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Embargo by The Lancetz
Friday, July 1, 1994,7:00p.m. EasternDaylightTime
For information:
Robin B. Goldsmith
(619)554-8134
Media Advisory
#o70194
Scientists at The Scripps ResearchInstitute Demonstrate
that Powerful Anti-Lymphocyte Drug Favorably Influences
the Course of Chronic ProgressiveMS
Cladribine showspromise as a therapy for the disorder.
What:
A teamof researchers
led by ErnestBeutler, M.D., has reportedin this
week's issueof rhe Lancetthat cladribine, or 2-chlorodeoxyadenosine
(2-CdA), a powerful anti-lymphocytedrug developedand testedat The
ScrippsResearchInstitute (TSRI), has been shown to favorably influence the
courseof chronicprogressivemultiple sclerosis(MS) and showspromiseas
a therapyfor the disease.
The useof the dnrg for MS was consideredby scientistsafter extensive
experiencewith the dnrg in the successfultreaunentof lymphoid leukemias,
particularlyhairy cell leukemia.
Who:
Dr. Beutler is Chairmanof the Deparunentof Molecular and Experimental
Medicineat TSRI and a memberof the National Academyof Sciences.
Additionalauthorsof the study, entitled "Effectivenessof Cladribinein the
Treatmentof ChronicProgressiveMultiple Sclerosis,"are Jack C. Sipe,
M.D., Divisionof Neurology,ScrippsClinic; JohnS. Romine,M.D.,
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CLADRIBII\E
Divisionof Neurology,ScrippsClinic; JamesA. Koziol, Ph.D.,
biostatistician,Deparftnentof Molecular and ExperimentalMedicine, TSRI;
RobertMcMillan, M.D., Departmentof Molecular and Experimental
Medicine,TSRI; and JackZyroff, M.D., Division of Neuroradiology,
ScrippsClinic.
Background: Multiple sclerosisaffectsapproximately300,000peoplein the U.S. Of
these,upwardsof one-halfsuffer from chronic progressivemultiple
sclerosis,a severelydisablingdiseaseof the centralnervoussystemthat
involvesthe destructionof the insulatingsheath,or myelin, that coversthe
nervefibers. Muscle coordination,visual sensationand other signalsare
slowedor blocked.Patientswith the diseasesuffer from fatigue, difficulty
walking, spasticity,muscleweakness,tremor and impairedthinking and
reasoning.Somepatientsdevelopcompleteparalysis.
While the causeof MS is unknown, many researchers
believethat
autoimmunemechanismsplay an importantrole, theorizingthat white blood
cells of the immune systemattack the myelin sheaththat insulatesthe
nerves. Cladribine was testedin this study to determinewhether selective
lymphocytedepletioncould slow or halt clinical diseaseprogressionand
allow patientsto improve.
The Study:
Forty-eightchronicprogressiveMS patientsparticipatedin a double-blind,
placebo-controlled
study of the effectivenessof 2-CdA administeredby
centralvenouscatheter.Patientswere pairedby age, sex, durationand
severity of the disease.Twenty-four patientswere randomizedto four
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CLADRIBIIYE
monthly infusions of the drug, while the other 24 were given saline solution.
Becauseof the positiveresultsat one year, the formal study was terminated
and the placebogroup wastreatedwith one-halfthe doseof 2-CdA given to
patientsduring the first year of the study.
At monthly examinations,the patients'levelsof neurologicdisability were
measuredby standardrating scales.In addition,the spinalfluid was testedto
measureimmune activity and the volume of brain lesionswas determinedby
magneticresonanceimaginginitially and at six, 12, 18 and 24 months.
Cladribineuse was associated
with a highly significantdifferencein
neurologic rating scores.The neurologic statusof patientsgiven Cladribine
was slightly improvedor stabilized;patientsgiven the placebocontinuedto
manifesta declineof neurologicstatus.Further, the total volume of MS
brain lesionsdecreased
in patientstreatedwith Cladribine.In addition, there
was a signficant differencein the spinal fluid findings of patientsreceiving
Cladribineand thosereceivin! the placebo,suggestingdecreased
autoimmuneactivity in responseto Cladribine.
A multi-center trial will be implementedsoonunder the leadershipof the
Scrippsgroup. This trial will make the experimentaltreafinentavailable to
eligible patientsin variouspartsof the country.
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