Corinne Goldsmith Dickinson Center for Multiple Sclerosis

History

The Center was established in 2001 with a $5 million endowment from George J. Gillespie, III and Mount Sinai Hospital trustee Clifford H. Goldsmith. It is named in honor of Goldsmith's daughter, Corinne, who coped with the disease until her death in 1999.

Basic research

The pathologic hallmarks of multiple sclerosis are central inflammation, blood–brain barrier permeability, demyelination, progressive axonal transection, and a reactive astrogliosis. Demyelination is associated with conduction deficits in affected nerves, including conduction block, a major cause of symptoms early in the disease, and has also been linked to axonal loss, which is associated with permanent deficits later in the disease course. Conversely, remyelination is associated with return of conduction and clinical recovery, but remyelination often fails as the disease progresses, for reasons that are not well understood.

Research in the CGD Center's laboratory (led by Dr. Gareth John) focuses on the mechanisms that control lesion formation and repair in MS. The laboratory is currently supported by grants from the National Institutes of Health, the National Multiple Sclerosis Society, biotech corporations, and private benefactors; work from the laboratory has been published in scientific journals including Nature Medicine and the Journal of Neuroscience.

In a recent study, team members identified the soluble mediator interleukin-11 (IL-11) as a factor that potentiates the survival and maturation of oligodendrocytes, the cells in the brain that produce myelin and are the target of immune attack in MS. Interestingly, IL-11 expression is upregulated at the border of remyelinating lesions in MS, and it may represent a potential target for the design of new therapies to promote lesion repair. These findings were recently published (Zhang et al., J. Neurosci. 2006; 26:12174-85 PMID 17122042).

Using a related approach, members of the laboratory recently found that signaling through Notch1 receptors is activated in oligodendrocyte progenitor cells (OPC) in MS lesions. In the developing CNS, Notch1 restricts OPC differentiation, and is permissive for progenitor expansion. Thus, activation of this pathway in the adult may regulate remyelination. To test this hypothesis, the laboratory has targeted Notch1 inactivation to early OPC in genetically modified animals, using OLIG1Cre:Notch1^12f/12f mice. They have found that remyelination is potentiated in these animals, whereas OPC proliferation is restricted. These results suggest regulation of Notch signaling as a therapeutic avenue to enhance remyelination in MS. They were recently submitted for publication.

These studies and others from the laboratory have produced findings that may be relevant to lesion repair in MS. They share a common molecular/cellular approach, beginning with target identification using functional genomics, and progressing through experiments in tissue culture models and into genetically modified animals. The long-term goal of this research is to identify novel therapeutic strategies for MS.

With new drug therapies emerging rapidly, the CGD Center has established a clinical trials program to design and implement tests of experimental agents and allow patients access to therapies not yet widely available.

Clinical care

The CGD Center sees over 4,800 patients annually, 1,000 of whom each year are new. The Center utilizes a team of doctors, nurse practitioners, fellows, social workers, consultants and a psychiatrist in its integrated approach to enhancing the treatment of MS, attracting visiting neurologists and patients worldwide.

Community and patient support

Many MS Centers provide additional resources with the understanding that some of the most immediate concerns of the newly diagnosed are not medical but social and psychological. In addition to providing full-time social workers for patients and their families through two LCSWs, the CGD Center is unique in providing the services of a psychiatrist trained in the psychiatric manifestations of MS. The Center also provides monthly patient education seminars discussing research and treatment topics.