SF-12 physical component summary score (baseline, 34.20; third infusion, 36.05; sixth infusion, 36.34) and the SF-12 mental component summary score (baseline, 43.25; third infusion, 47.35; sixth infusion, 47.92) showed statistically significant improvements over time.
[Editor’s note: For more information on natalizumab, please see a related news story and commentary on page 5.]
Genetic Targets for Potential MS Therapies
Two genes in mice were associated with good CNS repair in multiple sclerosis (MS). The findings may help researchers develop more effective therapies and predict outcomes for patients with MS.
“Most MS genetic studies have looked at disease susceptibility—or why some people get MS and others do not,” said Allan Bieber, PhD, Assistant Professor of Neurology at the Mayo Clinic in Rochester, Minnesota. “This study asked, among those who have MS, why some do well with the disease while others do poorly, and what might be the genetic determinants of this difference in outcome.”
Dr. Bieber and a team of Mayo Clinic researchers used two different strains of mice with a chronic, progressive MS-like disease. One strain of mice progressed to paralysis and death. The other strain underwent the initial damage induction phase of the disease and then had spontaneous repair of the damage to the CNS and retained most neurologic function. Using the genetic mapping techniques that are available for mice, the team mapped two strong genetic determinants of good disease outcome.
“It’s possible that the identification of these genes may provide the first important clue as to why some patients with MS do well, while others do not,” said Dr. Bieber. “The genetic data indicate that good CNS repair results from stimulation of one genetic pathway and inhibition of another genetic pathway. While we’re still in the early stages of this research, it could eventually lead to the development of useful therapies that stimulate or inhibit these genetic pathways in patients with MS.”
According to Dr. Bieber, the research suggests that there may be a small number of strong genetic determinants for CNS repair following demyelinating disease, rather than a larger number of weak determinants.
“If that’s true, it may be possible to map the most important genetic determinants of CNS repair in patients with MS and define a reparative genotype that could predict patients’ outcomes,” said Moses Rodriguez, MD, Professor of Neurology and Director of the Mayo Clinic’s Center for Multiple Sclerosis and Central Nervous System Demyelinating Diseases Research and Therapeutics. “Such a diagnostic tool would be a great benefit to patients with MS and is consistent with the concepts of individualized medicine.”
Research Supports the Importance of Early Treatment in Patients With MS
Findings from two observational studies—CogniCIS and CogniMS—revealed that depression and fatigue occur alongside cognitive deficits, even early in the disease. Data from these studies showed that relatives were able to detect even minor changes in cognitive performance at an early stage of the disease, which the patients themselves did not report.
“Cognitive impairment in patients with multiple sclerosis (MS) is not sufficiently recognized, in spite of the significant negative impact it can have on patients’ lives,” said Dawn Langdon, PhD, Neuropsychology Lead and Reader in Neuropsychology, Royal Holloway, University of London, UK, and lead investigator of CogniCIS and CogniMS. “These studies will help us construct a more complete picture of the development and impact of cognitive decline in early MS. Such findings, added to the existing evidence, will have important implications for physicians when making management decisions.”
The CogniCIS study collected cognitive and psychosocial data from 394 patients with clinically isolated syndrome (CIS). A subset of 130 European patients with CIS and 60 of their relatives completed the MS Neuropsychological Questionnaire (MSNQ), which asks about cognitive difficulties. Preliminary results presented showed that scores on the MSNQ from patients with CIS and their relatives correlated more with the patients’ level of depression, fatigue, and quality of life rather than performance in cognitive tests.
The CogniMS study included psychosocial data from 1,509 patients with early MS. A subset of 274 patients and 178 of their relatives completed the MSNQ. According to preliminary findings from the trial, relatives’ reports of the patients’ cognition correlated with some cognitive test scores, obtained by patients; patient self-reported cognitive deficits were not closely related to objective test scores. Similar to results from CogniCIS, the CogniMS findings suggest that self-reported cognitive deficits in an early MS population are not specific to cognition, and are influenced by the patients’ psychologic situation.