Examples of the Advancement of Clinical Neuroscience Since 1992

neurological update P> In the early spring of 1992, 32 basic and clinical neuroscientists met at the Cold Spring Harbor New York Laboratories under the auspices of the Dana Foundation and the leadership of James Watson. The purpose was to choose 10 of the most important neurological diseases waiting to be solved during the remaining eight years of the Decade of the Brain. The predicted findings (bold face) and some of the actual achievements (plain print) are listed below.

1. Identification of genes for familial Alzheimer’s and Huntington’s diseases.

• AD: The precursor protein gene on Cr21; the apoprotein gene on Cr19; the Presenilin gene 1 on Cr14; and the Presenilin 2 on Cr1.

• HD: The gene producing normal huntinin on Cr4 naturally generates 11-34 CAG (glutamine) repeats, whereas abnormal huntintin generates 40-120 repeats and produces the disease. Seven other genetic disorders also possess an excess of unstable CAG repeats.

2. Specific gene identification of manic-depressive illness: None.

3. Development of new medications and therapeutic strategies for stroke and other forms of brain injury.

• For acute stroke treatment: TPA for stroke prevention: treat early hypertension; treat atherosclerotic auricular fibrillation with coumadin; other approaches only experimental.

4. Develop new drugs for multiple sclerosis; Alzheimer’s disease; motor neuron disease; Parkinson’s disease; epilepsy.

• Multiple sclerosis: beta-interferon, copolymer A. AD: Aricept, estrogens, NSAIDS-VIT E.

• MND: Riluzole. PD: new drugs; partial pallidotomy; deep brain stimulation of the pallidum or the subthalamic nucleus; selective fetal implants. EPI: Seven new drugs, vagal stimulation.

5. Identify new treatments to promote nerve regeneration following spinal and peripheral nerve injury.

• Growth factors ineffective; favorable neuronal repair by stem cells injected into traumatic spinal cord.

6. Develop new and more effective treatments for manic-depressive illness, anxiety disorder, and forms of schizophrenia that presently resist treatment.

• Several new agents bring modest improvements, none spectacular.

7. Discovery, testing, and application of agents that would block the action of cocaine and other addictive substances. Only experimental data available.

8. Development of new treatments for pain associated with cancer, arthritis, migraine headache, and other debilitating illnesses.

• New approaches ameliorate cancer pain, migraine, central and other pains; readjustments of opiates for cancer pain; deep surgical stimulation of thalamic and motor cortex areas may relieve other pain.

9. Identification of genes that cause hereditary deafness or blindness.

• Many genes have been identified, more are still being discovered.

10. Elucidation of the neural mechanisms involved in learning and memory.

• Memory found to encompass many dimensions: long vs. short; instinctive vs. learned; cognitive vs. spatial; short vs. immediate. No immediate memory = no awareness.

Commentary

The high percentage of predicted discovery among the above targets indicates how rapidly clinical neuroscience is developing as the century opens and proceeds. Pain amelioration is likely to improve due to ingenious targeting of specific pharmacologic agents directed against particular types of pain. I suspect that highly selected neurosurgical treatments may return from a not very flourishing present industry to do the same. Top of the effort, of course, is to identify the presumed genetic mixtures that underlie bipolar disorder as well as the several forms of schizophrenia. In the meantime at least, new drugs may help, but most of the present ones seem to relate to fairly similar templates. Neurology Alert hopes we can get the information to our readers as soon as confirmed. (I thank the Dana Foundation and Joseph B. Martin, MD, PhD, of Harvard Medical School [see Martin JB. N Engl J Med 1999;340:1970-1980], for assistance in gathering information about this material.) —fp