Richard Alan Smith, M.D.

La Jolla, CA

Education and Experience

  • 1958-1961 Brandeis University, Waltham, MA.
  • 1961-1965 Univ. of Miami, School of Medicine, Miami, FL.
  • 1965-1966 Internship (Medicine), Jackson Memorial Hospital, Miami, FL.
  • 1966-1969 Residency (Neurology), Stanford, University Hospital, Palo Alto, CA.
  • 1969-1971 Lt. Commander, U.S. Navy, Head, Neurology Branch, Navy Neuropsychiatric Research Unit, San Diego, CA.
  • 1972-1979 Associate Staff - Neurology* & Microbiology, Scripps Clinic and Research Foundation, La Jolla, CA.
  • 1980-2005 Senior Medical Staff, Scripps Memorial Hospital, La Jolla, California
  • 1979-Present Director, Center for Neurologic Study, La Jolla, CA.
  • 1998-Present Principal Investigator/Sub-Investigator, Coordinated Clinical Research, La Jolla, CA.
  • 1999-2008 Skaggs Clinical Scholar, Scripps Research Institute, La Jolla, CA.
  • 2000-2008 Visiting Scholar, Department of Neuroscience, University of California, San Diego - School of Medicine, La Jolla, CA.  
  • 2005-Present Honorary Medical Staff, Scripps Memorial Hospital, La Jolla, CA.


  • Henry Newman Award - 1968 (San Francisco Neurologic Society)
  • Skaggs Clinical Scholar - 1999-2001 (Scripps Clinic and Research Foundation)

Professional Societies


  • Method for Enhancing the Systemic Delivery of Dextromethorphan for the treatment of Neurological Disorders (5,166,207).
  • Method for Reducing Emotional Lability in Neurologically Impaired Patients (5,206,248).
  • Use of a Cytochrome Oxidase Inhibitor to Increase the Cough-Suppressing Activity of Dextromethorphan (5,350,756).
  • Dextromethorphan and Oxidase Inhibitor for Weaning Patients from Narcotics and Anti-Depressants (6,207,674)
  • Use of Dextromethorphan and an Oxidase Inhibitor to Treat Dermatitis (5,366,980)
  • Dextromethorphan and an Oxidase Inhibitor for Treating Intractable Conditions (5,863,927)
  • Antisense Modulation of Superoxide Dismutase 1, Soluble (SOD-1) Expression (7,678,895)
  • Modulation of Transthyretin Expression for the Treatment of CNS Related Disorders (filed).
  • The Treatment of Motor and Mental Function with Sigma 1 agonists (filed)

Additional Publications (Pre-CNS)

Meinke W., Goldstein D. A., Lancaster W. D., Smith R. A. (1979). Simian Virus 40-Related DNA sequences in a Human Brain Tumor. Neurology 29: 1590.

Meinke W., Smith R. A., Lancaster W. D., Goldstein D. A., Tourtellote W. W. (1977). In Vitro Labelled DNA for Detection of Viral Genomes in Multiple Sclerosis: 1. Papoviruses. Neurology 27: 736.

Hoffmann W., Smith R. A. (1970). Hypokalemic Periodic Paralysis in vitro. Brain 93: 44.

Smith R. A., Norris F. (1975). Symptomatic Care of Patients with ALS. Journal of the American Medical Association 234: 717.

Kohne D. E., Gibbs C. J., White L., Tracy S.M., Meinke W., Smith R. A. (1981). Virus Detection by Nucleic Acid Hybridization: Examination of Normal and ALS Tissues for the Presence of Poliovirus. Journal of General Virology 56: 223.

Smith R. A., Goode R. (1970). Sialorrhea. New England Journal of Medicine 283: 917.

Zir L. M., Smith R. A., Parker D. C. (1970). Human Growth Release in Sleep: Effect of Daytime Exercises. Journal of Clinical Endocrinology and Metabolism 32: 622.

Smith R. A., Johnson L., Rothfeld R., Zir L. M., Tharp B. (1972). Sleep and Cardiac Arrhythmias. Archives of Internal Medicine 130: 751.

Zir L. M., Parker D., Smith R. A., Rossman L. (1972). The Relationship of Human Growth Hormone and Plasma Tyrosine During Sleep. Journal of Clinical Endocrinology and Metabolism 31: 1.

Smith R. A., Dawson A., Foroozan P. (1980). Pharmacologic and Surgical Modalities. The Diagnosis and Treatment of Amyotrophic Lateral Sclerosis, Donald W. Mulder, MD (Ed.), Houghton Mifflin, Professional Publishers, Boston.

Tracy S., Smith R.A. (1981). A Comparison of the Genomes of Polioviruses by cDNA: RNA Hybridization. Journal of General Virology 55: 193.


Smith R. A., Miller T. M. Targeting Neurological Disorders with Antisense Oligonucleotides. In: Crooke S.T., eds. Antisense Drug Technology: Principles, Strategies, and Applications. 2nd ed. Boca Raton, Florida: CRC Press, 2007: 721-745.



Medical Hypotheses (2015) electronic version: Smith R et al. Amyotrophic lateral sclerosis: Is the spinal fluid pathway involved in seeding and spread? 

Meyer K., Ferraiuolo L., Miranda C. J., Likhite S., McElroy S., Renusch S., Ditsworth D., Lagier-Tourenne C., Smith R. A., Burghes A. H., Shaw P. J., Cleveland D. W., Kolb S. J., Kaspar B. K. (2013). Direct Conversion of Patient Fibroblasts Demonstrates Non-cell Autonomous Toxicity of Astrocytes to Motor Neurons in Familial and Sporadic ALS. PNAS 111: 829-832.

Miller T. M., Pestronk A., David W., Rothstein J., Simpson E., Appel S. H., Andres P. L., Mahoney K., Allred P., Alexander K., Ostrow L. W., Shoenfeld D., Macklin E.A., Norris D. A., Manousakis G., Crisp M., Smith R. A., Bennett F. C., Bishop K. M., Cudkowicz M. E. (2013). An Antisense Oligonucleotide Against SOD1 Delivered Intrathecally for Patients with SOD1 Familial Amyotrophic Lateral Sclerosis: A Phase 1, Randomized, First in Man Study. Lancet Neurology 12: 435-442.

Sea K, Gowing G, Joyce N, et al. (2011). ALS in California: a report from the First Annual California ALS Research Summit Neurodegen Dis Management Vol 4: 281-284.

Benson, MD, Smith, RA, Hung, H, Kluve-Beckerman, Showalter, Ad, Sloop, KW, Monia, BP. (2010). Suppression of Choroid Plexus Transthyretin Levels by Antisense Oligonucleotide Treatment. Amyloid Vol 17: 43-49.

Boyajian  R. A., Amo C. A., Otis S. M., Romine J. S., Smith R. A. (2008). Magnetic Source Imaging of Cortical Dysfunction in Amyotrophic Lateral Sclerosis. American Journal of Physical Medicine and Rehabilitation 87: 427-437.

Miller T. M., Smith R. A., Kordasiewicz H., Kasper B. (2008). Gene Targeted Therapies for the Central Nervous System. Archives of Neurology 65: 447-451.

Miller, TM., Smith, RA, Cleveland, DW (2006). Amyotrophic Lateral Sclerosis and Gene Therapy. Nature Clinical Practice Neurology Vol 2: 462-463.

Panitch,HS, Thisted, RA, Smith, RA, Wynn, DA, Wymer, JP, Achiron, A,Vollmer, TL, Mandler, RN, Dietrich, DW, Fletcher, M,  Pope, LE, Berg, JE Miller, A (2006). Randomized, Controlled Trial of Dextromethorphan/Quinidine for Pseudobulbar Affect in Multiple Sclerosis.Annals of Neurology Vol 59: 780-787.

Smith R. A., Miller T. M., Yamanaka K., Monia B. P., Condon T. P., Hung G., Lobsiger C. S., Ward C. M., McAlonis-Downes M., Wei H., Wancewicz E. V., Bennett C. F., Cleveland D. W. (2006). Antisense Oligonucleotide Therapy for Neurodegenerative Disease. Journal of Clinical Investigation 116: 2290-2296.

Smith, RA. (2006). Dextromethorphan/Quinidine: A Novel Dextromethorphan Product for the Treatment of Emotional Lability. Expert Opinion on Pharmacotherapy Vol 7: 2581-2598.

Brooks B. R., Thisted R. A., Appel S. H., Bradley W. G., Olney R. K., Berg G. E., Pope L. E., Smith R. A. (2004). Treatment of Pseudobulbar Affect in ALS with Dextromethorphan/Quinidine. Neurology 63: 1364-1370.

Smith, RA, Berg, J., Callahan, J., and Pope, L. (2004). Validation of the CNS Emotional Lability Scale in Multiple Sclerosis Patients. Multiple Sclerosis Vol 10: 679–685.

Smith, R.A., Berg, J., Pope, L., and Thisted, R.A. (2004). Measuring Pseudobulbar Affect in Amyotrophic Lateral Sclerosis. ALS Journal.  Michael Swash (Ed), London, UK.  Vol 5:  99-102.

Wilson, J.M.B., Khabazian, I., Wong, M.C., Seyedalikhani, A., Bains, J.S., Pasqualotto, B.A., Williams, D.E., Andersen, R. J., Simpson, R.J., Smith, R., Craig, U-K., Kurland, L, Shaw, C.A. (2002). Behavioral and Neurological correlates of ALS-Parkinsonism Dementia Complex in Adult Mice Fed Washed Cycad Flour. Neuro-Molecular Medicine Vol 1: 207-221.

Armon C., Graves M. C., Moses D., Forte D. K., Darby S. M., Smith R. A. (2000). Linear Estimates of Disease Progression Predict Survival in Patients With ALS. Muscle and Nerve 23: 874-882.

Smith, R.A. (2000) Effect of the Early Diagnosis of Amyotrophic Lateral Sclerosis on the Patient: disadvantages. Amyotrophic Lateral Sclerosis Vol 1: 75-77.

BDNF Study Group (Phase III) (1999). A Controlled Trial of Recominant Methionyl Human BDNF in ALS. Neurology 52: 1427-1433.

Smith R. A, Licht J. (1999). Neuromuscular Disease. Current Practice of Medicine. Bone R.C. (Editor). Philadelphia: Current Medicine, Inc., pp. 807-817.

Wilson D. B., Smith R. A., Golding A., Nelson J. R., Smith L., Carlo D. J., Brostoff S. W., Gold D.P. (1997). Results of a Phase I Clinical Trial of a T Cell Receptor Peptide Vaccine in Patients with Multiple Sclerosis. I. Analysis of T Cell Receptor Utilization in CSF Cell Populations. Journal of Neuroimmunology 76: 15-28.

Moore S. R., Gresham L.S., Bromberg M., Kasarkis E.J., Smith R.A. (1997). A Self Report Measure of Affective Lability. Journal of Neurology, Neurosurgery and Psychiatry 63: 89-93.

Gold D. P., Smith R. A., Golding A., Nelson J. R., Dively J., Laxer J., Richieri S., Carlo D. J., Brostoff  S. W., Morgan E., Wilson D. B. (1997). Results of a Phase I Clinical Trial of a T Cell Receptor Vaccine in Patients with Multiple Sclerosis. I. Comparative Analysis of TCR Utilization in CSF T Cell Populations Before and After Vaccination with a TCRVB6 CDR2 Peptide. Journal of Neuroimmunology 76: 15-28.

Feenberg, A.L, Licht, J.M., Kane, K.P., Moran, K., Smith, R.A. (1996). The online patient meeting. J of Neurological Sciences Vol 139: 129-131.

Smith R. A., Balis F. M., Ott K. H., Elsberry D. D., Sherman M. R., Saifer M. G. P. (1994). Pharmacokinetics and Tolerability of Ventricularly Administered Superoxide Dismutase in Monkeys and Preliminary Clinical Observations in Familial ALS. Journal of the Neurological Sciences 129: 13-18.

Smith R. A., Licht J. M., Manley P. E., Girten B., Tuttle R. (1994). Testing the Limits of Palliative Care. ALS-"From Charcot to the Present and into the Future." Rose F. C. (Editor). London: Smith-Gordon & Company Ltd., pp. 315-324.

Gresham, L.S., Molgaard, C.A., Smith, R.A. (1993).  Induction of Cytochrome P-450 Enzymes via Tobacco Smoke: A Potential Mechanism for Developing Resistance to Environmental Toxins as Related to Parkinsons and Other Neurologic Diseases. Neuroepidemiology 12: 114-116.

Smith R. A., Melmed S., Sherman B., Frane J., Festoff B. (1993). Double Blind Experimental Treatment Trial Using Recombinant Human Growth Hormone in Amyotrophic Lateral Sclerosis. Muscle and Nerve 16: 624-633.

Zhang Y., Britto M. R., Valderhaug K. L., Wedlund P. J., Smith R. A. (1992). Dextromethorphan: Enhancing its Availability Via Quinidine Mediated Inhibition of Cytochrome P450-2D6. Journal of Clinical Pharmacology & Therapeutics 51:647-655.

Smith R. A., Valderhaug K. L., Wedlund P. J. (1990). The Excitotoxin Hypothesis: Therapeutic Considerations in Amyotrophic Lateral Sclerosis. Motor Neurone Disease. Rose C., Norris F. H. (Editors). London: Smith-Gordon Publishers, pp. 287-293.

Eldon M. A., Smith R. A., Leese P. T., Daigle A. E., Katy D. V., Richieri S. P. (1990). Safety and Tolerability of Single Intravenous Doses of T Cell Modulatory Peptide (TCMP-80) in Healthy Volunteers. Journal of Clinical Pharmacology 30: 352-357.

Smith R. A., Norris F. H. (1988). The Treatment of Amyotrophic Lateral Sclerosis with Interferon. Interferon Treatment of Neurologic Disorders. Smith R. A. (Editor). New York: Marcel Dekker, pp. 265-276.

Wills R. J., Smith R. A. (1988). Pharmacokinetics of Interferons. Interferon Treatment of Neurologic Disorders. Smith R. A. (Editor). New York: Marcel Dekker, pp. 103-133.

Lakshmanan, J., Burns, C., Smith, R.A. (1988) Molecular forms of Nerve Growth Factor in Mouse Submaxillary Glands. Biochem. & Biophys. Research Communications Vol 152: 1008-1014.

Smith R. A., Norris F. (1987). Caring for Patients with Amyotrophic Lateral Sclerosis.Psychosocial Aspects of Muscular Dystrophy and Allied Diseases. Carash L., Lovelace R. (Editors). Springfield: Charles C. Thomas Publishers, pp. 23-30.

Greesham L. S., Moolgard C. A., Golbeck A. L., Smith R. A. (1987). Amyotrophic Lateral Sclerosis and History of Skeletal Fracture: A Case Study. Neurology 37: 717-719.

Gresham L. S., Molgaard C. A., Golbeck A. L., Smith R. A. (1986). Amyotrophic Lateral Sclerosis and Occupational Heavy Metal Exposure: A Case-Control Study. Neuroepidemiology 5: 29-38.

Panitch H. S., Gomez J., Norris F. H., Cantell K., Smith R. A. (1986). Remission of Subacute Sclerosing Panencephalitis in Patients Treated with Intraventricular Interferon. Neurology 36: 562-566.

Norris F. H., Smith R. A., Denys E.H. (1985). Motor Neuron Disease: Towards Better Care. British Medical Journal 291: 259-262.

Smith R. A., Norris F., Palmer D., Bernhardt L., Wills R. J. (1985). Distribution of Alpha Interferon in Serum and Cerebrospinal Fluid After Systemic Administration. Journal of Clinical Pharmacology and Therapeutics 37: 85-88.

Brahic M., Smith R. A., Gibbs C. J., Garruto R. M., Tourtellotte W. W., Cash E. (1985). Detection of Picornavirus Sequences in Nervous Tissue of Amyotrophic Lateral Sclerosis and Control Patients. Annals of Neurology 18: 337-343.

Cudkowitz M. E., Brown R. H., Smith R. A. (1998). Free Radical Toxicity in Amyotrophic Lateral Sclerosis. Glutathione in the Nervous System. Shaw C. A. (Editor). New York: Taylor & Francis, pp. 343-353.

Smith R. A., Gillie E., Licht L. (1991). Palliative Treatment of Motor Neuron Disease. Handbook of Clinical Neurology. Diseases of the Motor System. De Jong J. M. B. V. (Editor). Amsterdam: Elsevier Science Publishers, pp. 459-473.

Smith R. A. (1991). Experimental Treatment of Amyotrophic Lateral Sclerosis. Handbook of Amyotrophic Lateral Sclerosis.  Smith R. A. (Editor). New York: Marcel Dekker, p. 317-343.

Smith R. A., Jacoby S., Festoff B., Melmed S., Frane J., Sherman B. (1990). The Influence of Compliance and Other Human Factors On Treatment Trials. Methodological Problems in ALS Trials. Rose F. D. (Editor). New York: Demos Publications.

Margolis R. S., Whitten R., Rauch C. T., Hassain H., Smith R. A. (1988). Characterization of Microtubule Associated Proteins in Amyotrophic Lateral Sclerosis. Amyotrophic Lateral Sclerosis, Research Aspects. Tsubake T., Yase Y. (Editors). Amsterdam: Elsevier Science Publishers, pp. 325-332.

Smith R. A., Landel C. P., Cornelius C. E. and Revel M. (1987). Mapping the Action of Interferon on Primate Brain. The Biology of the Interferon System, 1986 - Proceedings of the 1986 TNO-ISIR Congress. Cantell K., Schellekens H. (Editors). Amsterdam: Elsevier Science Publishers, pp. 563-566.

Smith R. A. (1987). On Behalf of the Patient. Research, Psychological and Treatment Aspects of ALS. Amsterdam: Elsevier Science Publishers, pp. 319-322.

Smith R. A., Norris F.H. (1987). Antiviral Therapy. Research, Psychological and Treatment Aspects of ALS. Charash L., Lovelace R. (Editors). Amsterdam: Elsevier Science Publishers, pp. 297-304.

Smith R. A., Abramsky O., Steiner I., Panitch H., Cantell K. (1986). The Experimental Treatment of Subacute Sclerosing Panencephalitis with Interferon. The Biology of the Interferon System. Stewart W. E., Schellekens H. (Editors). Amsterdam: Elsevier Science Publishers.

Salazar A. M., Gibbs C. J., Gajdusek D. C., Smith R. A. (1984). Clinical Usage of Interferons: Central Nervous System Disorders. Interferons and Their Applications. Handbook of Experimental Pharmacology. Came P. E., Carter W. A. (Editors).

ALS CNTF Treatment Study [ACTS] Study Group, A Double-Blind Placebo-Controlled Clinical Trial of Subcutaneous Recombinant Human Ciliary Neurotrophic Factor (rHCNTF) in Amyotrophic Lateral Sclerosis, (1996). Neurology 46:1244-1249.