American Academy of Neurology Review 4/28 & 4/29

Tuesday, April 29th

Today’s Tisch MS Center poster presentations included:

Transient Neurologic Worsening after Initiation of Dimethyl Fumarate Therapy in Progressive Multiple Sclerosis Patients

James W Stark, Sydney Chirls, Saud Sadiq

Summary: We identified 18 patients with progressive forms of MS who experienced worsening of neurologic symptoms soon after starting the new medication called Tecfidera. All patients recovered to baseline status upon cessation of the medication. The mechanism of this worsening is not understood, but appears similar to the well-known phenomena of pseudo-relapse. 

Safety and Dosing of Autologous Neural Progenitors Injected Intrathecally in Multiple Sclerosis Patients: Results of a Pilot Study

Saud A Sadiq, Sydney Chirls, Daniel Koffler, Violaine K Harris

Summary: Six patients with progressive forms of MS and one with spinal cord atrophy were given between 2 and 5 injections via spinal tap of their own mesenchymal stem cell-derived neural progenitors (MSC-NPs) spaced an average of 5 months apart as part of an exploratory pilot study. There were no significant short-term or long-term adverse events, and 4 out of 6 MS patients showed a measureable clinical improvement as a result of the MSC-NP treatments. Based on these initial findings, it was determined that MSC-NPs administered by intrathecal injection every 3 months would be safe and feasible.

FDA-Approved Phase I Clinical Trial of Autologous Neural Progenitors Injected Intrathecally in Multiple Sclerosis

Violaine K. Harris, Daniel Koffler, Sydney Chirls, and Saud A. Sadiq

Summary: This study is a 20 patient, open-label, phase I clinical study of autologous mesenchymal stem cell-derived neural progenitors (MSC-NPs)administered via spinal tap in three injections spaced three months apart. The primary goal of the study is to evaluate the safety of the treatments, while the secondary goal is to observe trends in efficacy include neurological exam, MRI, evoked potentials, and urodynamic testing. The 1st study subject was treated one month ago and no adverse events have been reported. 

Monday, April 28th

The Tisch MS Research Center presented several posters today at the annual AAN meeting in Philadelphia. These include:

Inhibition of Hyaluronan Synthesis Protects Against EAE by Inducing CXCL12 in the CNS

Andre M. Mueller, Bo Hyung Yoon, Saud A. Sadiq

Summary: Inhibition of a molecule called hyaluronan synthesis is protective in a mouse model of MS by interfering with T-cells and reducing the movement of immune cells into the brain. 

Development of Inflammatory Demyelinating Lesions In Mouse CNS After Injection Of Cerebrospinal Fluid Derived From Progressive MS Patients

Massimiliano Cristofanilli, Daniel Gratch, Benjamin Pagano, Saud Sadiq

Summary: The factors responsible for the loss of myelin and neurodegeneration, characteristic of progressive forms of MS, are present in patients' cerebrospinal fluid and are capable of inducing MS-like pathology in mice. These findings present an opportunity to explore and establish a new mouse model specifically for progressive MS. 

Adult Neural Progenitor Cells Derived From MS Patients Differentiate Into MBP Expressing Cells In The Shiverer Mouse

Massimiliano Cristofanilli, Benjamin Pagano, Daniel Gratch, Violaine Harris, Tamara Vyshkina, Saud Sadiq

Summary: Neural progenitor cells derived from MS patients (MSC-NPs) differentiate into myelin forming cells after injection into the brains of newborn and adult mice genetically engineered to lack myelin. The findings suggest that in the proper CNS milieu, MSC-NPs may promote remyelination and neural repair.