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From chemical to drug: neurodegeneration drug screening and the ethics of clinical trials

Nature Neuroscience volume 5, pages 1027–1029 (2002)Cite this article

Neuroscientists—increasingly optimistic about finding new treatments for neurological disorders—are beginning to propose promising drugs for clinical testing. Just in the last year, for example, more than 30 laboratories have tested collections of FDA-approved drugs in simple models of neurodegeneration1,2,3,4. In one case, a consortium of 26 laboratories compared the effects of 1040 such compounds for their effects in biochemical, cellular and invertebrate models of neurodegenerative diseases, including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy4. These systematic screens have yielded compounds with activity in vitro and in model organisms such as Drosophila and C. elegans. Some targets of these screens represented suspected mechanisms of neurodegeneration, such as changes in protein conformation1, protein aggregation4 or RNA splicing2,4, whereas other targets were 'phenomenological', such as preventing the death of neuronal cells in culture or in an invertebrate nervous system4. The compounds identified offer promise of benefit to people at genetic risk for neurodegenerative disorders or already suffering from such a disease.

Ironically, the proliferation of candidate drugs has often brought more angst than excitement. Faced with a positive result from an in vitro screen, researchers become entangled in a difficult scientific and ethical question: how much do they need to know before proposing a clinical trial? There is often an assumption among scientists that further experimentation must remove all doubt before a drug is tried in patients. Unfortunately, imposing this condition would almost certainly prevent any drugs from ever reaching the clinic.

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Authors and Affiliations

  1. the Technology Development Program, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, 20892, Maryland, USA

    Jill Heemskerk

  2. the Brain Research Institute, University of California, Los Angeles, 90095, California, USA

    Allan J. Tobin

  3. the Clinical Trials Program, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, 20892, Maryland, USA

    Bernard Ravina

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  1. Jill Heemskerk
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  2. Allan J. Tobin
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  3. Bernard Ravina
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Correspondence to Jill Heemskerk.

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Heemskerk, J., Tobin, A. & Ravina, B. From chemical to drug: neurodegeneration drug screening and the ethics of clinical trials. Nat Neurosci 5 (Suppl 11), 1027–1029 (2002). https://doi.org/10.1038/nn931

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