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Amgen neuroscience research targets nervous system disorders

HOUSTON. Amgen, the largest biotechnology company in the world, is funding research focusing on disorders that destroy parts of the nervous system. These include Alzheimer's disease, Parkinson's disease, multiple sclerosis and stroke. Medicines for disorders resulting from dysfunction of the neuroendocrine system such as obesity and Type 2 diabetes are also under development. In both areas, Amgen licenses product candidates and technologies that complement its internal drug discovery and develop

By | November 6, 2000

HOUSTON. Amgen, the largest biotechnology company in the world, is funding research focusing on disorders that destroy parts of the nervous system. These include Alzheimer's disease, Parkinson's disease, multiple sclerosis and stroke. Medicines for disorders resulting from dysfunction of the neuroendocrine system such as obesity and Type 2 diabetes are also under development. In both areas, Amgen licenses product candidates and technologies that complement its internal drug discovery and development programmes.

Advances in cellular and molecular biology are leading to the discovery and production of neurotrophic factors. These naturally occurring proteins protect and promote the growth of specific nerve cells. Neurotrophic factors bind to specific neuronal receptors thereby stimulating biochemical events in the cell that maintain or improve nerve cell function. Because of these properties, neurotrophic factors hold promise as treatments to halt and possibly even reverse nerve damage caused by neurodegenerative diseases.

Genomics research is providing growing support to Amgen's neuroscience R&D efforts by identifying genes that encode proteins, which are not themselves therapeutically useful but may serve as targets for the development of small molecule drugs. Two examples are: the AGRP gene, which encodes a protein involved in the leptin signalling pathway; and a component of telomerase, thought to be important in cancer and ageing. In January 1999, Amgen and Celera Genomics Corporation signed a five-year agreement giving Amgen access to three Celera drug discovery and development databases.

Amgen is investigating the use of brain-derived neurotrophic factor (BDNF) for treatment of amyotrophic lateral sclerosis (ALS), also known in the US as Lou Gehrig's Disease. The BDNF project is the result of a research collaboration with Regeneron Pharmaceuticals. BDNF is in Phase 2 clinical trials investigating intrathecal administration to determine if it's safe and effective in treating ALS patients. Meanwhile, Regeneron is conducting a Phase 2 study of BDNF delivered subcutaneously in ALS patients.

In addition to naturally occurring neurotrophic factors, Amgen scientists are investigating the therapeutic potential of neuroimmunophilin ligands acquired from Guilford Pharmaceuticals. Neuroimmunophilin ligands belong to a novel class of orally active, small molecule neurotrophic agent that may represent a new treatment for neurodegenerative disorders. The collaboration with Guilford began in 1997 when Amgen licensed worldwide rights for Guilford's FKBP neuroimmunophilins for all therapeutic and diagnostic indications. Amgen and Guilford are investigating treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In preclinical studies, including models of Parkinson's disease, neuroimmunophilins demonstrated potential to promote nerve regeneration and repair. A neuroimmunophilin clinical development program has begun to evaluate use of these compounds in patients with Parkinson's disease.

Amgen has competition from other companies in neuroscience therapeutics but remains confident of its ability to succeed. "Our strengths lie in high quality science combined with speed and efficiency in the development of potential therapeutics from the lab bench to clinical trials," said Amgen's Bruce Altrock, vice president, Research. "As an example, once the leptin gene was cloned, our research teams developed the comprehensive biological information necessary to initiate clinical trials within 18 months."

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