Neurological disorders, applications

Purpose The mission of the National Institute of Neurological Disorders and Stroke (NINDS) Office of Translational Research is to facilitate the pre-clinical discovery and development of new therapeutic interventions for neurological disorders. The Office supports pre-clinical projects from the discovery of candidate therapeutics through IND and Investigational Device Exemption (IDE) applications to the FDA. This is accomplished through both access to NINDS contract resources and direct funding mechanisms. 

Complexity of inhibition of PLP-dependent enzymes is highlighted by detailed investigations on the inhibition of y-aminobutyric acid aminotransferase (GABA-AT), the enzyme responsible for the degradation of y-aminobutyric acid (GABA), one of the major inhibitory neurotransmitters in the mammalian central nervous system. Inhibition of GAB A-AT results in an increased concentration of GABA in the brain and could have therapeutic applications in neurological disorders (epilepsy, Parkinson disease, and Alzheimer disease). 

Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M (1986) MR imaging of intravoxel incoherent motions application to diffusion and perfusion in neurologic disorders. Radiology 161 401-407... 

Eountouiakis, M. (2001). Proteomics current technologies and applications in neurological disorders and toxicology. 

Miller TW, Messer A (2005) Fitiabody applications in neurological disorders Progress and future prospects. Mol Ther 12 394- 01. 

Berman (B4) reported the clinical application of atomic absorption spectroscopy in the determination of copper in blood, urine, and tissues. After acid digestion of the samples, copper was complexed with EDTA and diethylthiocarbamate and extracted into a ketone. Copper levels in blood and urine from normal persons were compared to those found in patients with neurological disorders. 

Benoit )P, Eaisant N, Venier-)ulienne MC, Menei P Development of microspheres for neurological disorders from basics to clinical applications, J Control Release 2000, 65, 285-296. 

Aristolochic acid I (5) was also reported to exhibit antibacterial action against Staphylococcus aureus, Diphococcus pneumoniae and Streptococcus pyogenes in infected mice at 50 pg/kg ip [415]. When, rats with wounds infected with S. aureus were treated intraperitoneally or orally with aristolochic acid I (5), they recovered much faster than control. In mice with Pneumococci infections were influenced very well by aristolochic acid I (5). Rabits after intravenous application of aristolochic acid I (5) showed an increased antibacterial action of serum. Aristolactam la (64) and aristolochic acid I (5) showed antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, S. faecalis, S. aureus and S. epidermides [191]. Neurological disorders, especially Parkinson s diseases have been treated by the administration of the aristolactam taliscanine (91) to the affected patient [439]. Cepharadione A (107) exhibited antimicrobial activities [440],... 

Numerous applications are now encountered where FA chromatographic profiles of a human physiological fluid or tissue are correlated to certain pathological conditions. A few representative examples will now be mentioned that include both free (non-esterified) FA and the saponified lipids. The identification of a methyl-branched FA (phytanic acid) in plasma of the patients with Refsum s disease [360] is now a widely known example of the power of GC in studying various metabolic defects. The profiles of FA from brain ti.ssue lipids were investigated for various neurological disorders [361,362] and in experimental animals [363]. Tichy et al. [364] determined FA in different lipids isolated from the cerebrospinal fluid while the FA profiles in cerebrospinal fluid differ from those in blood serum, no obvious correlations between the FA composition and human neurological complications were established at this time. 

Although stem/progenitor cell and hUCB biotechnologists have realized commercial potentials of human stem cell research, clinical applications of human cell for the treatment of neurological disorders have been the subject of intense ethical and legislative considerations. Very little is known about neurochemical aspects... 

Additionally, there are many emerging indications for wearable or implantable medical devices, particularly new neuromodulation applications such as deep brain stimulation for various movement and neurological disorders [57] and occipital nerve stimulation to treat migraine and cluster headaches [58]. Implantable visual prostheses to restore sight are also under development. 

---