MEET US AT The 16th Naples Workshop on Bioactive Peptides
The 16th Naples Workshop on Bioactive Peptides will take place on June 7-9, 2018 in Naples (Italy) at the Centro Congressi “Federico II”. Participants will share the latest developments and future directions of peptide science and relevant applications of peptides in life science.
Six sessions with plenary lectures, key notes and oral presentations and two poster sessions are scheduled. A peptide showcase will give the opportunity to companies developing peptide therapeutics and related technologies to present their perspectives on the current and future strategies. Do not miss the Bachem Peptide Showcase “Acetylation in Fmoc SPPS – Benefits and Drawbacks” presented by Dr. Carolin Lechner, R&D Department, Bachem AG.
Bachem supports its customers in the pursuit of groundbreaking discoveries that further scientific advances, particularly in the field of medicine. A comprehensive catalog of biochemicals deliverable ex-stock, an exclusive custom syntheses service for research labs and a full range of services to the pharma and biotech industries complete our service portfolio. Dr. Stephanie Henriot, Research Chemicals Department at Bachem AG, is excited to meet with our customers, learn their needs for peptides and discuss how Bachem can help to advance their research.
We look forward to meeting you at the Naples Workshop 2018!
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system in which focal lymphocytic infiltration leads to damage of myelin and axons.
The pathologic hallmark of MS is multiple focal areas of myelin loss within the CNS called plaques or lesions. These lesions most commonly affect the white matter in the optic nerve, brain stem, basal ganglia, and spinal cord, or white matter tracts close to the lateral ventricles and can be detected by magnetic resonance imaging (MRI). The peripheral nervous system is rarely involved.
It is thought that worldwide more than 2.3 million people are affected by this disease. MS is typically diagnosed between ages 20 to 50. It affects two to three times as many women as men and is more common in Caucasians of northern European ancestry. MS signs and symptoms may differ from person to person and over the course of the disease. They may include fatigue, numbness or tingling, walking (gait) difficulties, weakness, dizziness and vertigo, bladder problems, sexual problems, bowel problems, pain, and cognitive changes.
Several types or disease courses have been defined
• Clinically Isolated Syndrome (CIS)
• Relapsing-remitting MS (RRMS)
• Primary progressive MS (PPMS)
• Secondary progressive MS (SPMS)
CIS is a first episode of neurologic symptoms caused by inflammation and demyelination in the CNS. 30% to 70% of persons experiencing CIS later develop MS.
RRMS is the most common disease course. It is characterized by clearly defined attacks of new or increasing neurological symptoms (relapses) followed by periods of partial or complete recovery (remissions). Approximately 85% of people with MS are initially diagnosed with RRMS.
PPMS is characterized by progression of disability from the onset of symptoms, without early relapses or remissions. It occurs in approximately 15% to 20% of individuals. The usual age of onset for PPMS is later than that of RRMS.
SPMS follows an initial relapsing-remitting course. Approximately 65% of those who are diagnosed with RRMS will eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function over time.
Diagnosis of MS is based on a careful medical history, a neurologic exam and various tests including magnetic resonance imaging, evoked potentials and spinal fluid analysis in order to rule out other medical problems with similar signs and symptoms.
Treatment of Multiple Sclerosis
MS is not a curable disease but current therapies can modify or slow the disease course and manage symptoms. Several disease-modifying medications to treat relapsing forms of MS are available. They reduce the frequency and severity of relapses and reduce the accumulation of lesions in the CNS.
|Corticosteroids||Anti-inflammatory / immunosuppressive||Acute exacerbations|
(interferon beta-1a, interferon beta-1b)
|Interferon beta directly increases expression and concentration of anti-inflammatory agents while downregulating the expression of pro-inflammatory cytokines.||First-line treatment in relapsing forms of MS|
|Glatiramer||Immunoactive mixture of synthetic polypeptides composed of four amino acids resembling myelin basic protein (MBP).||Relapsing forms of MS|
|Natalizumab||Humanized monoclonal antibody against the cell adhesion molecule α4-integrin. Natalizumab appears to reduce the transmission of immune cells into the CNS by interfering with the α4β1-integrin receptor molecules on the surfaces of cells.||Relapsing forms of MS|
|Alemtuzumab||Humanized therapeutic monoclonal antibody that binds to CD52, a cell-surface antigen present on T and B cells. Alemtuzumab depletes circulating T and B cells through antibody-dependent cellular cytolysis and complement-mediated lysis.||Relapsing forms of MS|
|Ocrelizumab||Humanized anti-CD20 antibody. Ocrelizumab targets mature B cells.||Relapsing forms of MS, early primary progressive MS|
|Dimethyl fumarate||Anti-inflammatory / cytoprotective||Relapsing forms of MS|
|Fingolimod||Prodrug. Its active metabolite fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator. The mechanism by which fingolimod exerts therapeutic effects may involve reduction of lymphocyte migration into the CNS.||Relapsing forms of MS|
|Teriflunomide||Immunomodulatory drug inhibiting pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase.||Relapsing forms of MS|
Animal Models of Multiple Sclerosis
Several established experimental animal models of MS have been described. These include immune-mediated, virus induced, and toxin induced models. They have been proven useful for studying different aspects of inflammation, demyelination, remyelination, and neurodegeneration in the CNS.
In toxin induced models, agents such as the intercalating substance ethidium bromide, the detergent lysolecithin, and the chopper-chelator cuprizone are used to induce experimental demyelination. These models have proven useful for studying remyelination processes in animals.
Animal models that involve virus-induced demyelination are generated by Theiler’s virus, canine distemper virus, and mouse hepatitis virus. The best-characterized is the Theiler’s virus model. It induces inflammatory demyelinating disease, which in many aspects reflects the disease in MS.
Experimental autoimmune encephalitis (EAE) is one of the most studied animal models of MS. It can be induced by active immunization with myelin peptides or by the adoptive transfer of myelin-specific T cells resulting in inflammatory infiltrates and demyelination in the CNS. In actively induced EAE animals (e.g. mice, rats) are subcutaneously immunized with a myelin-related peptide emulsified in complete Freund’s adjuvant. In mice, an additional adjuvant, pertussis toxin, is necessary for active EAE. Although the precise effect of pertussis toxin is unknown, it has been suggested that this microbial product promotes EAE by facilitating the migration of pathogenic T cells to the CNS as well as to promote proliferation and cytokine production by T cells and break T cell tolerance. Immune-driven demyelinating models have become standard for pre-clinical screening of candidate MS therapies.
|Product Number||Product Name||Sequence||Product Description||References|
|4003264||Experimental Allergic Encephalitogenic Peptide (human)||H-Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Arg-OH||Active fragment of the myelin basic protein. By a cell-mediated immune response, the peptide causes experimental allergic encephalomyelitis, which is an inflammatory demyelinating disease of the CNS.||R.Shapira et al., Science, 178, 736 (1971) F.C.Westall et al., Nature, 229, 22 (1971)|
|4026109||MHC Class II IA β Chain (58-75)||Ac-Ala-Glu-Tyr-Tyr-Asn-Lys-Gln-Tyr-Leu-Glu-Gln-Thr-Arg-Ala-Glu-Leu-Asp-Thr-NH₂||Vaccination of mice with this synthetic peptide from the third hypervariable region of the murine class II MHC IAS β chain resulted in the prevention and treatment of experimental autoimmune encephalomyelitis, a T cell mediated, demyelinating disease of the CNS that represents a model for human MS.||D.J.Topham et al., Proc. Natl. Acad. Sci. USA, 91, 8005 (1994)|
|4016649||Myelin Basic Protein (4-14)||H-Gln-Lys-Arg-Pro-Ser-Gln-Arg-Ser-Lys-Tyr-Leu-OH||This fragment of the bovine myelin basic protein (residues 4-14) has been described as the most specific substrate for the selective assay of protein kinase C. Its Km value of 7 µM is comparable with the values for H1 histone and intact myelin basic protein, but its velocity of phosphorylation is twice as fast.||J.P.McKenna et al., Inflamm. Res., 44, 66 (1995) T.Nanmori et al., Biochem. Biophys. Res. Commun., 203, 311 (1994) B.Stauble et al., Biochem. Mol. Biol. Int., 29, 203 (1993) I.Yasuda et al., Biochem. Biophys. Res. Commun., 166, 1220 (1990)|
|4012638||(Des-Gly⁷⁷,Des-His⁷⁸)-Myelin Basic Protein (68-84) (guinea pig)||H-Tyr-Gly-Ser-Leu-Pro-Gln-Lys-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-OH||M.D.Mannie et al., Proc. Natl. Acad. Sci. USA, 82, 5515 (1985) E.H.Eylar et al., J. Biol. Chem., 246, 5770 (1971)|
|4028466||Myelin Basic Protein (83-99) (bovine) trifluoroacetate salt||H-Glu-Asn-Pro-Val-Val-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro-OH trifluoroacetate salt||MBP (83-99) corresponds to the immunodominant region of myelin basic protein restricted by HLA-DR2, the HLA class II haplotype with the strongest association to MS. T cell responses against this part of the MBP molecule represent a potential therapeutic target in MS.||J.Hong et al., Eur. J. Immunol., 34, 870 (2004) B.Bielekova et al., Nat. Med., 6, 1167 (2000) B.Hemmer et al., Neurology, 49, 1116 (1997)|
|4049448||Myelin Basic Protein (85-99) Peptide Antagonist trifluoroacetate salt||H-Glu-Lys-Pro-Lys-Val-Glu-Ala-Tyr-Lys-Ala-Ala-Ala-Ala-Pro-Ala-OH trifluoroacetate salt||The peptide EKPKVEAYKAAAAPA competes with MBP (85-99), a major candidate autoantigen in MS, for binding to human leukocyte antigen (HLA)-DR2. The peptide also inhibits IL-2 secretion by MBP (85-99) specific T-cell clones and induces the production of Th2 cytokines by splenocytes. Furthermore, it could be shown that the peptide is able to suppress experimental autoimmune encephalomyelitis (EAE) in several models in a manner that is equipotent to random amino acid copolymers, such as Copaxone [poly (Y,E,A,K)n].||J.N.H.Stern et al., Proc. Natl. Acad. Sci. USA, 102, 1620 (2005)|
|4025349||Myelin Basic Protein (87-99) (human, bovine, rat)||H-Val-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro-OH||This MBP fragment has been shown to induce the proliferation of an encephalitogenic, myelin basic protein-specific T cell line. Active immunization of rats with this peptide induced acute experimental autoimmune encephalomyelitis. This protein region is highly conserved among mammalian species.||R.E.Jones et al., J. Neuroimmunol., 37, 203 (1992)|
|4042037||Myelin Oligodendrocyte Glycoprotein (35-55) (human) trifluoroacetate salt||H-Met-Glu-Val-Gly-Trp-Tyr-Arg-Pro-Pro-Phe-Ser-Arg-Val-Val-His-Leu-Tyr-Arg-Asn-Gly-Lys-OH trifluoroacetate salt||In contrast to the encephalitogenic rat homolog, myelin oligodendrocyte glycoprotein (35-55) (human) does not appear to be a major T-cell epitope in MS propably due to its lower amount of helical structure formed when dissolved in micellar sodium dodecyl sulfate, a membrane mimicking solvent.||M.F.Mesleh et al., Neurobiol. Dis., 9, 160 (2002)
S.Albouz-Abo et al., Eur. J. Biochem., 246, 59 (1997)
N.Kerlero de Rosbo et al., Eur. J. Immunol., 27, 3059 (1997)
|4028291||Myelin Oligodendrocyte Glycoprotein (35-55) (mouse, rat) trifluoroacetate salt||H-Met-Glu-Val-Gly-Trp-Tyr-Arg-Ser-Pro-Phe-Ser-Arg-Val-Val-His-Leu-Tyr-Arg-Asn-Gly-Lys-OH trifluoroacetate salt||MOG peptide (35-55) is highly encephalitogenic and can induce strong T and B cell responses. A single injection of this peptide produces a relapsing-remitting neurologic disease with extensive plaque-like demyelination. Because of the clinical, histopathologic, and immunologic similarities with MS, this MOG-induced demyelinating encephalomyelitis may serve as a model for investigating MS.||J.Liu et al., Nat. Med., 4, 78 (1998)
M.Ichikawa et al., J. Immunol., 157, 919 (1996)
|4041119||Myelin Oligodendrocyte Glycoprotein (35-55) amide (rat, mouse) trifluoroacetate salt||H-Met-Glu-Val-Gly-Trp-Tyr-Arg-Ser-Pro-Phe-Ser-Arg-Val-Val-His-Leu-Tyr-Arg-Asn-Gly-Lys-NH₂ trifluoroacetate salt||F.Puentes et al., J. Neuroinflammation, 10, 118 (2013)|
|4037126||Myelin Proteolipid Protein (139-151) (depalmitoylated) (human, bovine, dog, mouse, rat) trifluoroacetate salt||H-His-Cys-Leu-Gly-Lys-Trp-Leu-Gly-His-Pro-Asp-Lys-Phe-OH trifluoroacetate salt||Strongly antigenic peptide for inducing autoimmune encephalomyelitis in mice for studying MS.||S.Youssef et al., Nature, 420, 78 (2002)|
|4030575||(Ser¹⁴⁰)-Myelin Proteolipid Protein (139-151) (depalmitoylated) (human, bovine, dog, mouse, rat) trifluoroacetate salt||H-His-Ser-Leu-Gly-Lys-Trp-Leu-Gly-His-Pro-Asp-Lys-Phe-OH trifluoroacetate salt||This fragment of myelin proteolipid protein is an encephalitogenic determinant, able to bind to diverse sets of T cell receptors.||H.Waldner et al., Proc. Natl. Acad. Sci. USA, 97, 3412 (2000)
V.K.Kuchroo et al., J. Immunol., 153, 3326 (1994)
V.K.Tuohy et al., J. Immunol., 142, 1523 (1989)
|4031176||H-Ala-Pro-Arg-Thr-Pro-Gly-Gly-Arg-Arg-OH trifluoroacetate salt||The peptide APRTPGGRR contains a consensus sequence for substrate recognition by the meiosis-activated myelin basic protein kinase (p44 mpk) and can be used as substrate for p44 mpk.||I.Clark-Lewis et al., J. Biol. Chem., 266, 15180 (1991)|
|4015304||H-Gly-Arg-Gly-Leu-Ser-Leu-Ser-Arg-OH||The sequence GRGLSLSR corresponds to human myelin basic protein 106-113. It is a substrate for cAMP-dependent protein kinase.||L.Timchenko et al., Proc. Natl. Acad. Sci. USA, 92, 5366 (1995)
P.Daile et al., Nature, 257, 416 (1975)
|4031127||H-Lys-Arg-Glu-Leu-Val-Glu-Pro-Leu-Thr-Pro-Ser-Gly-Glu-Ala-Pro-Asn-Gln-Ala-Leu-Leu-Arg-OH||T669 peptide is a substrate for the ERT protein kinase. The ERT protein kinase is a growth factor-stimulated protein kinase that phosphorylates the epidermal growth factor receptor at Thr⁶⁶⁹.||J.K.Klarlund et al., J. Biol. Chem., 268, 7646 (1993)
E.Alvarez et al., J. Biol. Chem., 266, 15277 (1991)
Explore our MS-related products in our online shop.
National Multiple Sclerosis Society
I. Bjelobaba, V. Begovic-Kupresanin, S. Pekovic, I. Lavrnja, Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis. J. Neurosci. Res. 2018, 1-22.
H. Lassmann and M. Bradl, Multiple sclerosis: experimental models and reality. Acta Neuropathol. 2017, 133, 223-244.
A.Ebringer, Multiple Sclerosis, Mad Cow Disease and Acinetobacter. Springer eBooks 2015
E. Kingwell, J.J. Marriott, N. Jette, T. Pringsheim, N. Makhani, S.A. Morrow et al, Incidence and prevalence of multiple sclerosis in Europe: a systematic review. BMC Neurol. 2013, 13, 128.
B.F. Popescu, I. Pirko, C.F. Lucchinetti, Pathology of multiple sclerosis: where do we stand? Continuum (Minneap. Minn.) 2013, 19, 901-921.
A. Compston and A. Coles, Multiple sclerosis. Lancet 2008, 372, 1502-1517.
D. Miller, F. Barkhof, X. Montalban, A. Thompson, M. Filippi, Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. The Lancet Neurology 2005, 4, 281-288.
H. Waldner, M. Collins, V.K. Kuchroo, Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease. J. Clin. Invest. 2004, 113, 990-997.
PEPTIDE THERAPEUTICS IN CLINICAL DEVELOPMENT FOR MULTIPLE SCLEROSIS
Multiple sclerosis (MS) is a progressive autoimmune disease that has a significant impact on quality of life and affects an estimated 2.5 million people worldwide (1). There is no curative treatment for MS and there is a great need for treatment options to slow down or prevent progression of the disease. In addition, there is increasing interest in developing oral therapies to provide options that are more convenient for patients. There are currently 15 disease modifying drugs approved by the U.S. Food and Drug Administration for the treatment of MS including the blockbuster Copaxone® (glatiramer acetate), an injectable peptide-based drug (2). The MS drug pipeline is robust and as shown in Table 3, there are several peptide-based drug candidates advancing through clinical development for the treatment of different forms of MS.
|Product Name||Active Ingredient||Condition Treated||Highest Phase||Company Name|
|ATX-MS-1467||Relapsing Remitting Multiple Sclerosis (RRMS), Secondary Progressive Multiple Sclerosis (SPMS)||Phase II||Apitope International NV|
|Glatiramer acetate depot||glatiramer acetate||Primary Progressive Multiple Sclerosis (PPMS), Relapsing Remitting Multiple Sclerosis (RRMS)||Phase II||Mapi Pharma Ltd.|
|GM-6||Alzheimer's Disease, Multiple Sclerosis, Parkinson's Disease, Acute Ischemic Stroke, Huntington’s Disease, Amyotrophic Lateral Sclerosis||Phase II||Genervon Biopharmaceuticals LLC|
|RPI-78M||Multiple Sclerosis, Human Immunodeficiency Virus (HIV) Infections (AIDS), Simplexvirus (HSV) Infections, Herpes Zoster (Shingles), Adrenoleukodystrophy (Adrenomyeloneuropathy/ Schilder-Addison Complex)||Phase II||ReceptoPharm Inc.|
|SMderpept||Relapsing Remitting Multiple Sclerosis (RRMS)||Phase II||Centrum Neurologii Krzysztof Selmaj|
|NA-831||traneurocin||Alzheimer's Disease, Multiple Sclerosis, Stroke||Phase I||NeuroActiva Inc.|
Phase II Candidates
Apitope International NV is developing a vaccine, ATX-MS-1467, for the treatment of MS. The vaccine contains four peptides derived from myelin basic protein, an autoantigen in MS. In 2017, the company reported positive results from a Phase IIa study of ATX-MS-1467 in patients with relapsing MS (1).
Mapi Pharma Ltd. is developing glatiramer acetate depot, a once-monthly long-acting formulation of glatiramer acetate, for the treatment of relapsing remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). In 2018, Mapi Pharma announced the completion of a Phase II clinical trial of glatiramer acetate depot and the company intends to submit an IND to the U.S. Food and Drug Administration for a pivotal Phase III trial. In addition, the company is planning a Phase IIa clinical trial to evaluate the safety and efficacy of glatiramer acetate depot in patients with PPMS (3).
GM-6, a six amino acid analog of motoneuronotrophic factor (MNTF), is under development by Genervon Biopharmaceuticals LLC for several indications including Alzheimer’s disease, MS, Parkinson’s disease, acute ischemic stroke, Huntington’s disease and amyotrophic lateral sclerosis (3). In 2018, Genervon announced that the company is planning Phase III clinical trials of GM-6 for amyotrophic lateral sclerosis and Phase II trials for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and MS (4).
ReceptoPharm Inc. is developing RPI-78M, a chemically modified α-cobratoxin, as a candidate to treat MS and other neurological disorders. RPI-78M contains anti-cholinergic peptides that block the action of acetylcholine at nicotinic acetylcholine receptors (3). This candidate can be administered through injection or orally so it may provide an additional quality of life benefit for patients. RPI-78M is in Phase II clinical trials for the treatment of MS. In 2015, Nutra Pharma, ReceptoPharm’s parent company, announced that they received Orphan Designation from the U.S. Food and Drug Administration for RPI-78M for the treatment of MS in children (1).
SMderpept, a peptide mixture, is under development by Centrum Neurologii Krzysztof Selmaj for the treatment of RRMS. The peptide mixture consists of Myelin Basic Protein (MBP) 85-99, Myelin Oligodendrocyte Glycoprotein (MOG) 35-55 and Myelin Proteolipid Protein (PLP) 139-151. In 2016, Centrum Neurologii Krzysztof Selmaj registered a Phase II trial with the European Registry of Clinical Trials. The purpose of the study is to show that SMderpept reduces the amount of relapses compared to treatment with interferon β-1A (3).
Phase I Candidates
NeuroActiva Inc., formerly Bioneuromed, is developing NA-831 (traneurocin) for the treatment of Alzheimer’s disease, MS and stroke. The product candidate utilizes the MICROS controlled release infusion system (3). NeuroActiva plans to conduct a Phase IIb clinical trial of NA-831 in Alzheimer’s disease in 2018 (5).
There are several new drugs on the horizon for the treatment of patients with MS. To support researchers and organizations studying MS and developing new treatments for this disease, Bachem offers a selection of peptides such as MOG, MBP and PLP peptides. In addition, Bachem offers a comprehensive custom peptide synthesis service and the production of new chemical entities to assist companies with developing peptide-based therapeutics.
(1) Medtrack (2018)
(2) Medications, National Multiple Sclerosis Society (2018)
(3) GlobalData (2018)
(4) Genervon Presents Innovative CNS Drug Candidate at 2018 BIO CEO & Investor Conference, Genervon (2018)
(5) Products, NeuroActiva (2018)
MEET BACHEM: BO HEINZ
What is your official job title at Bachem?
Research Sales Manager
How long have you been with Bachem?
I have worked for Bachem for roughly one year.
Briefly, what do you do at Bachem?
My function at Bachem is actively sell our research products and services in order to meet established goals and business forecasts.
What is your academic background/degrees or training?
I have a Master’s Degree in Molecular Bioengineering from TU Dresden, Germany.
What do you like to do outside of work?
I am currently training for a half marathon and I enjoy playing guitar and spending time with friends and family.
How is the Marketing & Sales team partnering with their customers?
We believe in developing a strong partnership right at the start of our Bachem 360 degree model, whereby my team is supporting the basic research of today, for the future development of tomorrow.
What makes a perfect day for you?
Something about a sandy beach in sunny Los Angeles always sounds perfect.
What is your business motto?
Your attitude, not your aptitude, will determine your altitude!
What do you like most about your job?
Besides my work I very much like my team.
Thank you very much Bo.
Interesting news about peptides in basic research and pharmaceutical development:
Artificial antimicrobial peptides could help overcome drug-resistant bacteria-MIT
Peptide-based biogenic dental product may cure cavities-University of Washington
Novel drug shows promise against acute myeloid leukemia-EurekAlert!
Blocking matrix-forming protein might prevent heart failure-Cincinnati Children’s
Bachem peptides and biochemicals are widely cited in research publications. Congratulations to all our customers with recent publications!
M. Gonzalez-Gronow et al.
Myelin basic protein stimulates plasminogen activation via tissue plasminogen activator following binding to independent l-lysine-containing domains.
Biochemical and Biophysical Research Communications 490, 855-860 (2017)
F. Luo et al.
Inhibition of Drp1 hyper-activation is protective in animal models of experimental multiple sclerosis.
Experimental Neurology 292, 21-34 (2017)
L. Stolz et al.
Anticoagulation with warfarin and rivaroxaban ameliorates experimental autoimmune encephalomyelitis.
Journal of Neuroinflammation 14, 152 (2017)
R.A. LaMothe et al.
Tolerogenic nanoparticles induce antigen-specific regulatory T cells and provide therapeutic efficacy and transferrable tolerance against experimental autoimmune encephalomyelitis.
Frontiers in Immunology. 9, 281 (2018)
N.M.J. Rupniak et al.
NK2 and NK1 receptor-mediated effects of NKA and analogs on colon, bladder, and arterial pressure in anesthetized dogs.
Naunyn-Schmiedeberg’s Archives of Pharmacology 391, 299-308 (2018)