3
39.Pll 30-Month Results of Foetal Dopamine Cell Transplantation into the Brains of Parldnsonian Patients J. Dymecki , M. Zabek2, W. Mazurowski2, W. Lechowicz , J. Stelma-Ch w 3 and E. Zawada 3 1Department of Neuropathology, Institute of Psychiatry and Neurology, Warsaw; 2Department of Neurosurgery and 3Department of Obstetrics-Gynecology, District Hospital, Warsaw, Poland 325 After many years of experimental studies we obtained permission in 1988 from the Research Ethical Committee of the Medical Academy in Warsaw to perform a series of therapeutic transplantations of human foetal mesencephalic tissue into the brains of patients with Parkinson’s disease (PD). We followed NECTAR ethical guidelines for the use of foetal material for transplantation purposes. Implantations of human foetal dopaminergic cells taken from the ventral part of one mesen- cephalon of 11-12 week-old foetuses into the head of the caudate nucleus were performed in three PD patients aged 48, 53, and 50 years, respectively. All patients had been suffering from the severe form of PD for about 10-15 years (stage 4/5 according to Hoehn & Yahr scale) with bradykinesia, rigidity and tremor as the main symptoms. Long-lasting L-dopa ther- apy resulted in side effects with "ON-OFF" syndrome and dyskinesias. The operations were performed according to Madrazo’s microsurgical technique. Implanta- tion of foetal tissue into the caput of the caudate nucleus was carried out by means of an instru- ment devised by Zabek. One day before the operation immunosuppressive therapy was introduced and continued for 6 postoperative months. A detailed clinical examination was performed before and every 3 months after the operation according to the battery of inter- national tests recommended by CAPIT. The patients were under post-operational observation lasting 30, 20 and 12 months, respectively. Improvement was observed in all patients starting between 3 and 6 months after operation until the present. Significant increases in movement speed for repeated pronation- supination, finger dexterity and foot lifting tests were found. The speed of walking also increased with decreased rigidity. The "OFF" phase during the day became shorter and less severe; dys- kinesias were markedly reduced. Some of the results obtained during the 30-month recovery of patient No. 1 are presented in the following Figure and Table. It seems that the 30 and 20 months recovery of patients No. 1 and No. 2, respectively, is a long enough term of observation to recommend the benefits of intracerebral transplantations in hopeless patients, who have already exhausted all the other therapeutic possibilities and are conscious that the course of the disease will slowly progress and deteriorate. In all patients recovery was not observed before 3 months after transplantation. Probably, this period of time is necessary for sprouting and creation of a neuronal network between the graft and the host brain. The improvement increased between the 3rd and 6th months, was still continuing during the following months and reached a stable stage at 9-12 months after the transplantation. Despite the fact that the doses of L-dopa could not be decreased we observed that the duration of dyskinesias and OFF phase de- creased significantly in all cases. It is also worth noting that despite the unilateral DA cell im- plantation, bilateral motor improvement was found. Our results indicate that foetal grafting seems to be a valuable method for selected parkinsonian patients. However, we should never forget that at present neural transplanta- tion is still an experimental approach. (C) FREUND PUBLISHING HOUSE LTD., LONDON. JOURNAL OF NEURAL TRANSPLANTATION & PLASTICYrY, Vol. 3, No. 4,1992

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Page 1: 30-Month ResultsofFoetal Cell into the Brains of ...downloads.hindawi.com/journals/np/1992/721764.pdf · Pronationsupination Fingerdexterity EFFECT "OFF"phase duringtheday(%) Durationof

39.Pll

30-Month Results of Foetal Dopamine Cell Transplantationinto the Brains of Parldnsonian Patients

J. Dymecki, M. Zabek2, W. Mazurowski2, W. Lechowicz, J. Stelma-Ch w3 and E. Zawada3

1Department ofNeuropathology, Institute ofPsychiatry and Neurology, Warsaw; 2Department ofNeurosurgery and 3Department of Obstetrics-Gynecology, District Hospital, Warsaw, Poland

325

After many years of experimental studies weobtained permission in 1988 from the ResearchEthical Committee of the Medical Academy inWarsaw to perform a series of therapeutictransplantations of human foetal mesencephalictissue into the brains of patients with Parkinson’sdisease (PD). We followed NECTAR ethicalguidelines for the use of foetal material fortransplantation purposes.

Implantations of human foetal dopaminergiccells taken from the ventral part of one mesen-cephalon of 11-12 week-old foetuses into thehead of the caudate nucleus were performed inthree PD patients aged 48, 53, and 50 years,respectively. All patients had been sufferingfrom the severe form of PD for about 10-15years (stage 4/5 according to Hoehn & Yahrscale) with bradykinesia, rigidity and tremor asthe main symptoms. Long-lasting L-dopa ther-apy resulted in side effects with "ON-OFF"syndrome and dyskinesias.

The operations were performed according toMadrazo’s microsurgical technique. Implanta-tion of foetal tissue into the caput of the caudatenucleus was carried out by means of an instru-ment devised by Zabek. One day before theoperation immunosuppressive therapy wasintroduced and continued for 6 postoperativemonths. A detailed clinical examination wasperformed before and every 3 months after theoperation according to the battery of inter-national tests recommended by CAPIT.

The patients were under post-operationalobservation lasting 30, 20 and 12 months,respectively. Improvement was observed in allpatients starting between 3 and 6 months afteroperation until the present. Significant increasesin movement speed for repeated pronation-supination, finger dexterity and foot lifting tests

were found. The speed of walking also increasedwith decreased rigidity. The "OFF" phase duringthe day became shorter and less severe; dys-kinesias were markedly reduced. Some of theresults obtained during the 30-month recovery ofpatient No. 1 are presented in the followingFigure and Table.

It seems that the 30 and 20 months recoveryof patients No. 1 and No. 2, respectively, is along enough term of observation to recommendthe benefits of intracerebral transplantations inhopeless patients, who have already exhaustedall the other therapeutic possibilities and areconscious that the course of the disease willslowly progress and deteriorate. In all patientsrecovery was not observed before 3 months aftertransplantation. Probably, this period of time isnecessary for sprouting and creation of aneuronal network between the graft and the hostbrain. The improvement increased between the3rd and 6th months, was still continuing duringthe following months and reached a stable stageat 9-12 months after the transplantation.

Despite the fact that the doses of L-dopacould not be decreased we observed that theduration of dyskinesias and OFF phase de-creased significantly in all cases. It is also worthnoting that despite the unilateral DA cell im-plantation, bilateral motor improvement wasfound. Our results indicate that foetal graftingseems to be a valuable method for selectedparkinsonian patients. However, we shouldnever forget that at present neural transplanta-tion is still an experimental approach.

(C) FREUND PUBLISHING HOUSE LTD., LONDON. JOURNAL OFNEURALTRANSPLANTATION & PLASTICYrY,Vol. 3, No. 4,1992

Page 2: 30-Month ResultsofFoetal Cell into the Brains of ...downloads.hindawi.com/journals/np/1992/721764.pdf · Pronationsupination Fingerdexterity EFFECT "OFF"phase duringtheday(%) Durationof

326

TF_,STS OF MOVEMENTABILI’IW

3’1POSTOPERATIVE OBSERVATION (months)

Foot lifting

Pronationsupination

Finger dexterity

EFFECT

"OFF" phaseduring the day (%)

Duration ofdyskinesiasduring the day (%)

BEFORETRANSPLAN-

TATION

55

18

48

MONTHS AFTER TRANSPLANTATION

3 6 9 18 24 27

30 20 17 18 18 18

30

18

16 15 12 10 11 11 10 10

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