NEUROBIOTECHNOLOGY 2005
This theme issue explores new and emerging biotechnologies that will enhance our knowledge of neurological disease. The first 7 article titles noted below relate to this theme.
Mouse Models of Human Neurodegenerative Disorders
Bloom and colleagues (SEE ARTICLE) emphasize that transgenic mouse models offer opportunities to detect and follow pathologic progression and provide potential biomarkers by which to assess therapeutic interventions for human neurodegenerative disease. Evidence for Alzheimer disease suggests some starting requirements for the experimental data that could enhance the likelihood of developing medications in these mouse models that would be effective in humans.
Defining Molecular Targets to Prevent Alzheimer Disease
Selkoe (SEE ARTICLE) predicts that middle-aged adults will commonly undergo a formal risk assessment for Alzheimer disease that will include measurements of plasma
-amyloid and perhaps cerebrospinal fluid
-amyloid and tau levels, and quantitative assessment of brain
-amyloid burden by imaging procedures. Based on the results, patients would be offered 1 of several potentially disease-slowing therapies. The future approach to Alzheimer disease is identification of disease in its earliest state and initiation of specific therapy to prevent progression of its clinical expression.
Imaging Technology for Neurodegenerative Diseases
Mathis and colleagues (SEE ARTICLE) describe advances in neuroimaging over the past 2 decades. Recent advances in imaging
-amyloid plaques offer a great technological breakthrough and present the possibility for more efficient assessment of anti-amyloid interventions as well as specific noninvasive diagnostic capabilities.
Laser Capture Microdissection in the Study of Neurodegenerative Disease
Standaert (SEE ARTICLE) points out that laser capture microdissection is a new technology that is becoming increasingly important for studies of neurodegenerative disease. In the near future, this powerful new tool will provide important insights into the etiology of neurodegenerative diseases and the basis of selective vulnerability.
Blood Gene Expression Profiling of Neurologic Diseases
Tang and colleagues (SEE ARTICLE) present data concerning the association of neurological diseases with unique patterns of up- and down-regulated genes in whole blood. Patients with neurofibromatosis, epilepsy, and Tourette syndrome were studied for their blood gene expression levels of greater than 12 000 genes measured with Affymetrix U95A arrays. They find that in general blood gene expression profiling can provide surrogate markers for neurological diseases.
Fate of Human Neuronal Progenitor Cells Transplanted in Rat Spinal Cord
Li and colleagues (SEE ARTICLE) have transplanted immortalized human neuronal progenitor cells into the rat spinal cord. They were rejected after 4 weeks, despite cyclosporine immunosuppression. Their results suggest that the xenotransplantation failed because of apoptotic cell death, possibly involving natural killer cells. The techniques and methods developed in this research program will be vital to subsequent work on attempts to transplant cells into injured human spinal cord.
Genomics of Oxidative Stress in Glioma
Fathallah-Shaykh (SEE ARTICLE) utilizes specific genome-scale expression discovery to identify genes differentially expressed in cultured glioma cells vs normal brain tissue. The discovered states of expression show a cohesive molecular system that protects rapidly growing glioma cells from endoplasmic reticulum and oxidative stressinduced apoptosis.
Rasagiline in Levodopa-Treated Parkinson Disease: The PRESTO Study
The Parkinson Study Group (SEE ARTICLE) has studied the safety, tolerability, and efficacy of rasagiline, a selective monoamine oxidase type B inhibitor, in levodopa-treated patients with Parkinson disease (PD) with motor fluctuations. Rasagiline improves motor fluctuations and PD symptoms in levodopa-treated patients with PD. It is a promising new treatment for PD.
Intravenous Methylprednisolone in Treating Polyneuropathy
Lopate and colleagues (SEE ARTICLE) have studied the efficacy and safety of high-dose, intermittent intravenous methylprednisolone as initial and chronic maintenance therapy for patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). They report that treatment of patients with CIDP using intermittent intravenous methylprednisolone results in improved strength equal to that found with the use of intravenous immunoglobulin and oral prednisone.
Rituximab on B Cells in Patients With Primary Progressive Multiple Sclerosis
Monson and colleagues (SEE ARTICLE) show that rituximab, an anti-CD20 monoclonal antibody that depletes CD20+ B cells, in patients with primary progressive multiple sclerosis temporarily suppressed the activation state of B cells in cerebrospinal fluid. The effects are limited in comparison with the effects in the periphery and will need to be confirmed in a larger group of patients.
High Prevalence of Ulnar Neuropathy in Patients Receiving Hemodialysis
Nardin and colleagues (SEE ARTICLE) show there is a high prevalence of ulnar neuropathy in patients with end-stage renal disease receiving hemodialysis. Ulnar neuropathy was documented in 51% of 73 patients, and preventive measures are indicated.
Fatigue and the Hypothalamo-Pituitary-Adrenal Axis in Multiple Sclerosis
Gottschalk and colleagues (SEE ARTICLE) describe a high level of activity of the hypothalamo-pituitary-adrenal axis in patients with multiple sclerosis with fatigue compared with those without fatigue.
Structural Changes in Parkinson Disease With Dementia
Summerfield and colleagues (SEE ARTICLE) studied magnetic resonance images in patients with Parkinson disease with and without dementia and also in healthy age-matched controls using voxel-based morphometry analyses of gray matter. The hippocampus, thalamus, and anterior cingulate were the regions most affected in dementia in Parkinson disease.
Active Head-Impulse Test in Vestibulopathy
Black and colleagues (SEE ARTICLE) show that passive head-impulses are necessary to detect a severe unilateral peripheral vestibulopathy and that active head-impulses will produce a false-negative result.
Functional Correlates and Prevalence of Mild Parkinsonian Signs in a Community Population of Older People
Louis and colleagues (SEE ARTICLE) show that mild parkinsonian signs, and particularly axial dysfunction, were associated with functional disability in a community population.