Ophumelele kwiNgxoxo kaMongameli: IMbasa yeNgxoxo kaDavid Marsden | iNgqungquthela ka-2026

Ndiyakuhalalisela, Vincenzo, kwaye ndiyabulela ngethuba lokuthetha nawe kwakhona.

UNjingalwazi Vincenzo Bonifati: Enkosi kakhulu, Tiago. Kuluvuyo olukhulu ukuthetha nawe nokuxoxa ngale mbasa.

UNjingalwazi Tiago Outeiro: Sithethe kunyaka ophelileyo [00:01:00] kwiCongress. Ndonwabele ukuba nodliwanondlebe nawe, ngoko ke ndiyazi kancinci ngemvelaphi yakho, kodwa mhlawumbi singathetha ngakumbi ngomsebenzi wakho kunye nento ekuzise kule mbeko intle yeSociety. Kwaye ndiyazi ukuba ufumene iimbeko ezininzi, kuquka neMbasa yeNkonzo eDumileyo ye-MDS President kunye nezinye iimbasa ezinkulu zamazwe ngamazwe.

Ngoko ke ndifuna ukuqala ngokubuza, ezi ngqwalasela ziyichaphazela njani ikhondo lakho lomsebenzi kunye neenethiwekhi zakho kunye nendlela oqhagamshelana ngayo noogxa bakho kwaye mhlawumbi uqale neeprojekthi ezintsha?

UNjingalwazi Vincenzo Bonifati: Okokuqala, mandithi eli lilungelo elikhulu kum ukufumana eli Mbasa leMarsden. Ndicinga ukuba kuye wonke umntu onolwazi ngezifo zengqondo okanye umphandi weengxaki zokunyakaza, eli liphupha elizalisekayo lokufumana eli mbasa, ngoko ke ndizukile kakhulu kwaye ndonwabile kakhulu ngalo.

Ukufumana imbeko kwiintlanganiso zamazwe ngamazwe kulungile kwinethiwekhi yakho, ewe, ngakumbi kubantu [00:02:00] abenza uphando olufana nokufumana ii-genes. Lo ngumdlalo obandakanya intsebenziswano eninzi. Enyanisweni, ngokulungiselela intetho yaseMarsden, bendihlaziya iinethiwekhi zam zentsebenziswano, kwaye ndibale ukuba ndicinga ukuba kukho amakhonkco angaphezu kwe-100 ahlukeneyo namaziko ahlukeneyo kumazwekazi amane, kwaye akunakwenzeka ukuba uwadwelise onke kwisilayidi.

Ngoko ke olu hlobo lophando luxhomekeke kakhulu kwintsebenziswano eninzi noogqirha ababalaseleyo, ingakumbi, abachaza iintsapho esisebenza kuzo. Kulukhuthazo olukhulu ukuqatshelwa ngophando lwakho kuba abanye abantu baya kunxibelelana nathi baze bazame ukuseka amakhonkco ongezelelweyo.

Kodwa ngaphandle kwamabhaso, kwimeko yam, ukufunyanwa kokuqala okubalulekileyo okwakuyi-DJ-1 gene, ukuya kuthi ga ngo-2003, kwaba lukhuthazo olukhulu kumsebenzi wam, kwinethiwekhi yam. Emva kwaloo ncwadi, eyapapashwa kwi-[00:03:00] Science , bekukho inani labantu ababefuna ukusebenzisana nokuthumela iisampulu kunye nokuthumela iintsapho kum.

Ngoko ke ndicinga ukuba mhlawumbi eyona nto ibalulekileyo ekwakheni uthungelwano oluphumelelayo kukuba namaphepha abalulekileyo kunye nokwenza iintetho ezibalulekileyo kwiingqungquthela. Kodwa ke, ewe, ukuqatshelwa ngamabhaso. Ngokuqinisekileyo.

UNjingalwazi Tiago Outeiro: Ngoku siza kubuyela kwisayensi yakho kungekudala, kodwa ndifuna ukubuyela emva ndixelele abaphulaphuli bethu indlela owaqala ngayo ukungena kweli candelo. Ngoko ke waqeqeshwa njengengcali yezifo zengqondo eRome, waza wangena kwi-human molecular genetics e-Erasmus MC eRotterdam, apho unguprofesa khona. Ngoko ke ungasihambisa kuhambo lwakho kwaye yintoni eyakutsalayo kwi-clinical neurology ukuya kwi-genetics?

UProfesa Vincenzo Bonifati: Ewe. Ndafunda ubugqirha ndaza ndaphumelela eRoma, e-Itali, ndaza ndafumana nesatifikethi sam kwi-neurology yeklinikhi apho ndaza ndaqala ukusebenza njengengcali ye-neurologist kwiYunivesithi yaseRoma, ndixakekile kukuxilongwa kunye nonyango, ingakumbi kwi-Parkinson's disease [00:04:00]. Kwakhona nezinye iingxaki zokunyakaza, kodwa ngakumbi i-PD.

Emva koko ngexesha lomsebenzi wam wezonyango, ndaqonda ukuba zininzi izigulane ezine-PD ezixela imbali entle yosapho, nto leyo ngelo xesha, kwaye sithetha ngayo kwiminyaka engama-35 eyadlulayo, yayingaqatshelwa. Babembalwa abantu ababefuna ngokwenene iintsapho ezinesifo sikaParkinson.

Iincwadi zezifundo ze-neurology zazisithi i-PD ayiqhelekanga, ayisiyomfuza, akukho mbali yosapho. Enyanisweni, imbali yosapho yayithathwa njengeyona ndlela yokungabandakanywa ekuxilongweni kwe-PD. Ngoko ke, kuloo meko, ndachukumiseka kakhulu kukuba mhlawumbi omnye kwabane kwizigulane wayenembali yosapho yesi sifo, ndaza ndaqala ukukhangela... ukuhlola ezo zihlobo. Ngemoto yam, ndihambahamba nemoto yam ngeempelaveki, kwiilali ezijikeleze iRoma ukuze ndibone abo bantu kuba babengenakuza eyunivesithi kwaye kwakungekho zibonelelo zophando zokwenza loo nto ngelo xesha.

Kwakufana nje nento yokuzonwabisa. Kwaye [00:05:00] emva koko inyathelo ngenyathelo, ndaqokelela iintsapho ezininzi, ezandizisa kwiintlanganiso, zindibonisa iipowusta malunga neentsapho ezinezifo zikaParkinson ezivela e-Itali, kwaye oko kwavuselela umdla wabanye abantu bamazwe ngamazwe ababesenza into efanayo. Oku kwandenza ndadibana no-Anita Harding, owayenguvulindlela kwi-neurogenetics, njengoko wayesakha iqela laseYurophu kwi-genetics ye-PD phakathi kweminyaka yoo-90.

Yayilulo olo qalo lwam, masithi, kuhlobo lophando olukumgangatho wehlabathi kwi-genetics. Kwiminyaka embalwa kamva, umdla wam kwi-genetics wawunamandla kangangokuba ndandifuna ukufudukela kwilebhu ukuze ndijoyine enye inxalenye yentsebenziswano. Ngoko ke ndingena kuphando lweempawu zonyango, kuphando lwe-DNA yezo ntsapho, yiyo loo nto ndafudukela eNetherlands kwaye umsebenzi wam watshintsha, ndaza ndahlala apho ukususela ngoko.

Ndahlala apha. Andizange ndibuyele ekliniki kwakhona.

UNjingalwazi Tiago Outeiro: Ngoko ke kufuneka ukuba ubunabacebisi abaninzi endleleni. Ngaba kukho amagama ofuna ukuwakhankanya [00:06:00] kwaye mhlawumbi usixelele ukuba ayila njani indlela ocinga ngayo ngeengxaki zokunyakaza namhlanje?

UProfesa Vincenzo Bonifati: ERoma, umcebisi wam yayinguGiuseppe Meco, owayenguprofesa we-neurology ojongene nekliniki kaParkinson. Wandifundisa iinkalo zonyango zokuxilonga kunye nonyango lwe-PD. Kwaye wayengumcebisi olungileyo kakhulu kwiinkalo ze-neuropsychiatric ze-neurology, ezibaluleke kakhulu.

Ngelishwa, wasweleka kwiminyaka embalwa eyadlulayo ngaphambi kwexesha, ngewayenokonwaba kakhulu ukuba aye kwiNtetho yam yaseMarsden kule mihla. Kodwa ke, xa ndafudukela eNetherlands, ndafumana abacebisi ababini ababalulekileyo, ingakumbi uPeter Huetink. Wayeyintloko yelabhoratri yophando lweengxaki zokunyakaza eRotterdam.

Kwaye mhlawumbi ube ngumcebisi obalulekileyo kum ngokwesayensi. Wandazisa kwimigaqo yophando lwemfuza yomntu, ingakumbi uhlalutyo lonxibelelwano, indlela yokwahlula ikhowudi yemfuza kwiintsapho ezinkulu, nto leyo eyaba negalelo elikhulu ekufumaneni izinto ezinkulu [00:07:00] kwiminyaka engama-20 edlulileyo kwimfuza.

Kwakhona, emva kokuba uPeter efudukele eAmsterdam, uBen Oostra, owayengunjingalwazi opheleleyo kwicandelo lethu. Wayekwangumcebisi wam wokugqibela emsebenzini wam. Ndaza ndaba ngunjingalwazi oncedisayo ndaza ndaba ngunjingalwazi opheleleyo kwilebhu kaBen Oostra. Emva kokuthatha umhlala-phantsi ngoku ndingoyena mdala kwiqela lophando.

UNjingalwazi Tiago Outeiro: Ngumsebenzi omangalisayo kwaye ukhankanye amagama amakhulu, ngoko ke ndiqinisekile ukuba bekumnandi kakhulu kwaye kuyakhuthaza ukusebenza nabo bonke abo basebenzi.

UProfesa Vincenzo Bonifati: UPeter Huetink ngumntu owayengumbhali ophezulu wokufunyanwa kwe-tau gene, umzekelo, njengesizathu se-frontotemporal dementia njengenye yeempumelelo zakhe. I-tau gene yafunyanwa ngenene ngelixa ndandisele ndisebenzisana noPeter wase-Itali njengogqirha wezifo zengqondo. Kwaye uBen Oostra nguyise we-Fragile X gene, enye yezona zinto zokuqala zifunyenweyo kwi-molecular genetics. Ndandikwindawo entle kakhulu, [00:08:00] indawo ekhuthazayo.

UNjingalwazi Tiago Outeiro: Ewe. Ngokucacileyo, oko kukuncedile ukuba ufezekise zonke izinto ezinkulu ozifumeneyo. Ngoko ke ndingathanda ukukhankanya kafutshane ezo zinto ndikubuze ukuba ungathi zeziphi izinto ezibalulekileyo ozifumeneyo kwi-genetics kule minyaka idlulileyo?

Sele ukhankanyile nge-DJ-1, kodwa andazi ukuba ufuna ukugqamisa ezinye na.

UProfesa Vincenzo Bonifati: Ndicinga ukuba uDJ-1 wayengumntu wokuqala owafumana amanqaku amaninzi, kodwa indima yam apho yayiyeyomntu oselula. Ndandingumntu ophandayo kwiqela, njengomntu olingana nomfundi wePhD. Ndifumene uDJ-1 ngezandla zam, kodwa yayiyeyona ndima intsha, indima yomntu oselula.

Kwiminyaka embalwa kamva, esinye isiphumo esibalulekileyo esafika kanye xa ilebhu yam sele imiselwe, ngoko ke kum njenge-PI ephambili, yayikukufunyanwa kwesifo sokuthutha i-manganese esibangelwe kukuguquka kwe-gene ye-solute carrier, i-SLC30A10, eyayithathwa njenge-zinc transporter ngelo xesha.

Kwaye sayichonga njengeyona [00:09:00] ithwala i-manganese eyintloko emntwini. Eso yayingesosisombululo sesifo esingaqhelekanga kuphela kodwa yayikukuqala kwesahluko esitsha kwezonyango, i-metabolism ye-manganese emntwini. Kwaye ngoku siyazi ukuba kukho ubuncinane iiproteni ezintathu, ezibhalwe ziijini ezahlukeneyo, ezidlala indima eyahlukileyo ekuthuthweni kwe-manganese kwizitho ezahlukeneyo emzimbeni.

Lo ngumzekelo omhle wamandla okufumanisa kwi-physiology yomntu yolu hlobo lungaqhelekanga lwe-genetics. Ngoko ke ufumana unobangela wesifo somntu, isifo esingaqhelekanga kwiimeko ezininzi, kwaye mhlawumbi nendlela yonyango kwabo baguli. Kodwa kwangaxeshanye, ukhanyisa i-physiology yomntu.

Kwaye le ngxaki yokuthuthwa kwe-manganese ngumzekelo omhle kakhulu waloo nto. Ngoko ke ndiyazingca kakhulu ngaloo nto ifunyenweyo.

Kwiminyaka kamva, enye endiyithanda kakhulu kukufumana i-gene ye-generalized dystonia form, eyi-EIF2AK2. Yi-kinase ye-[00:10:00] eukaryotic initiation factor 2 alpha, eyi-protein ebalulekileyo yempendulo yoxinzelelo oludibeneyo emntwini.

Bekukho amacebiso amaninzi sele ekho okuba i-dystonia inxulumene nokuphendula koxinzelelo olungasebenzi kakuhle, kodwa oku kufunyanisiweyo kwabeka omnye wabadlali abaphambili kwindlela njengesizathu se-dystonia eqhelekileyo yabantu. Ngoko ke kuqinisekisa le ngcamango yokuba i-dystonia, ubuncinane ezinye zeendlela eziqhelekileyo zokuqala kwangethuba, mhlawumbi ukuba uyathanda, iindlela ezimbi ngokwezonyango, ziyindlela yokubonakalisa impendulo etshintshileyo kuxinzelelo kwiiseli.

Oku, ngokombono wam, kunefuthe elibalulekileyo nakwiphuhliso lonyango olunokwenzeka lwesi sifo. Kwaye iijini ezininzi, kuquka i-DYT1, i-DYT6, kwane-sarcoglycan dystonia, zichaphazela le ndlela ngandlela thile. Kodwa ijini yethu, leyo siyifumene kwilebhu yam, iphakathi kakhulu kwindlela. Ngoko ke ngokombono wam, oku kukwanegalelo elibalulekileyo ngokwesayensi.

Bekukho ezinye izinto ezifunyenweyo [00:11:00], ewe, zezinye iijini. Nganye kuzo isenokuba ityhila enye into ye-mosaic yesifo sikaParkinson okanye i-dystonia. Ngoku sisebenza kwenye into entle kakhulu kwisifo sikaParkinson. Yijini entsha, engekashicilelwa, kwaye eneneni ndiceba ukuthetha kancinci ngale nto ekupheleni kweMarsden Lecture. Elo lijini endicinga ukuba liza kuba nomdla kakhulu ngeziphumo zalo kwi-pathogenesis ye-PD kunye nokuxhaphaka kwabantu.

UProfesa Tiago Outeiro: Ndiyawuthanda kakhulu umsebenzi wakho kuba awugcini nje ngokwenza izifundo ezimangalisayo kwimfuza yomntu kodwa ungena nakwiindlela ezisetyenziswa ngayo, kwaye umsebenzi wakho uzise ulwazi olutsha ngeendlela ezisetyenziswa ngayo izifo. Ngoko ke, oko kubaluleke kakhulu ukuze sizame ngenye imini ukunyanga ezi zifo ngcono kunento esiyenzayo namhlanje.

Ngoko ke oko kuyamangalisa kakhulu.

UProfesa Vincenzo Bonifati: Enkosi kakhulu. Enyanisweni ewe, yinjongo yethu leyo, ukufumana unyango.

UNjingalwazi Tiago Outeiro: Ngoku, ndishiya umbono opheleleyo [00:12:00] ngokusekelwe kumava akho kubaphulaphuli abancinci. Ungabacebisa ngantoni abaphandi abancinci abazama ukungena kwicandelo leengxaki zokunyakaza kwaye mhlawumbi nemfuza yomntu? Ngaba ikho ingcebiso onokubanika yona malunga nendlela abafanele bayibumbe ngayo imisebenzi yabo?

UNjingalwazi Vincenzo Bonifati: Ndicinga ukuba ikamva liqaqambile ngokwenene kwi-genetics. Ngoko ke okokuqala, umyalezo wam kubantu abaselula kukuba ukuba bafuna ukungena kuphando kwi-genetics yeengxaki zokuhamba kusengcono kakhulu ukwenza njalo kwaye ndiqinisekile ukuba kuya kubakho ezinye izinto ezininzi eziza kufunyanwa kwi-genetics.

Ngoko ke ngokuqinisekileyo licandelo apho umphandi oselula anokutyala imali kulo. Kodwa ke kukho nezinye. Into ebalulekileyo kum kumsebenzi wam, ndicinga, zizinto ezintathu. Into enye kukuba neengcinga ezilungileyo, ukubona into mhlawumbi phambi kwabanye enokuba yinto ebalulekileyo kwaye usebenzele kuyo.

Ukusebenza nzima kakhulu [00:13:00]. Kufuneka usebenze nzima kakhulu kuba kunzima, ukufumana izinto ezibalulekileyo kunzima. Kucacile ukuba kunzima. Ngoko ke kufuneka uchithe ixesha elininzi kwaye uzingise, phantse ucinge ngento ethile, ukuze ufumane iziphumo ezibalulekileyo ngokwenene.

Kwaye kufuneka ube nethamsanqa elincinci, ndicinga. Oko kubalulekile ebomini kuba ndiyazazi iingcali zemfuza ezininzi ezingakhange zifumane ii-genes ezininzi kwaye nazo zinjalo... ngamanye amaxesha kubalulekile ukuba ube ngexesha elifanelekileyo, ngexesha elifanelekileyo, kwindawo efanayo, ukuze ube nonxibelelwano oluhle noogqirha, kunye neelabhoratri.

Njengoko ndiza kuthetha kwintetho, yonke into efunyenweyo ngokwemfuza, ubuncinane kum, ibali lahlukile kwaye linencasa eyahlukileyo. Ngamanye amaxesha kukusebenzisana nogqirha okhethekileyo, ngamanye amaxesha nososayensi okhethekileyo. Ngoko ke kufuneka ukwazi ukuguquguquka, masithi, nakwimisebenzi yakho.

 Ubuncinane oku koko, kwi [00:14:00] umbono wam, kube sisitshixo sempumelelo yam kuphando.

Mhlawumbi umyalezo omnye obalulekileyo endifuna ukuwudlulisela kwisizukulwana esitsha kukuba kufuneka ube nomonde. Kufuneka usebenze ixesha elide. Iprojekthi ebalulekileyo ayisiyoprojekthi yenyanga, yeenyanga ezintandathu. Inokuhlala iminyaka.

Ukufumana i-DJ-1 kundithathe iminyaka emibini ndisebenza, kwaye akukho mntu wayenokuqinisekisa kwasekuqaleni ukuba ndiza kufumana i-gene. Isenokuba yayikukusilela ngokupheleleyo, akunjalo? Ngoko ke kufuneka usebenze kwaye ube nomdla ngomsebenzi wakho ngaphandle kokudimazeka kukusilela kunye nenyaniso yokuba kufuneka uphinde uvavanyo izihlandlo ezininzi. Ndicinga ukuba kwihlabathi langoku ngokusasazeka kwe-intanethi kunye neendaba ufumana umbono wempumelelo ovela lula kwiinkalo ezahlukeneyo zehlabathi.

Yonke into iyenzeka, kwaye kubonakala ngathi, ewe, nam ndingenza into ethile kwaye iza kusebenza kwaye iza kuphumelela. Kodwa ngelishwa, inyani ayinjalo.

UNjingalwazi Tiago Outeiro: Thina [00:15:00] siyazi ukuba isayensi ayinjalo.

UNjingalwazi Vincenzo Bonifati: Xa sasingabafundi bePhD kwakungekho intanethi, ngoko ke yayiyimbono eyahlukileyo ngokupheleleyo yendlela eya empumelelweni, akunjalo?

Mhlawumbi namhlanje yonke into iyandiswa, yonke into iyakhawuleziswa, kwaye oku kunokukhokelela ekungaqondini kakuhle ukuba kulula ukuba njani ekupheleni kweprojekthi eyimpumelelo, akunjalo? Ubuncinane, ndiyayiqonda le nto, lo mceli mngeni namhlanje.

UProfesa Tiago Outeiro: Ewe, kufuneka basebenze nzima baze bahlale beqinile kwaye begxile. Oko kubaluleke kakhulu. Kwaye ngoku, ukuba sijonge phambili, kumbuzo wethu wokugqibela, ukuba sijonge kwiminyaka eli-10 ezayo, ngoko khawucinge ukuba ngoku siku-2036, ucinga ukuba siza kuba phi ngokwemfuza yesifo sikaParkinson?

UNjingalwazi Vincenzo Bonifati: Ngokukodwa kwiParkinson's, kwiminyaka eli-10 ezayo, uninzi ukuba aluyiyo yonke imfuza enxulumene nesi sifo iya kuchongwa. I-GP2 yenza umsebenzi omhle kakhulu wokumisela le nxalenye iseleyo yokufunyanwa ngoyilo lolawulo lweemeko, akunjalo?

Ngoko ke [00:16:00] siqokelela inani elikhulu lamatyala kunye nolawulo, sikhangela naluphi na uhlobo lomahluko, ukusuka kokungaqhelekanga ukuya kokuqhelekileyo, olunokudlala indima kwisifo. Andithandabuzi ukuba konke oku kudweliswa kweenguqu ezinxulumene nesifo kuya kuqondakala ngokupheleleyo. Okwangoku, kwakhona, indlela esekelwe kusapho iya kuqhubeka nokuvelisa iziphumo, kwaye indlela esekelwe kusapho kunye nezifundo zokudibanisa imfuza ziya kuthethana kwaye zichumise indawo yazo yophando.

Kodwa umbuzo uya kuba yindlela yokuguqula ukufunyanwa kwemfuza ibe ziindlela zonyango kunye nokuthintela. Ndicinga ukuba lowo uza kuba ngumbuzo ophambili wophando kwiminyaka eli-10 ezayo. Kwaye ndiyathemba ukuba ngelo xesha siya kuba sele sinobungqina bexabiso lokuguqulela kwezi zinto zifunyenweyo zemfuza.

Sele kukho iimvavanyo ezininzi zeklinikhi eziqhutywa okwangoku ngokusekelwe ekufumaneni i-genetic, nokuba yi-GBA okanye i-synuclein okanye i-LRRK2. Ezo zezona zintathu zibaluleke kakhulu [00:17:00]. Kusenzima ukubonisa impembelelo yokuguqula isifo. Ewe, oko kunzima. Oko kufuna ixesha elininzi kunye nemizamo emininzi. Kodwa kum, akukho mathandabuzo okuba le yindlela eya kwixesha elizayo. Le yindlela engaphambili yokuguqula isifo kwaye ekugqibeleni kuthintelwe isifo. Umbuzo ophambili uya kuba xa kufuneka uzame ukunyanga abantu abachaphazelekayo kuba xa isifo sibonakala ngokwezonyango, kusenokuba sekwephuzile, nokuba umntu ojolise kuye uchanekile, ukuba iyeza lichanekile.

Kusenokuba sekudlule ixesha ukuba kube yinto ebalulekileyo ngokwezonyango. Yiloo nto endiyixhalabeleyo. Ngoko ke uphando malunga nokuxilongwa kwangethuba kunye neempawu zesimo sesifo ngaphambi kokuba sivele, ndicinga ukuba kuya kuba baluleke kakhulu kwiminyaka eli-10 ezayo ukususela ngoku.

UNjingalwazi Tiago Outeiro: Enkosi, Vincenzo. Ngoko ke zininzi izimvo ezibalulekileyo ozishiyileyo kwaye ikwayindlela yokusixelela sonke ukuba siye kumamela intetho yakho kwingqungquthela. Vincenzo, ndifuna ukukubulela kwakhona ngeli thuba, ngokuthetha nathi nokusixelela kancinci [00:18:00] ngomsebenzi wakho kunye nendawo esikuyo namhlanje ngemfuza yomntu kunye nazo zonke izinto ezibalulekileyo ozifumanisileyo.

Enkosi kakhulu, Vincenzo.

UNjingalwazi Vincenzo Bonifati: Enkosi kakhulu, Tiago, kwaye enkosi kubaphulaphuli kwaye siya kubonana nonke kungekudala eSeoul.

UNjingalwazi Tiago Outeiro: Enkosi. Ngoko ke siye sadlan’ udliwanondlebe noNjingalwazi Bonifati ngomhla wokunikezelwa kweMbasa yakhe kaDavid Marsden ngo-2026. Enkosi nonke ngokumamela, kwaye nize nijoyine nathi kwiipodcasts zethu ezizayo. [00:19:00]