Gene Therapy Promising in Muscular Dystrophy
NEW YORK, May 4 (Reuters Health) — The results of a phase I/II study of patients with limb-girdle muscular dystrophy (LGMD2D), which is associated with a faulty α-sarcoglycan gene (SGCA), indicated that gene replacement therapy may be successful, researchers reported in the April 16 online issue of the Annals of Neurology.
As lead investigator Dr. Jerry R. Mendell told Reuters Health, “The successful delivery and sustained expression of the α-sarcoglycan gene in the muscle of LGMD2D patients positions our team and others to achieve more meaningful results in the fight against this disease.”
Dr. Mendell of the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, and colleagues studied three teenage LGMD2D patients who were given injections of the SGCA gene into the extensor digitorum brevis muscle. The corresponding muscle in the other foot was the target of control saline injections.
After six weeks, compared with the control side, there was a four- to fivefold increase in SGCA gene expression in two patients. At three months, the third patient also had an increase in SGCA expression.
The full sarcoglycan complex was restored in all three patients, and the muscle fiber size was increased in the patient who showed a response at three months.
“Our ultimate goal,” continued Dr. Mendell, “is to reach multiple muscles, an approach that could help overcome the disability by strengthening an entire limb.
“The findings in this first successful trial,” he concluded, “lay the foundation for this type of approach.”
Ann Neurol. 2009 Apr 16; [Epub ahead of print].
CRP Levels at Admission Tied to Stroke Outcome
NEW YORK, May 15 (Reuters Health) — Levels of the inflammatory marker C-reactive protein (CRP) measured within 24 hours of stroke onset are associated with the severity of the event and long-term mortality, Norwegian researchers reported in the April 28 BMC Neurology.
“Our study shows that high CRP predicts severe stroke and (greater mortality) in patients with stroke,” lead investigator Dr. Titto T. Idicula told Reuters Health.
Dr. Idicula and colleagues at Haukeland Hospital, Bergen, Norway, prospectively studied 498 patients who were admitted to the institution within 24 hours of ischemic stroke onset.
The median CRP at admission was 3 mg/L, and a CRP of 10 mg/L reflected the upper 20% distribution.
Seventy-nine percent of those deemed to have a low CRP had mild stroke. Only 60% of the high-CRP group had mild stroke.
After adjustment, high CRP continued to be associated with high NIH Stroke Scale scores and with high long-term mortality.
Although mortality was measured over a period of two and a half years, the researchers pointed out that “since we did not have data on the causes of death, we cannot be certain that the high mortality in patients with elevated CRP is due to vascular events.”
The team concluded that CRP is an independent predictor of long-term mortality after ischemic stroke and is associated with stroke severity.
“The findings are interesting,” added Dr. Idicula, “because new medicines to treat high CRP are in the pipeline, though the risks and the benefits of such medications are yet to be proven.”
BMC Neurol. 2009 Apr 28;9:18.
Prior Stroke Associated With Particular Pattern of Cognitive Impairment
NEW YORK, May 19 (Reuters Health) — Older adults with a history of stroke, but without a diagnosis of dementia, have an increased risk of nonamnestic mild cognitive impairment and impairment of nonmemory cognition, according to findings published in the May issue of the Archives of Neurology. Those with the apolipoprotein (APOE) ε4 genotype were also more likely to have memory impairment and amnestic mild cognitive impairment.
“The relationship between stroke and cognitive impairment has been enigmatic,” Dr. David S. Knopman, of Mayo Clinic College of Medicine, Rochester, Minnesota, and colleagues wrote. “The link between large strokes that lead to immediate and persistent neurologic impairment has never been questioned,” they noted. “However, the role of single strokes that may not produce immediate cognitive impairment is less well understood.”
In the current study, the researchers examined associations between stroke history, APOE genotype, and subtypes of mild cognitive impairment. Residents of Olmsted County, Minnesota, between the ages of 70 and 89 were randomly selected on October 1, 2004, and subjects without dementia were invited to participate in the study.
Participants were evaluated through interviews, a neurologic evaluation, and neuropsychologic testing. Neuropsychologic testing included tests to assess memory, attention, executive function, visuospatial cognition, and language. The subjects were diagnosed as cognitively normal; with mild cognitive impairment (amnestic or nonamnestic); or with dementia. Stroke history was obtained by self-reports and confirmed in the subjects’ medical records.