TIEP CAN MOI TRONG DIEU TRI BENH PARKINSON

II^NHiN nn TH€ G161

TIEP CAN MOI TRONG DIEU TRI BENH PARKINSON

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Benh Parkinson diTqfc James Parkinson m6 t^ lan dau ti6n vao ddu th6' ky XIX nhif la chufng liet rung r6l lo^n thin kinh phd big'n nhdt. Gdn ddy, nhiTng phat hl0n v6^ di truy§n va t§' bao hoc dugfc xem la mOt trong nhufng kd't qui quan trQng nhdt trong didu trj cdn benh dang gia tdng nhanh chong nay.

T

heo sd lidu cOa Lidn hpp qudc, trdn thd gidi cd ft nhdt 4 tridu ngUdi mdc bdnh Parkinson. Con sd nay se tang gdp ddi khi sd ngudi sap gid tren thd gidi khdng ngUng tang len. Vdi khodng 50% sd benh nhdn mdc benh sau 60 tudi vd 50%

trudc 60 tudi nen ddy khdng ch? Id benh cua ngudi gid. Cdc chuyen gia cung cdnh bao, chUng rdi logn ndy cdn cd the tan cdng cd ngudi dudi 40 tudi.

TU thd ky XIX, benh Parkinson da dupc bidt d i n nhu nhOng rdi loan van dpng ciJa cd the: bdn tay, canh tay run ray; chan, tay cUng nhac;

van dpng chdm chap; suy yeu vd thang bang vd phdi hdp. Ngodi ra, mpt sd benh nhan gap khd khan trong di lai, ndi nang, ngu, tieu tien.. NhQng rdi loan vd suy yeu ndy bat ngudn tU sU chdt cua cdc npron ( t l bdo than kinh). Mac du ndron cd mat d trong todn bp nao nhung chf nhQng ndron dopamin mdi bj tdn thUPng. Cdc ndron sdn sinh dopamin ndy Id thdnh phdn chu yd'u cua cdc hgch than kinh thupc mpt sd dd phUc tgp nam sdu ben trong nao didu chfnh su chfnh xdc vd phdi hdp trong vdn dpng.

Ban dau, nao vdn cd thd hogt ddng binh thudng du bj mat cdc npron sinh dopamin d liem den. Nhung khi mdt niia sd te bdo chuyen hda nay mat di, sp thilu hut se khiln cho cdc phan cua nao khdng cdn Id mdt ddn vj thd'ng nhat vd phdi hpp nhu trude, cu thd Id khdng tham gia k i l m sodt dUde sU van ddng eua ddi thj, hgch cd bdn vd vo nao. Khi dd mdi bieu hien ra ben ngodi cdc trieu chUng cua benh.

Cac bieu hien huy hoai cua protein

Khi nghidn cUu vai trd cua protein, cdc nhd khoa hpc da phdt hidn ra mdi lidn kd't giUa cdc protein sai hdng vd bdnh Parkinson. NhQng phat hidn ndy da cijng cd nidm tin cho cdc phuong phap d i l u trj mdi.

Trong nhieu ca mdc bdnh Parkinson, sp huy hogi cd thd thd'y rd khi d nhQng bui protein bdn trong cac npron sinh dopamin d lidm den.

NhOng bui protein nhu vay cdn gap d nhQng ngUdi mac benh Alzheimer (chUng mat tri nhd) vd Huntington (rdi loan cdm xuc vd suy sup tinh than) nhung trong trUdng hpp benh Parkinson, cac bui nay dupe gpi la the Lewy (lay ten cua nha bdnh hpc ngudi DUc phat hien ra chung lan dau tien). Cdc nhd khoa hpc chuyen nghien cUu benh Parkinson da tranh ludn soi ndi vd vd'n dd lidu bdn thdn cdc bui protein g§y nen su hijy hogi hay Id giQ vai trd logi bd cdc phdn tii ddc ra khdi cac ndron?

Tuy nhidn, cdc quan d i l m ndu ra ddu thdng nhd't d mdt d i l m chung Id vide tim h i i u nhQng bui protein Id chia khda d l hieu dupe bdnh Parkinson.

Khi protein dupe tgo thdnh, cdc phdn tii chaperon gd'p chung thdnh dgng 3 c h i l u vd cdc chaperon ndy cdn gd'p khue Igi cdc protein dd bj dudi ra trudc dd. N l u cdc protein khdng dupc gd'p khue thfch hpp trong lan thU nhd't, hodc khdng dupc gd'p khue Igi chfnh xdc d lan sau dd thi chung se bj logi bd bdi he thdng ubiquitin proteasom. Trude het, mpt protein nhd gpi Id ubiquitin

gdn vdo protein bidn dgng. Cdc ubiquitin dUpc gdn tidp cho tdi khi chudi ubiquitin che trdn protein bj hu hdng. Cdc chudi ndy bdo ddng cho proteasom ciJa t l bdo thdn kinh vd sp cd mat cua protein dupc danh ddu. Sau dd proteasom phdn gidi protein nay thdnh cdc axit amin.

Nhidu nhd khoa hpc cho rdng, bdnh Parkinson xud't hidn khi cac h§ thdng chaperon vd ubiquitin proteasom hogt ddng sai. Hp Idp ludn rdng, Ccic npron cua chdt xam bj mpt tdn thupng ndo dd dd gdy ra mdt chudi stress te bdo, ddn den hang logt protein gap khue sai tap hpp Igi. Ban dau, vide tap hdp nay cd the ddng vai trd bdo ve, vi cac protein hu hdng k i t hpp vdi nhau se cdn trd tinh trgng rdi logn ben trong td bdo. Sau dd, cdc chaperon se gd'p khue Igi vd hd thdng don rdc bdt ddu logi bd cdc protein ndo khdng cdn khd n§ng trdn. Khi vide tgo thdnh cdc protein gdp khue sai vupt khd nSng, he thdng ubiquitin proteasom bj kim ham, cdc chaperon bj suy kidt vd cac protein bj hiJy hogi tfch luy, sau do Id tinh trgng c h i t xdy ra ddi vdi cac npron.

Gid thuylt ndu tren dUpc nhidu ngudi ddng tinh vi cd t h i gidi thicti cho cd 2 dgng benh Parkinson phd b i i n : Khodng 95% sd benh nhan bi binh do ket qud cua sd tddng tac gida cdc gen vd mdi trddng. Khi m6t ngudi mang gen di truyin gap m6t s d y l u td mdi trudng bd't ldi (nhucac chat trU sinh vdt hgi...) thi cdc t l bao d liem den chju n h i l u stress hdn va tfch luy nhieu protein gd'p khue sai hdn so vdi cung cdc t l bdo d ngUdi

68 K H O A H O C s^'*^^"9 3.2012

NHlN nn TH€ G161

Nao thudng (trii)

vi nao bdnh nhin Parkinson (phii)

khdc. 5% sdbinh nhdn cdn lai mdc binh hodn todn bdi di truyin.

Cac nghien cuu va kha nang ap dung trong dieu tn benh

Cac nha khoa hpc da de xuat cdc phUPng phap dieu trj nham gidm nhe cdc trieu chUng vd tinh trgng thodi hda ndron gdy tien trien benh. Cdc thudc kieu chaperon se dupc phat trien nham kim ham sp phdt tridn cija benh, hoac lieu phdp gen kfch thfch vide tao thdnh cdc chaperon can thilt giup cho viec didu tri gen nham kfch thfch viec tgo thdnh cdc chaperon can thid't.

Ngodi viec theo dudi nhQng dQ lieu mdi lien quan dd'n protein va di truyen, cdc nhd nghien cUu cdn de cap d i n y l u to dinh dudng ndo.

Day Id cdc chat thuc day qud trinh sinh trudng vd phan hda td bdo than kinh. Cdc y l u td ndy khdng chi giup gidm nhe cdc tridu chUng md cdn cd thd bdo ve cdc ndron khdi bj hu hgi hoac thdm chf phuc hdi cdc npron da bj hu hgi.

Mdt hudng khdc bUdc dau dupc thU nghiem tren ddng vat cho thay, mpt logi protein gpi ten la y l u td dinh dudng ndo bat ngudn tU ddng te bdo than kinh dem (GDNF) cd the ldm tdng sU sdng sdt cija cdc ndron sinh dopamin bj hijy hogi vd lam gidm ddng k l cdc tripu chUng cua Parkinson. Cdc phdu thuat vien thude Benh vidn Frenchay (Anh) d& tap trung nghien cUu trong phdng thf nghidm de curig cd'p GDNF cho cdc benh nhan mac bdnh Parkinson. Hp lap mdt dng thdng (catheter) vdo cdc thd van

(corpus striatum) ben trai va ben phdi Id cac vi tri nhan chu yeu trong cac hach cd bdn tiet ra dopamin bdi cac nPron d liem den. Sau do, nhQng the tfch nhd cua GDNF lien tpc dupc truydn vao nao tU mpt bom lap vao bpng. Bom duy tri diJ GDNF trong mpt thang va sau dd dupc tiep tpc bd sung bdng each tiem qua da. Kdt qud ban dau cho thay, cdc trieu chUng da nhp hdn vd cd sp phpc hdi nhdt djnh trong vide hap thu dopamin trong the vSn va d liem den. Tuy this nghiem lam sang tren benh nhan d quy md Idn hPn cho kdt qud chUa thuc sp thuyet phpc nhUng hien day vdn dupc coi Id hudng chij yeu dupc dp dung trong dieu trj.

Mpt sd nghien cUu khac lai ap dpng lieu phap dieu tri gen thay the cho phdu thuat cung cap GDNF, hy vpng gen dUdc chuyen giao se cung cap lau dai lupng GDNF.

Nghien cUu da dupc tien hanh d khi bj nhilm benh, stf dung lentivirut mang gen dpc ma cho GDNF de chuyen giao yeu td nay cho cdc td bao the van sinh ra dopamine vd k i t qua dat dupc rat kha quan:

nhQng khd khan trong van dpng cua kh? gidm dang ke va chung khdng bj tdc dpng bdi viec tiem MPTP mpt hda chat dpc ddi vdi cac ndron tiet dopamin d liem den. DUa vdo nhQng nghien cUu ndy, mpt sd nhd khoa hpc sU dpng ky thuat tUdng tu de chuydn giao protein neurturin cung trong hp GDNF vd thU nghiem mdt gen tUdng tp vdi gen dpc ma neurturin d ngudi.

Cdn Michael Kaplit (Dai hpc Cornell, My) dung gen de kiem sodt mpt sd vung cua ndo hoat ddng qud mgnh khi dopamin dUdc tid't tu liem den gidm manh. Dopamin suy gidm khiln eho cdc ndron sdn sinh glutamat, mdt chat kfch thfch dan truydn than kinh, hogt dpng khdng cd su ddi khdng, tU dd se kfch thfch manh cdc cd quan dfch gay ra nhQng rdi logn hoat dpng.

Kaplit da thuc hien viec thij' nghiem

tren cd the ngudi benh: dng "nhd"

mpt virut chuyen gen dpc ma cho decacboxilaza cua axit glutamic (la loai enzym quan trpng ddi vdi viec tao thanh chdt ddn truyen than kinh kim ham axit gamma amino butiric GABA) vao cac vj trf nay vdi hy vpng, GABA se giup Uc che cac td bao qua kfch thfch va do dd, lam dju nhOng rdi loan vSn ddng Parkinson.

Vdi mpt dng nhd bang spi tdc dUdc xau qua mpt Id tren dfnh hop sp cija benh nhan giup chuydn mpt lUdng nhd virut mang cac ban sao ciia gen den cac ndron cua hach dUdi ddi. Hda chat giai phdng tU cac te bao bj thay ddi khong chf lam dju cac ndron qua hoat dpng ma cdn tac dpng den cac vung nao khac qua hoat dpng...

Cay ghep te bao thay the cdc te bao da chdt hien la phUdng phap dieu tri gay nhieu tranh luan. Ngudi ta cay dUdi da cac te bao cudng phoi hay cac te bao gdc trudng thanh va ddn du cac te bao chua phan hda nay trd thdnh cdc ndron sinh dopamin. Cdc td bao gdc phdi thai bat ngudn tU cdc phdi gid dupc tao thanh trong sU thu tinh in vitro nen viec sU dung chung cdn gay nhidu tranh cai. Mac du da cd nhQng tien bp rd ret trong xac djnh tfn hieu phan tU vd cac bien phap thuc day td bdo de tao thdnh dopamin, nhUng viec cay ghep loai td bao gdc nao Id cd ldi thi chua xdc djnh dupc. Cho tdi nay, cdc thU nghiem lam sdng deu dUde tidn hdnh vdi vat lieu phdi. Cac thCf nghiem da chUng minh rang, hang tram nghin td bdo sinh dopamin cd'y ghep sdng sdt trong cdc cd the ngudi benh, tuy nhien, nhQng ldi feh ve chUc nang cdn rat han chd va mau thudn, chua ke vide dieu tri thudng bdc Id nhQng tdc hai nhu rdi logn van dpng (dau quan qugi, mat kiem sodt va xoan van) •

Nguyin Dinh Quyen (tdng hap)

So thanq 3.2012

Hoatdong

T . T ' T T / ' ^ A T T y - x y i 69