LETTERS:
PUBLISHED
50 Years of Levodopa I read with great deal of interest the articles published in the LEVODOPA Special Issue of Movement Disorders, vol. 30, No.1 (2015), in particular the historical essays on: A. Carlsson; myself (both by A. Lees); G. Cotzias (by E. Tolosa); and M. D. Yahr (by W. Olanow), as weIl as the review of the L-dopa story by S. Fahn, and I wish to thank the authors and congratulate the Guest Editors Stanley Fahn and Wemer Poewe for this fine publication. As regards my own involvement in the L-dopa story, I was pleasantly surprised how clearly, in most instances, I could recognize myself as one of the four presented actors in this DA/PD/LD drama, and for this I express my deep gratitude to all the above-named authors. The one instance on which I wish to express, by permission, my disagreement concerns the interpretation, in the articles by Fahn and by Olanow, of what I wrote 50 y ago about the at that time not yet settled question concerning the therapeutic value of L-dopa in Parkinson’s disease, which was “. . . in my opinion mainly due to the fact that because of the unpleasant side effects of L-dopa, it is practically impossible to inject [i.v.] doses of the drug, which are high enough to increase the dopamine levels in the striatum.”1 From this statement, written by me in 1965, and prominently referred to by both Fahn and Olanow in their respective articles, the authors jump to the surprising conclusions that “. . . even Hornykiewicz felt that treatment with L-dopa was impractical” (Fahn, p. 12, column 1, bottom), and that “. . . Hornykiewicz, himself, considered the drug to be primarily of theoretical interest” (Olanow, p. 33, column 1, line 17 from bottom). I do not think that it is possible to draw such conclusions from my above-quoted wording, which is clearly directed to the practical issue of the greatly unfavorable “dose-to-side effects” ratio of injected [!] L-dopa, thus prohibiting use of higher (intravenous!) doses; a problem George Cotzias solved by the slowly increasing high oral (D)L-dopa regimen that he introduced 2 y later (1967)—not without full knowledge as well as acknowledgement of our earlier neurochemical post-mortem and clinical studies. 1
Oleh Hornykiewicz, MD1 Center for Brain Research, Spitalgasse 4, A-1090 Vienna, Austria
-----------------------------------------------------------*Correspondence to: Oleh Hornykiewicz, MD, Center for Brain Research, Spitalgasse 4, A-1090 Vienna, Austria, e-mail: [email protected]
Relevant conflicts of interest/financial disclosures: Nothing to report. Received: 9 March 2015; Accepted: 19 March 2015 Published online 21 May 2015 in Wiley Online Library (wileyonlinelibrary.com). Doi: 10.1002.mds.26240
1008
Movement Disorders, Vol. 30, No. 7, 2015
ARTICLES
Reference 1.
Hornykiewicz, O. Metabolism of brain dopamine in human parkinsonism: neurochemical and clinical aspects. In: Costa E, Cote LJ, Yahr MD, eds. Biochemistry and Pharmacology of the Basal Ganglia. New York: Raven Press; 1966:171-181.
Reply: Oleh Hornykiewicz’s Contribution to the L-dopa Story I am gratified that Dr. Hornykiewicz read with great interest the special issue on levodopa (L-dopa) published in January this year.1 Without his numerous contributions, there may never have been an L-dopa story to tell. For me, there is a personal side to the story because Dr. Hornykiewicz was instrumental in my involvement with Parkinson’s disease (PD) and other basal ganglia disorders. In 1965 I had just become a junior faculty member at Columbia University. A few months later, at a Columbia symposium, Dr. Hornykiewicz delivered a talk on his findings of low dopamine concentrations in the brains of people who died with PD.2 I was so awe-struck listening to his talk and hearing the results of his research that at that singular moment during the symposium I decided to shift my research career from the biochemistry of the sodium pump to the biochemistry of the basal ganglia. Fortunately, I have been able to mention this “epiphany” to Dr. Hornykiewicz personally, so he knows how indebted I am to him. In his Letter to the Editor, Dr. Hornykiewicz comments that in my article3 I misinterpreted the following statement in the written report of his 1965 remarks2: “the question as to the therapeutic value of L-dopa in parkinsonism seems still to be unsettled . . . because of the unpleasant side effects.. . .” In my review, I interpreted this to mean that “treatment with L-dopa was impractical,” intending to make the point that as late as 1965, L-dopa therapy was not an accepted therapeutic approach for PD. As Dr. Hornykiewicz says in his letter, he was referring to intravenous injections of L-dopa (an approach he and Walther Birkmayer had pursued). He had no way of knowing in 1965 that 2 y later, high doses of orally administered L-dopa by George Cotzias would
-----------------------------------------------------------*Correspondence to: Dr. Stanley Fahn, MD, Columbia University College of Physicians and Surgeons, 710 West 168th Street, New York, NY 10032, USA, e-mail: [email protected] Funding agencies: None. Relevant conflicts of interest/financial disclosures: Nothing to report. Received: 16 March 2015; Accepted: 19 March 2015 Published online 16 April 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.26242
PUBLISHED
50 Years of Levodopa I read with great deal of interest the articles published in the LEVODOPA Special Issue of Movement Disorders, vol. 30, No.1 (2015), in particular the historical essays on: A. Carlsson; myself (both by A. Lees); G. Cotzias (by E. Tolosa); and M. D. Yahr (by W. Olanow), as weIl as the review of the L-dopa story by S. Fahn, and I wish to thank the authors and congratulate the Guest Editors Stanley Fahn and Wemer Poewe for this fine publication. As regards my own involvement in the L-dopa story, I was pleasantly surprised how clearly, in most instances, I could recognize myself as one of the four presented actors in this DA/PD/LD drama, and for this I express my deep gratitude to all the above-named authors. The one instance on which I wish to express, by permission, my disagreement concerns the interpretation, in the articles by Fahn and by Olanow, of what I wrote 50 y ago about the at that time not yet settled question concerning the therapeutic value of L-dopa in Parkinson’s disease, which was “. . . in my opinion mainly due to the fact that because of the unpleasant side effects of L-dopa, it is practically impossible to inject [i.v.] doses of the drug, which are high enough to increase the dopamine levels in the striatum.”1 From this statement, written by me in 1965, and prominently referred to by both Fahn and Olanow in their respective articles, the authors jump to the surprising conclusions that “. . . even Hornykiewicz felt that treatment with L-dopa was impractical” (Fahn, p. 12, column 1, bottom), and that “. . . Hornykiewicz, himself, considered the drug to be primarily of theoretical interest” (Olanow, p. 33, column 1, line 17 from bottom). I do not think that it is possible to draw such conclusions from my above-quoted wording, which is clearly directed to the practical issue of the greatly unfavorable “dose-to-side effects” ratio of injected [!] L-dopa, thus prohibiting use of higher (intravenous!) doses; a problem George Cotzias solved by the slowly increasing high oral (D)L-dopa regimen that he introduced 2 y later (1967)—not without full knowledge as well as acknowledgement of our earlier neurochemical post-mortem and clinical studies. 1
Oleh Hornykiewicz, MD1 Center for Brain Research, Spitalgasse 4, A-1090 Vienna, Austria
-----------------------------------------------------------*Correspondence to: Oleh Hornykiewicz, MD, Center for Brain Research, Spitalgasse 4, A-1090 Vienna, Austria, e-mail: [email protected]
Relevant conflicts of interest/financial disclosures: Nothing to report. Received: 9 March 2015; Accepted: 19 March 2015 Published online 21 May 2015 in Wiley Online Library (wileyonlinelibrary.com). Doi: 10.1002.mds.26240
1008
Movement Disorders, Vol. 30, No. 7, 2015
ARTICLES
Reference 1.
Hornykiewicz, O. Metabolism of brain dopamine in human parkinsonism: neurochemical and clinical aspects. In: Costa E, Cote LJ, Yahr MD, eds. Biochemistry and Pharmacology of the Basal Ganglia. New York: Raven Press; 1966:171-181.
Reply: Oleh Hornykiewicz’s Contribution to the L-dopa Story I am gratified that Dr. Hornykiewicz read with great interest the special issue on levodopa (L-dopa) published in January this year.1 Without his numerous contributions, there may never have been an L-dopa story to tell. For me, there is a personal side to the story because Dr. Hornykiewicz was instrumental in my involvement with Parkinson’s disease (PD) and other basal ganglia disorders. In 1965 I had just become a junior faculty member at Columbia University. A few months later, at a Columbia symposium, Dr. Hornykiewicz delivered a talk on his findings of low dopamine concentrations in the brains of people who died with PD.2 I was so awe-struck listening to his talk and hearing the results of his research that at that singular moment during the symposium I decided to shift my research career from the biochemistry of the sodium pump to the biochemistry of the basal ganglia. Fortunately, I have been able to mention this “epiphany” to Dr. Hornykiewicz personally, so he knows how indebted I am to him. In his Letter to the Editor, Dr. Hornykiewicz comments that in my article3 I misinterpreted the following statement in the written report of his 1965 remarks2: “the question as to the therapeutic value of L-dopa in parkinsonism seems still to be unsettled . . . because of the unpleasant side effects.. . .” In my review, I interpreted this to mean that “treatment with L-dopa was impractical,” intending to make the point that as late as 1965, L-dopa therapy was not an accepted therapeutic approach for PD. As Dr. Hornykiewicz says in his letter, he was referring to intravenous injections of L-dopa (an approach he and Walther Birkmayer had pursued). He had no way of knowing in 1965 that 2 y later, high doses of orally administered L-dopa by George Cotzias would
-----------------------------------------------------------*Correspondence to: Dr. Stanley Fahn, MD, Columbia University College of Physicians and Surgeons, 710 West 168th Street, New York, NY 10032, USA, e-mail: [email protected] Funding agencies: None. Relevant conflicts of interest/financial disclosures: Nothing to report. Received: 16 March 2015; Accepted: 19 March 2015 Published online 16 April 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.26242
