Correspondence

Protective Effect or Symptomatic Effect of Deprenyl?

N Engl J Med 1993; 328:1715June 10, 1993

Article

To the Editor:

Is it not time to read between the lines? The recent partial retraction of the preliminary, enthusiastic report after additional follow-up by the Parkinson Study Group (Jan. 21 issue)1 has greatly diminished the previous claims of a protective effect of deprenyl in patients with early untreated Parkinson's disease and has enhanced the known symptomatic effect of this agent2,3.

Many obvious questions remain. Why have the results of objective biochemical studies related to the predicted attenuation of cerebrospinal fluid homovanillic acid that was an important part of the initial protocol4 not been revealed? Have these findings not conformed to the initial expectations?

Since the new study1 essentially discards the presumed antioxidant effect of tocopherol in early Parkinson's disease, we are compelled to reevaluate the free-radical hypothesis5. Other indications of backtracking include the recommendation that “deprenyl should be considered among the available therapeutic options for the initial treatment of early Parkinson's disease”1. The authors also note that “Previous studies have suggested that deprenyl has a protective effect, . . . but this assertion has not yet been established.” Furthermore, they state, “The lack of conclusive evidence of a neuroprotective effect of deprenyl justifies further placebo-controlled trials of other promising agents.”

Oscar S. Kofman, M.D.
University of Toronto, Toronto, ON M5R 2G5, Canada

5 References

1. 1

   The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1993;328:176-183
   Full Text | Web of Science | Medline

2. 2

   Kofman OS. Deprenyl: protective vs. symptomatic effect. Can J Neurol Sci 1991;18:83-85
   Web of Science | Medline

3. 3

   Schulzer M, Mak E, Calne DB. The antiparkinson efficacy of deprenyl derives from transient improvement that is likely to be symptomatic. Ann Neurol 1992;32:795-798
   CrossRef | Web of Science | Medline

4. 4

   Parkinson Study Group. DATATOP: a multicenter controlled clinical trial in early Parkinson's disease. Arch Neurol 1989;46:1052-1060
   Web of Science | Medline

5. 5

   Calne DB. The free radical hypothesis in idiopathic parkinsonism: evidence against it. Ann Neurol 1992;32:799-803
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Shoulson replies:

To the Editor: Dr. Kofman makes several points about our report and draws several inferences. Our analyses of cerebrospinal fluid homovanillic acid are the subject of a separate, peer-reviewed report1. As we indicated, treatment with tocopherol, which traps peroxyl radicals and interrupts the chain reaction of lipid peroxidation, may be less effective than other antioxidative interventions that prevent the formation of cytotoxic radicals and the initiation of lipid peroxidation2. The failure of tocopherol to slow the progression of disability or influence the clinical features of Parkinson's disease does not exclude a possible role of free radicals in this disorder3.

On the basis of our accumulated data and most recent analyses, we have indeed revised our recommendations about the use of deprenyl as monotherapy for early Parkinson's disease and have emphasized the justification for further placebo-controlled trials of other promising neuroprotective agents. We take exception to the tone of Dr. Kofman's comments. Our report should not be misconstrued as a retraction, a term that implies deceptive or fraudulent data. We stand by the integrity of our trial and our peer-reviewed publications.

Ira Shoulson, M.D. (Principal Investigator, M.D. (Principal Investigator, DATATOP)
University of Rochester, Rochester, NY 14642

for the DATATOP Steering Committee on behalf of the Parkinson Study Group

3 References

1. 1

   Parkinson Study Group. The DATATOP Study: cerebrospinal fluid homovanillic acid changes in patients with mild, early parkinsonism. Mov Disord (in press).
   

2. 2

   Haliwell B, Gutteridge JMC. Oxygen radicals and the nervous system. Trends Neurosci 1985;8:22-26
   CrossRef | Web of Science

3. 3

   Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson's disease: evidence supporting it. Ann Neurol 1992;32:804-812
   CrossRef | Web of Science | Medline

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