Jochen C Ulzheimer

Publications of Jochen C Ulzheimer

• Therapeutic approaches to multiple sclerosis: an update on failed, interrupted, or inconclusive trials of neuroprotective and alternative treatment strategies.

  Authors: Sven G Meuth, Stefan Bittner, Jochen C Ulzheimer, Christoph Kleinschnitz, Bernd C Kieseier, Heinz Wiendl

  BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. 10/2010; 24(5):317-30.

  Currently approved multiple sclerosis (MS) therapeutics have a mainly anti-inflammatory mode of action. However, a number of promising clinical trials have been initiated that either focus onCurrently approved multiple sclerosis (MS) therapeutics have a mainly anti-inflammatory mode of action. However, a number of promising clinical trials have been initiated that either focus on neuroprotection or follow completely different treatment strategies. So far, all of these clinical trials have failed to show efficacy or had to be halted prematurely because of unexpected adverse events. Some others show results that are of unknown significance with regard to a reliable assessment of true efficacy versus safety. For example, trials addressing the highly promising sodium channel blockers are under close observation because of potential adverse effects after drug withdrawal. Previously failed therapeutic approaches in MS have indicated that there are discrepancies between the theoretical expectations and practical outcomes of different compounds. Learning from these failures helps to optimize future study designs and to reduce risks to patients. This review summarizes trials on MS treatments since 2001 that failed or were interrupted, attempts to analyze the underlying reasons for failure, and discusses the implications for our current view of MS pathogenesis, clinical practice, and the design of future studies. In order to maintain clarity, this review focuses on neuroprotective and various other treatment strategies. Clinical trials addressing anti-inflammatory research strategies are presented elsewhere.

• Therapeutic approaches to multiple sclerosis: an update on failed, interrupted, or inconclusive trials of immunomodulatory treatment strategies.

  Authors: Jochen C Ulzheimer, Sven G Meuth, Stefan Bittner, Christoph Kleinschnitz, Bernd C Kieseier, Heinz Wiendl

  BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. 08/2010; 24(4):249-74.

  Multiple sclerosis (MS) continues to be a therapeutic challenge, and much effort is being made to develop new and more effective immune therapies. Particularly in the past decade, neuroimmunologicMultiple sclerosis (MS) continues to be a therapeutic challenge, and much effort is being made to develop new and more effective immune therapies. Particularly in the past decade, neuroimmunologic research has delivered new and highly effective therapeutic options, as seen in the growing number of immunotherapeutic agents and biologics in development. However, numerous promising clinical trials have failed to show efficacy or have had to be halted prematurely because of unexpected adverse events. Some others have shown results that are of unknown significance with regard to a reliable assessment of true efficacy versus safety. For example, studies of the highly innovative monoclonal antibodies that selectively target immunologic effector molecules have not only revealed the impressive efficacy of such treatments, they have also raised serious concerns about the safety profiles of these antibodies. These results add a new dimension to the estimation of risk-benefit ratios regarding acute or long-term adverse effects. Therapeutic approaches that have previously failed in MS have indicated that there are discrepancies between theoretical expectations and practical outcomes of different compounds. Learning from these defeats helps to optimize future study designs and to reduce the risks to patients. This review summarizes trials on MS treatments since 2001 that failed or were interrupted, attempts to analyze the underlying reasons for failure, and discusses the implications for our current view of MS pathogenesis, clinical practice, and design of future studies. In order to maintain clarity, this review focuses on anti-inflammatory therapies and does not include studies on already approved and effective disease-modifying therapies, albeit used in distinct administration routes or under different paradigms. Neuroprotective and alternative treatment strategies are presented elsewhere.

• Altered expression of ion channel isoforms at the node of Ranvier in P0-deficient myelin mutants.

  Authors: Jochen C Ulzheimer, Elior Peles, S Rock Levinson, Rudolf Martini

  Molecular and cellular neurosciences. 02/2004; 25(1):83-94.

  To elucidate the impact of myelinating Schwann cells on the molecular architecture of the node of Ranvier, we investigated the nodal expression of voltage-gated sodium channel (VGSC) isoforms and theTo elucidate the impact of myelinating Schwann cells on the molecular architecture of the node of Ranvier, we investigated the nodal expression of voltage-gated sodium channel (VGSC) isoforms and the localization of paranodal and juxtaparanodal membrane proteins in a severely affected Schwann cell mutant, the mouse deficient in myelin protein zero (P0). The abnormal myelin formation and compaction was associated with immature nodal cluster types of VGSC. Most strikingly, P0-deficient motor nerves displayed an ectopic nodal expression of the Na(v)1.8 isoform, where it is coexpressed with the ubiquitous Na(v)1.6 channel. Furthermore, Caspr was distributed asymmetrically or was even absent in the mutant nerve fibers. The potassium channel K(v)1.2 and Caspr2 were not confined to juxtaparanodes, but often protruding into the paranodes. Thus, deficiency of P0 leads to dysregulation of nodal VGSC isoforms and to altered localization of paranodal and juxtaparanodal components of the nodal complex.

• Altered expression of ion channel isoforms at the node of Ranvier in P0-deficient myelin mutants

  Authors: Jochen C Ulzheimer, Elior Peles, S.Rock Levinson, Rudolf Martini

  Molecular and Cellular Neuroscience.

  To elucidate the impact of myelinating Schwann cells on the molecular architecture of the node of Ranvier, we investigated the nodal expression of voltage-gated sodium channel (VGSC) isoforms and theTo elucidate the impact of myelinating Schwann cells on the molecular architecture of the node of Ranvier, we investigated the nodal expression of voltage-gated sodium channel (VGSC) isoforms and the localization of paranodal and juxtaparanodal membrane proteins in a severely affected Schwann cell mutant, the mouse deficient in myelin protein zero (P0). The abnormal myelin formation and compaction was associated with immature nodal cluster types of VGSC. Most strikingly, P0-deficient motor nerves displayed an ectopic nodal expression of the Nav1.8 isoform, where it is coexpressed with the ubiquitous Nav1.6 channel. Furthermore, Caspr was distributed asymmetrically or was even absent in the mutant nerve fibers. The potassium channel Kv1.2 and Caspr2 were not confined to juxtaparanodes, but often protruding into the paranodes. Thus, deficiency of P0 leads to dysregulation of nodal VGSC isoforms and to altered localization of paranodal and juxtaparanodal components of the nodal complex.