Cherisse Moe

For peo­ple with sick­le cell dis­ease, life is of­ten de­fined by a re­lent­less cy­cle of pain crises, hos­pi­tal ad­mis­sions and ma­jor or­gan com­pli­ca­tions.

Now, re­searchers are test­ing treat­ments that tar­get the bi­ol­o­gy be­hind the ill­ness, rais­ing the pos­si­bil­i­ty of chang­ing how it af­fects pa­tients. One of the lat­est is renizgam­glo­gene au­to­gedtem­cel, known as reni-cel, an ex­per­i­men­tal gene-edit­ing ther­a­py test­ed in the RU­BY tri­al. Re­search pub­lished in the New Eng­land Jour­nal of Med­i­cine found that 27 of 28 pa­tients had no va­so-oc­clu­sive events af­ter re­ceiv­ing the ther­a­py. These episodes oc­cur when sick­led red blood cells block blood flow, caus­ing pain and po­ten­tial­ly con­tribut­ing to or­gan dam­age. Reni-cel al­so pro­duced sub­stan­tial in­creas­es in haemo­glo­bin and foetal haemo­glo­bin. The find­ings are en­cour­ag­ing, but the treat­ment re­mains in­ves­ti­ga­tion­al, with the tri­al car­ry­ing a me­di­an fol­low-up of 9.5 months.

Speak­ing to Guardian Me­dia, con­sul­tant haema­tol­o­gist and med­ical di­rec­tor of the Na­tion­al Blood Trans­fu­sion Ser­vice, Dr Shiv­ir Moo­sai said the sig­nif­i­cance of the de­vel­op­ment must be viewed against the dam­age the ill­ness can cause over time. “Al­though sick­le cell dis­ease is pri­mar­i­ly a dis­or­der af­fect­ing the haemo­glo­bin in red blood cells, it ex­tends far be­yond. The ab­nor­mal red blood cells can block small blood ves­sels and are bro­ken down pre­ma­ture­ly, caus­ing anaemia. Years of re­peat­ed episodes can pro­gres­sive­ly dam­age or­gans such as the brain, lungs, liv­er, kid­neys, bones and eyes. Pa­tients may de­vel­op se­vere in­fec­tions, strokes and chron­ic pain, and it is this cu­mu­la­tive dam­age, rather than pain crises alone, that can short­en life ex­pectan­cy.”

That heavy glob­al toll is un­der­scored by da­ta from the World Health Or­gan­i­sa­tion, which es­ti­mates 7.74 mil­lion peo­ple were liv­ing with the con­di­tion in 2021, with near­ly 80 per cent of cas­es in sub-Sa­ha­ran Africa and 376,000 deaths world­wide that year.

Un­der­stand­ing the sci­ence

“Sick­le cell dis­ease is an in­her­it­ed dis­or­der caused by a ge­net­ic mu­ta­tion,” Moo­sai ex­plained, break­ing down the un­der­ly­ing sci­ence. Un­like tra­di­tion­al gene ther­a­pies, reni-cel does not cor­rect that un­der­ly­ing mu­ta­tion. In­stead, us­ing CRISPR-Cas12a tech­nol­o­gy, it dis­rupts BCL11A bind­ing sites in the reg­u­la­to­ry re­gions of the HBG1 and HBG2 pro­mot­ers to re­ac­ti­vate foetal haemo­glo­bin pro­duc­tion—high­er lev­els of which pre­vent red blood cells from sick­ling.

While the ge­net­ic mu­ta­tion re­mains present, ex­perts de­scribe the ther­a­py’s suc­cess as a func­tion­al cure be­cause it sup­press­es the cel­lu­lar sick­ling process, halt­ing down­stream com­pli­ca­tions. “Al­though the re­sults are very en­cour­ag­ing, the num­ber of pa­tients is rel­a­tive­ly small and longer fol­low-up is need­ed be­fore we know how durable the ben­e­fit will be.”

An in­side look

The metic­u­lous process be­gins with a pa­tient’s own blood-form­ing stem cells.

“Us­ing ad­vanced tech­nol­o­gy in a lab set­ting, the DNA of those stem cells is edit­ed to switch foetal haemo­glo­bin pro­duc­tion back on,” Moo­sai said, “pro­tect­ing the red blood cells from sick­ling and pre­vent­ing fu­ture crises.”

This is not a sim­ple in­jec­tion. It re­quires hos­pi­tal­i­sa­tion and high-dose chemother­a­py to clear space in the bone mar­row. Sig­nif­i­cant short-term side ef­fects in­clude se­vere in­fec­tions, low blood counts and in­fer­til­i­ty. “There are al­so un­cer­tain­ties about very long-term ef­fects of gene edit­ing, which is why pa­tients re­quire pro­longed mon­i­tor­ing,” he added.

Oth­er gene ther­a­pies are al­ready ap­proved in­ter­na­tion­al­ly, pro­vid­ing en­cour­ag­ing ev­i­dence that this ap­proach can of­fer last­ing ben­e­fits. One such treat­ment is Cas­gevy, which us­es CRISPR-Cas9. It was ap­proved in the Unit­ed States in 2023 and, on Ju­ly 1, 2026, the US Food and Drug Ad­min­is­tra­tion ex­pand­ed its use to el­i­gi­ble pa­tients aged two years and old­er with sick­le cell dis­ease and re­cur­rent va­so-oc­clu­sive crises.

The pos­si­ble ben­e­fits

For some­one who has lived with the dis­ease since child­hood, the po­ten­tial im­pact is enor­mous. If the re­sults prove durable, pa­tients could ex­pe­ri­ence a bet­ter qual­i­ty of life and less de­pen­dence on on­go­ing treat­ments. As Moo­sai said: “It could al­low peo­ple to at­tend school, work, trav­el and plan their lives with much less fear of the next cri­sis. How­ev­er, dam­age to or­gans that oc­curred be­fore treat­ment may not nec­es­sar­i­ly be re­versed.”

For now, stan­dard man­age­ment ap­proach­es re­main vi­tal. The oral med­ica­tion hy­drox­yurea helps the body pro­duce more foetal haemo­glo­bin to keep red blood cells from dis­tort­ing in­to sick­le shapes, while blood trans­fu­sions of­fer re­lief for se­vere anaemia. Pa­tients al­so re­ly on rou­tine vac­ci­na­tions, in­fec­tion-fight­ing an­tibi­otics, and folic acid, paired with reg­u­lar mon­i­tor­ing and co­or­di­nat­ed care.

Along­side these tra­di­tion­al ther­a­pies, he not­ed that care­ful donor se­lec­tion and ad­vances in trans­plant tech­niques have im­proved out­comes con­sid­er­ably, es­tab­lish­ing trans­plan­ta­tion as a cru­cial op­tion for el­i­gi­ble pa­tients.

Clos­er to home

Ac­cord­ing to the doc­tor, re­li­able na­tion­al sta­tis­tics are not avail­able, though pub­lished new­born screen­ing da­ta from To­ba­go in­di­cates sick­le cell dis­ease af­fects ap­prox­i­mate­ly one in 176 births, with the sick­le cell trait present in about nine per cent of births. Bring­ing such ad­vanced op­tions to the twin-is­land na­tion would re­quire sig­nif­i­cant health-sys­tem trans­for­ma­tion, with costs be­ing a ma­jor chal­lenge.

“First, the treat­ment would need to com­plete clin­i­cal de­vel­op­ment and re­ceive the ap­pro­pri­ate reg­u­la­to­ry ap­provals,” he said. “Trinidad and To­ba­go would then need to con­sid­er fund­ing and de­vel­op or ac­cess the high­ly com­plex in­fra­struc­ture re­quired for stem cell col­lec­tion, gene ma­nip­u­la­tion, stem cell trans­plan­ta­tion and long-term fol­low-up. Cost will be a ma­jor con­sid­er­a­tion. In prac­ti­cal terms, this would re­quire co­or­di­nat­ed plan­ning in­volv­ing haema­tol­o­gists, trans­plant cen­tres, lab­o­ra­to­ries, re­gion­al health au­thor­i­ties and po­ten­tial­ly in­ter­na­tion­al treat­ment cen­tres.”

With those clin­i­cal ques­tions still open, pa­tients and med­ical teams await the ex­tend­ed fol­low-up da­ta need­ed to con­firm long-term dura­bil­i­ty—and whether these break­through op­tions can suc­cess­ful­ly tran­si­tion from tri­als in­to ac­ces­si­ble re­gion­al care.