Luis Pereira de Almeida

Title

Gene ther­a­py: His­tor­i­cal con­text, chal­lenges, and break­throughs — the GeneT initiative

Abstract

Gene ther­a­py stands as the cul­mi­na­tion of over 150 years of sci­en­tif­ic progress, trac­ing its roots to the foun­da­tion­al work of Gre­gor Mendel and Charles Dar­win. This rev­o­lu­tion­ary approach to treat­ing genet­ic dis­or­ders rep­re­sents the con­ver­gence of genet­ics, mol­e­c­u­lar biol­o­gy, and med­i­cine, embody­ing the relent­less pur­suit of under­stand­ing and manip­u­lat­ing the fun­da­men­tal build­ing blocks of life.

The jour­ney from Mendel’s pea plants to today’s cut­ting-edge gene edit­ing tech­niques has been marked by both remark­able achieve­ments and sig­nif­i­cant chal­lenges. Recent years have wit­nessed tremen­dous advance­ments in gene ther­a­py tools, includ­ing the refine­ment of viral and non-viral vec­tors. How­ev­er, the path to clin­i­cal suc­cess has been com­plex, with obsta­cles rang­ing from vec­tor effi­ca­cy and safe­ty con­cerns to insuf­fi­cient knowl­edge of dis­ease mech­a­nisms and a lack of reli­able mod­els and bio­mark­ers. Despite these hur­dles, the land­scape of gene ther­a­py is rapid­ly evolv­ing. Break­throughs in iden­ti­fy­ing causative gene muta­tions and com­mon dis­ease mech­a­nisms are open­ing new ther­a­peu­tic avenues. The advent of gene edit­ing tech­nolo­gies and induced pluripo­tent stem cells has rev­o­lu­tion­ized our abil­i­ty to cre­ate more accu­rate dis­ease mod­els and devel­op nov­el cell sources for regen­er­a­tive medicine.

Exam­ples of work on polyg­lu­t­a­mine Macha­do-Joseph dis­ease exem­pli­fy the poten­tial of gene ther­a­py in address­ing brain dis­or­ders. Over two decades, we have devel­oped promis­ing tech­nolo­gies encom­pass­ing gene replace­ment, gene silenc­ing, gene edit­ing, and stem cell trans­plan­ta­tion. These approach­es not only offer hope for this spe­cif­ic con­di­tion but also serve as a mod­el for tack­ling oth­er neu­ro­log­i­cal diseases.

With hun­dreds of ther­a­peu­tic strate­gies in devel­op­ment and more than 20 approved prod­ucts, gene ther­a­py is poised to trans­form the treat­ment of mono­genic dis­eases and can­cer. How­ev­er, high prices severe­ly lim­it equi­table access to patients world­wide. Approved prod­ucts have been with­drawn or promis­ing pro­grams dis­con­tin­ued due to lack of reim­burse­ment by health­care sys­tems or insuf­fi­cient com­mer­cial inter­est. To rem­e­dy these short­com­ings, ini­tia­tives are under­way to guar­an­tee uni­ver­sal access and find sus­tain­able, finan­cial­ly accept­able alter­na­tive models.

The ongo­ing imple­men­ta­tion of GeneT – Gene Ther­a­py Cen­ter of Excel­lence (Por­tu­gal), rep­re­sents a sig­nif­i­cant step for­ward in address­ing these chal­lenges. This ini­tia­tive con­nect exper­tise across nation­al bor­ders to tack­le bot­tle­necks in clin­i­cal trans­la­tion, man­u­fac­tur­ing scal­a­bil­i­ty, and reg­u­la­to­ry path­ways. By fos­ter­ing col­lab­o­ra­tion across bor­ders, it aims at extract­ing the full poten­tial of gene ther­a­py in address­ing unmet med­ical needs while strength­en­ing Europe’s lead­er­ship in this trans­for­ma­tive field.

This sem­i­nar will explore the cur­rent state of gene ther­a­py, high­light­ing both its suc­cess­es and ongo­ing chal­lenges. By exam­in­ing its his­tor­i­cal con­text and recent break­throughs along­side the imple­men­ta­tion of GeneT – Gene Ther­a­py Cen­ter of Excel­lence Por­tu­gal, we aim to fos­ter dis­cus­sions on over­com­ing remain­ing bar­ri­ers to ensure equi­table access to life-chang­ing ther­a­pies worldwide.

Biog­ra­phy

Luís Pereira de Almei­da is a Group Leader and Coor­di­nates CNC – Cen­ter for Neu­ro­science and Cell Biol­o­gy and the Cen­ter for Inno­v­a­tive Bio­med­i­cine and Biotech­nol­o­gy – Asso­ciate Lab­o­ra­to­ry (CIBB) at the Uni­ver­si­ty of Coim­bra, since 2020. He is Asso­ciate Pro­fes­sor at the Fac­ul­ty of Phar­ma­cy. He has been work­ing in the field of gene ther­a­py since 1998, when he con­duct­ed his doc­tor­al stud­ies at the Gene Ther­a­py Cen­ter in Lau­sanne CHUV, Switzer­land, focus­ing on brain dis­eases such as Macha­do-Joseph disease.

He is a mem­ber of the Sci­en­tif­ic Advi­so­ry Board of the Angel­man Syn­drome Alliance, the CTGCT Inter­na­tion­al Advi­so­ry Board, and Adamas­tor Bioser­vices. He also serves on the Strate­gic Coun­cil of the Asso­ci­at­ed Lab­o­ra­to­ries Coun­cil. Through­out his career, he has led over 40 projects, includ­ing GeneT – a Team­ing project under the Hori­zon Europe pro­gram aimed at estab­lish­ing a new Gene Ther­a­py Cen­ter of Excellence.

Link to the insti­tu­tion­al web­page: https://cibb.uc.pt/pt/people/l‑almeida