Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Phase I, double-blind, placebo-controlled, single-dose, escalation study of the purine derivative, AIT-082 (Neotrofin, NeoTherapeutics, Inc.) was conducted in healthy elderly volunteers. This trial was designed to evaluate single-dose safety, tolerability, and pharmacokinetics. Potential cognitive domains that might benefit from AIT-082 were preliminarily investigated. AIT-082 is currently being developed as a potential treatment for Alzheimer's disease (AD). Preclinical studies indicate that AIT-082 has memory-enhancing properties, stimulates neuritogenesis, and upregulates neurotrophic factors. Subjects received a single oral dose of AIT-082 or placebo on a weekly basis for 5 wk. All patients received a placebo dose at baseline. Six subjects received increasing doses of AIT-082 over the next 4 wk at doses of 0.6, 2.0, 6.0, and 20.0 mg of AIT-082 per kilogram of body weight. Two subjects received placebo throughout the trial. Nine subjects were recruited. One subject was withdrawn after the third treatment visit owing to poor venous access. There were no serious adverse events. The drug was well-tolerated. The time to peak drug concentration was approx 85 min with an elimination half-life of approx 17.6 h. Performance on the Number Comparison, Symbol Digit, and Trails A tests improved with AIT-082 dosing compared to baseline (placebo). In conclusion, AIT-082 was rapidly absorbed by the oral route with a half-life suitable for once daily dosing. No problems with tolerability or safety were demonstrated.
J Mol Neurosci 2002 Jun
PMID:A phase I study of AIT-082 in healthy elderly volunteers. 1205 47

We report peripheral actions in rats of Neotrofin, a purine derivative of therapeutic interest. Systemic injections mimicked NGF in eliciting sprouting of nociceptive nerves without affecting their regeneration. The sprouting was prevented by anti-NGF treatment, implicating endogenous NGF. We detected no Neotrofin-induced increases in cutaneous NGF levels or in retrograde NGF transport. In contrast, both NGF and phosphorylation of trkA increased significantly in DRGs, with a marginal appearance of phosphorylated trkA in axons. We conclude that the DRG effects of Neotrofin are responsible for its induction of sprouting. Neotrofin also induced a striking phosphorylation of axonal erk 1 and 2, which was, however, unaffected by anti-NGF treatment. We suggest that this NGF-independent MAP kinase activation is involved in nonsprouting functions of Neotrofin such as neuroprotection. Unlike injected NGF, Neotrofin did not induce hyperalgesia, supporting its candidacy as a treatment for peripheral neuropathies like those induced by diabetes and anticancer chemotherapy.
Mol Cell Neurosci 2003 Nov
PMID:Neotrofin, a novel purine that induces NGF-dependent nociceptive nerve sprouting but not hyperalgesia in adult rat skin. 1466 8