive patients with 2 consecutively positive NAb measurements

Risk of event

HR (95% CI)
p Value
EDSS progression
HR (95% CI)
p Value
McDonald MS
HR (95% CI)
p Value
Positive (≥20 NU/mL) vs negative
0.77 (0.05–1.18)
p = 0.24
0.88 (0.50–1.54)
p = 0.28
1.54 (1.15–2.08)
p = 0.0044
Single model
Low titer (20–100 NU/mL) vs negative
0.73 (0.41–1.31)
p = 0.29
1.05 (0.51–2.15)
p = 0.99
1.41 (0.94–2.12)
p = 0.09
Medium titer (100–400 NU/mL) vs negative
0.91 (0.46–1.82)
p = 0.80
0.57 (0.18–1.83)
p = 0.34
1.71 (1.10–2.77)
p = 0.03
High titer (≥400 NU/mL) vs negative
0.71 (0.32–1.56)
p = 0.39
0.91 (0.05–1.18)
p = 0.85
1.62 (0.99–2.65)
p = 0.06
Abbreviations: CDMS = clinically definite multiple sclerosis; EDSS = expanded disability status scale; NAb = neutralizing antibody; HR = hazard ratio, CI = confidence interval.
*By Cox proportional hazards regression adjusted for age, gender, number of T2/gadolinium-enhancing lesions, mono-/multifocal presentation, and use of steroids at the time of a first clinical event suggestive of MS. Hazard ratios above 1.0 indicate increased risk.

In conclusion, although NAb positivity was associated with increased brain MRI activity, no discernible effects on clinical outcomes were found. This finding may reflect the greater power of MRI compared with clinical outcomes to detect the treatment effects of IFNβ-1b and may also result from temporal changes in NAb titers and biology.

Immunotherapy for Alzheimer's Disease: Rational Basis in Ongoing Clinical Trials

Amyloid-β (Aβ) immunotherapy has recently begun to gain considerable attention as a potentially promising therapeutic approach to reducing the levels of Aβ in the Central Nervous System (CNS) of patients with Alzheimer's Disease (AD). Despite extensive preclinical evidence showing that immunization with Aβ(1-42) peptide can prevent or reverse the development of the neuropathological hallmarks of AD, in 2002, the clinical trial of AN-1792, the first trial involving an AD vaccine, was discontinued at Phase II when a subset of patients immunized with Aβ(1-42) developed meningoencephalitis, thereby making it necessary to take a more refined and strategic approach towards developing novel Aβ immunotherapy strategies by first constructing a safe and effective vaccine.
This review describes the rational basis in modern clinical trials that have been designed to overcome the many challenges and known hurdles inherent to the search for effective AD immunotherapies. The precise delimitation of the most appropriate targets for AD vaccination remains a major point of discussion and emphasizes the need to target antigens in proteins involved in the early steps of the amyloid cascade. Other obstacles that have been clearly defined include the need to avoid unwanted anti-Aβ/APP Th1 immune responses, the need to achieve adequate responses to vaccination in the elderly and the need for precise monitoring.
Proposed mechanisms of action of immunotherapy in amyloid reduction. Panel A describes the mechanism of microglial phagocytosis. Amyloid fibers opsonized by antibodies enter the brain from the bloodstream where microglial cells recognize the antibodies and phagocytose the amyloid via the Fcg receptor. Panel B represents the mechanism of catalytic disaggregation. Amyloid fibers are bound by antibodies that disrupt the tertiary structure of the amyloid deposit. This results in solubilization of the Ab and exit of the brain. Panel C shows the peripheral sink mechanism. In this case, monomeric soluble Ab circulating in the bloodstream is bound by the circulating antibodies. This sequestration of circulating Ab produces a shift in the concentration gradient of Ab between the brain and the blood causing an efflux of Ab out of the brain.

Molecular basis of active and passive immunization. A. Vaccination (active immunization) activates the body’s immune system to produce antigen-specific antibodies. In AD, full-length Aβ or a fragment of Aβ conjugated to a foreign T cell epitope carrier protein can be used as an antigen, which is delivered into the body along with an immune system booster (adjuvant). The humoral immune response is generated when APCs, which internalize and process the antigen, present T cell epitopes to naive Th lymphocytes. Binding of co-stimulatory molecules on the surfaces of APCs and T cells provides a secondary signal that enhances T cell activation. Meanwhile, the soluble antigen binds to B cell receptors via the B cell epitope, and this antigen is presented to activated T cells to help the B cell make antibodies against the antigen. Activated T cells also produce cellular immune responses. A Th1 cellular immune response leads to the release of pro-inflammatory cytokines, whereas a Th2 response causes release of anti-inflammatory cytokines. b. Passive immunization bypasses the need activate the immune system to initiate an immune response to produce antigen-specific antibodies. In both active and passive Aβ immunization, anti-Aβ antibodies bind Aβ, targeting the peptide for clearance. Abbreviations: Aβ, amyloid-β; APC, antigen presenting cell 
Schematic representation of the two types of immunotherapy for Alzheimer's disease used on experimental animal models. Panel A describes active immunization. Fibrillar Ab142 is combined with an adjuvant by emulsification and the product of the reaction is then injected into the mouse. The mouse produces anti-Ab antibodies in response to the vaccination. Panel B describes passive immunization. In this case, mice are immunized with Ab as with active immunization. Hybridomas are then produced and selected for optimal antibody properties. The antibodies are then harvested, purified and administered to another mouse for treatment. 

Novel strategies have been implemented to overcome these problems including the use of N-terminal peptides as antigens, the development of DNA based epitope vaccines and vaccines based on passive immunotherapy, recruitment of patients at earlier stages with support of novel biomarkers, the use of new adjuvants, the use of foreign T cell epitopes and viral-like particles and adopting new efficacy endpoints. These strategies are currently being tested in over 10,000 patients enrolled in one of the more than 40 ongoing clinical trials, most of which are expected to report final results within two years.

Ongoing clinical trials based on active or passive immunotherapy for AD. 
Phase II/IIa/IIb
ACC-001 is a short amino-terminal Aβ (1-6) fragment that is derived from the N-terminal B cell epitope of Aβ while avoiding T cell activation. Antibodies specific for this Aβ peptide can cross the blood-brain barrier and act directly in the central nervous system to induce plaque clearance. Note: this trial was temporarily suspended due to   vasculitis detected in one patient.
Phase II
CAD-105 is Aβ1–5 coupled to Qb virus-like particles. Antibodies specific for this Aβ peptide can cross the blood-brain barrier and act directly in the central nervous system to induce plaque clearance.
Phase I
V950 is an Aβ amino-terminal peptide conjugated to ISCO-MATRIX®.
Phase I
UB311 uses the peptide Aβ1–14 with UBITh®. The UBITh AD immunotherapeutic vaccine has been engineered to elicit anti-N-terminal Aβ (1-14) antibodies while minimizing potential for the generation of adverse anti-Aβ immune responses. The vaccine has been further designed for minimization of inflammatory responses through the use of a proprietary vaccine delivery system that favors Th2 type regulatory T cell responses over Th1 pro-inflammatory T cell responses.
Affitope AD02  / Mimotope Aβ(1-6)
Phase II/IIa/IIb
Affitope AD02 is a short amino-terminal Aβ fragment (Aβ1-6) that is derived from the N-terminal B cell epitope of Aβ while avoiding T cell activation.
AAB-001 / Bapineuzumab
Phase III
Bapineuzumab is an anti-Aβ antibody that binds specifically to soluble amyloid-β and therefore may act to draw the peptide away from the brain through the blood to be cleared in the periphery.
Phase II/IIa/IIb
CAD106 is a vaccine based on an epitope that contains multiple copies of the Aβ 1-6 peptide, that avoids T cell activation, coupled to the Qβ virus-like particle.
Intravenous Immunoglobulin /Gammagard, IVIg
Phase III
Intravenous Immunoglobulin (IVIg) is obtained from the pooled plasma of healthy human blood donors, and contains natural anti-amyloid antibodies. In vitro data have demonstrated that human anti-Aβ antibodies inhibit fibril formation and diminish neurotoxicity.
Phase I
MABT5102A is a humanized monoclonal antibody that binds Aβ.
Solanezumab  / LY2062430
Phase III
Solanezumab binds specifically to soluble amyloid-β and therefore may act to draw the peptide away from the brain to be cleared in the periphery.
Phase II
Multiple IV Dose Study of anti-Aβ mAb in patients with mild To moderate AD. PF-04360365 binds to Aβ.
Phase II
R1450 is a fully humanized monoclonal antibody that binds Aβ.
Phase I
Anti-Aβ antibody that binds .

Summary of the main strategies and rational to overcome the challenges raised from the AN1792 clinical trial:

Challenge: Unwanted anti-Aβ/APP Th1 immune responses
Using N terminal peptide (Ab1–15) as antigen
The Ab1–15 peptide is the major B cell epitope. Antibodies raised to amino acids 1–11, 1–7, and 1–5 of Ab42 bind to b-amyloid plaques with higher affinity and initiate immune responses much stronger than antibodies raised to amino acids 3–7, 5–11, and 11–26. The smallest domain in the Ab peptide to which the antibodies bind with high affinity is that encoding amino acids 4-10.
Using DNA based epitopes
DNA-based vaccination induces prolonged, endogenous antigen synthesis and processing within the subject’s own cells infected with virus encoding the desired epitopes and adjuvants.
Adjuvants facilitate the internalization of antigen into the antigen presenting cells to enhance the efficiency of processing and presentation of the antigens.
Using new adjuvants
Mannan is as a potentially optimal molecular adjuvant due to its ability to enhance both B- and T-cell immune responses. This adjuvant has the advantage of inducing a Th2 rather than Th1 response

Using passive immunotherapy
Vaccines  using monoclonal antibodies or Immunoglobulins do not show adverse reactions related to cellular immunity
Challenge: The need of early treatment
Early diagnosis with support of biomarkers
Repeated vaccination at regular intervals since early stages would increase the probability of a good response before the toxic forms of β-amyloid begin to accumulate.
Challenge: Hypo-responsiveness to vaccines in the elderly
Recruiting previously generated memory T cells
A vaccine based on Ab peptide fused with Th epitopes from conventional vaccines or common pathogens produced during childhood vaccination or during prior exposure to human pathogens could potentially induce a rapid expansion of pre-existing memory T cells and their differentiation into effector T cells
Using Foreign T cell epitope

Foreign T cell epitopes as synthetic, non-natural Pan HLA DR-binding epitopes produce more potent responses on a molar basis than a tetanus-derived universal epitope.
Using Viral-like particles
Incorporation of the Ab B cell epitope into a viral capsid protein allows the expression of this epitope on the surface of VLP in a repetitive and ordered array. Such organization of the epitope may induce T cell-independent B cell activation and production of high titers of anti-Ab antibodies
Challenge: The need of more precise monitoring
Adopting new efficacy endpoints
Besides traditional endpoints, new clinical endpoints such as neuroimaging and biomarkers provide a more detailed picture of basal status and response of the patients.

Published at: Curr Pharm Des. 2011 Mar 4

Dr Frank Longo discusses exciting MS research results

Stanford Department of Neurology and Neurosciences Chair Frank Longo talks about the groundbreaking Multiple Sclerosis research of Stanford scientist Lawrence Steinman.