10 RESEARCH & DEVELOPMENT

Gene therapy shows promise in rat model of Parkinson's disease

Researchers from Japan and the pharmaceutical company Avigen have demonstrated, through the use of a rat model, the potential of gene therapy in Parkinson's disease. The results of their study were presented at the 27th Annual Meeting of the Society for Neuroscience.

In the study, an adeno-associated virus vector was introduced into the brains of rats with laboratory­induced Parkinson's disease. The vector delivered genes encoding 2 enzymes involved in the production of dopamine, tyrosine hydroxylase and L-amino acid decarboxylase.

A significant reduction in abnormal rotational movement was seen in the rats that received either I or both genes. The response in the rats that received 2 genes was greater than that of the rats that received only I gene.

'Parkinson s disease is a particularly attractive target for gene therapy because . .. the particular defect underlying the disease and area of the brain affected is well understood', commented Dr John Monahan, the president of Avigen. Avigcn Inc. Avigcn demonstrates gene therapy success in treating animal model ofParlrinson's disease. Media Release: [2 pages]. 27 Oct 1997 1IIlOW"9

VA-I0,367 shows promise in rat models of nerve injury

The neurophilin compound VA-1O,367* accelerates functional recovery and nerve regeneration in rat models of both spinal cord injury and peripheral nerve injury, according to the results of studies presented at the 27th Annual Meeting of the Society of Neuroscience.

In the rat model of spinal cord injury, 2 days of oral therapy with VA-1O,367 enhanced the functional recovery of the animals.

Similarly, in another rat model involving injury of the sciatic nerve, rats that received VA-1O,367 had accelerated onset of foot movement and walking, compared with controls. In addition, VA-IO,367 therapy was shown to enhance the regeneration of the injured nerves. * lena Vemx Pharmaceuticals Incorporated. Vemx Neurophilin compound acceleraleS

nerve regcneraton in rodent models of centta1 and peripbcral nerve injury. Media Release: [2 pages J. 28 Oct 1997 IIIlOW 117

Inpharma- • Nov 11187 No. 1112

Licostinel: lower doses may be effective

The clinically effective dose of the NMDA receptor antagonist licostinel* [ACEA-I02I] may be lower than previously thought, according to the results of preclinical studies presented at a satellite symposium of the 27th Annual Meeting of the Society for Neuroscience.

In previous phase I trials, licostinel crystals were detected in the urine of individuals who received the highest dosages of the drug.

However, additional preclinical trials in animal models of stroke have demonstrated that the minimum dose required for neuroprotective efficacy may be 3 to 4 times lower than doses that were well tolerated in previous clinical studies.

Dr Eckard Weber, senior vice president of Research and Drug Discovery at CoCensys commented that the results of the animal studies 'are encouraging because they suggest that we may reach neuro­protective levels with licostinel at doses that were well-tolerated in our earlier clinical safety studies'.

The results of another animal study indicate that concomitant administration of licostinel and probenecid reduces the elimination of licostinel via the kidneys by up to SO%, and leads to increased blood levels of licostinel. * CoCensys; phase II in strok£ CoCensys presents new data on lead stroke drug at neuroscience symposium. PR Newswire [online): [3 pagesl. 28 Oct 1997. Available from: URL: bttp:/lpnpl.individual.com 1I0062:I,..

News in brief ...

• AIT-082* increased levels of neurotrophic factors in a rat model of spinal cord injury, according to the results of a study presented at the 27th Annual Meeting of the Society of Neuroscience. In the study, rats with spinal cord injuries received treatment with the synthetic purine analogue AIT-OS2. After 7 days' therapy, the levels of ciliary neurotrophic factor and brain-derived neurotrophic factor had increased. * NeoTnerapeUlics; phase /I inAkJleimo's disease Nco1benJpeutics Inc. New research findings for spinal cord injury are presented;

report at the Society of Neuroscience 27th Annual Meeting. Media Release:

[1 page]. 28 Oct 1997

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