New Findings on MS Therapies
esearchers at New Jersey Medical School have found that one FDA-approved multiple sclerosis medication, Betaseron (interferon beta-1b), is more effective than another medication, Copaxone (glatiramer acetate), in limiting the formation of so-called “chronic black holes” in the brain that are believed to represent irreversible damage in multiple sclerosis. Their findings have been published online by the Journal of Neurology, Neurosurgery & Psychiatry.
This study is the latest analysis of data to emerge from the ongoing BECOME trial (Betaseron vs Copaxone in MS with Triple-Dose Gadolinium and 3-T MRI Endpoints), conducted by UMDNJ, which for two years closely followed 75 patients in northern NJ with either relapsing-remitting MS or a clinically isolated syndrome (CIS), often the initial clinical manifestation of MS.
“This is the first and largest head-to-head trial by sensitive monthly MRI technology comparing two leading medications, and it has produced a wealth of information about the natural history of multiple sclerosis during treatment with first line MS therapies,” says Stuart D. Cook, MD, a professor of neurology and neurosciences at NJMS and an author of the study. “Important findings to date include longer duration of enhancing lesions than earlier thought, the higher rate of enhancing lesions before T2 lesions occur, and the ratio of asymptomatic new MRI lesions to clinical symptoms (30 to 1).”
An earlier paper emerging from the BECOME trial, published in June in the journal Neurology (Neurology. 2009; 72: 1976-1983), showed similar outcomes for the two tested medications, where the criteria were the appearance of new active or enhancing MS lesions in the brain and of new clinical exacerbations in patients.
This latest study, however, indicates a divergence between the two medications with regard to the evolution of chronic black holes from newly enhancing lesions. Among newly enhancing MS lesions in patients receiving Betaseron, 9.8 percent converted to chronic black holes (black holes with duration beyond a year), while 15.2 percent of new lesions in patients receiving Copaxone converted (P=0.02). In addition, the rate of conversion from acute black holes to chronic black holes was lower in patients receiving Betaseron (15.2 percent) than in patients receiving Copaxone (21.4 percent), though that difference was only of borderline statistical significance (P=0.06).
To the extent that chronic black holes are linked in the future to long-term
progression and disability in MS, Cook says these findings, if confirmed, could influence treatment of patients with the disease. .
— by Rob Forman
Can Alzheimer’s Brain Damage Be Repaired?
A diagnosis of Alzheimer’s often comes after a patient’s brain cells have battled to repair damage caused by the relentless progression of the disease for nearly a decade.
Research published by scientists from the School of Osteopathic Medicine (SOM) provides evidence of this battle and suggests a promising path for novel therapeutic agents. Writing in Brain Research, the investigators identified a protein, vimentin, that normally appears twice in a human being’s lifetime — when neurons in the brain are forming during the first years of life and years later when the brain’s neurons are under siege from Alzheimer’s or other neurodegenerative diseases.
“Vimentin is expressed by neurons in regions of the brain where there is Alzheimer’s damage but not in undamaged areas of the brain,” explains Robert Nagele, PhD, a professor at SOM and the study’s corresponding author. “When the patient shows up at the doctor’s office with symptoms of cognitive impairment, the neurons have reached the point where they can no longer keep pace with the ever-increasing damage caused by Alzheimer’s.”
In explaining the findings, Nagele likened neurons to a tree with long strands called dendrites branching off from the main part of the cell. The dendrite branches are covered with 10,000 tiny “leaves” called synapses that allow neurons to communicate with each other. Vimentin is an essential protein for building the dendrite branches that support the synapses.
“A hallmark of Alzheimer’s is the accumulation of amyloid deposits that gradually destroy the synapses and cause the collapse of dendrite branches,” he states. “When the dendrites and synapses degenerate, the neuron releases vimentin in an attempt to re-grow the dendrite tree branches and synapses. It’s a rerun of the embryonic program that allowed the brain to develop in the early years of life.”
The researchers reported some initial findings that indicate a similar damage response mechanism takes place following traumatic brain injury, suggesting the possibility that similar therapeutic agents could be developed to enhance repair both for sudden brain trauma and for progressive neurodegenerative diseases.
The research was supported by the Alzheimer’s Association, the New Jersey Governor’s Council on Autism, the New Jersey Commission on Science and Technology and the Foundation of UMDNJ. The study’s authors included researchers from UMDNJ, Johnson and Johnson Pharmaceutical Research and Development, and the Department of Physiology and Pharmacology at The City University of New York Medical School. .
— by Jerry Carey
Impact of Massage on Osteoarthritis
A federal grant of $1.4 million will underwrite a two-year study to determine the optimal dosing regimen of massage that benefits patients with osteoarthritis of the knee. Adam Perlman, MD, MPH, executive director of the Institute for Complementary & Alternative Medicine (ICAM) at UMDNJ’s School of Health Related Professions (SHRP), is the study's principal investigator. In 2004, he led a pilot study of 68 patients with this condition, demonstrating that a course of Swedish massage is safe, and decreases pain and increases function. Results were published in Archives of Internal Medicine in December 2006.
“Safe and effective adjunct treatments for osteoarthritis are extremely important in light of the pain and disability caused by this condition, its prevalence and the high rates of undesirable side effects associated with current drug treatments,” says Perlman, who is the UMDNJ Endowed Professor of Complementary and Alternative Medicine and chair of the Department of Primary Care at SHRP. The condition affects 21 million Americans.
According to Perlman, 125 participants will be enrolled in this study. Subjects will be randomly assigned to one of five groups, a usual care group or one of four different massage groups. Among the massage groups, treatments will vary by length (one hour versus 30 minutes) and frequency (once a week versus twice a week) over a two-month period. The goal is to identify the optimal therapy course for reducing pain and improving function for patients with a diagnosis of osteoarthritis of the knee.
UMDNJ is now recruiting participants for the Livingston site, where more than half the participants will be enrolled. Like the pilot, the current study is a collaboration involving UMDNJ, the Saint Barnabas Ambulatory Care Center in Livingston and the Yale Griffin Prevention Research Center. It is funded with an R01 research grant through the National Center for Complementary and Alternative Medicine, part of the NIH. The grant money is provided through the American Recovery and Reinvestment Act (ARRA). Research will be conducted at Yale and at the Siegler Center for Integrative Medicine, part of the Saint Barnabas Ambulatory Care Center. Perlman is the founding medical director of the Siegler Center.