Sci­en­tists try 1st gene edit­ing in­side body of Oak­land pa­tient

Manteca Bulletin - - Local -

OAK­LAND (AP) — Sci­en­tists for the first time have tried edit­ing a gene in­side the body in a bold at­tempt to per­ma­nently change a per­son’s DNA to try to cure a dis­ease.

The ex­per­i­ment was done Mon­day in Cal­i­for­nia on 44-year-old Brian Madeux. Through an IV, he re­ceived bil­lions of copies of a cor­rec­tive gene and a ge­netic tool to cut his DNA in a pre­cise spot.

“It’s kind of hum­bling” to be the first to test this, said Madeux, who has a meta­bolic dis­ease called Hunter syn­drome. “I’m will­ing to take that risk. Hope­fully it will help me and other peo­ple.”

Signs of whether it’s work­ing may come in a month; tests will show for sure in three months.

If it’s suc­cess­ful, it could give a ma­jor boost to the fledg­ling field of gene ther­apy . Sci­en­tists have edited peo­ple’s genes be­fore, al­ter­ing cells in the lab that are then re­turned to pa­tients. There also are gene ther­a­pies that don’t in­volve edit­ing DNA.

But th­ese meth­ods can only be used for a few types of dis­eases. Some give re­sults that may not last. Some oth­ers sup­ply a new gene like a spare part, but can’t con­trol where it in­serts in the DNA, pos­si­bly caus­ing a new prob­lem like can­cer.

This time, the gene tin­ker­ing is hap­pen­ing in a pre­cise way in­side the body. It’s like send­ing a mini sur­geon along to place the new gene in ex­actly the right location.

“We cut your DNA, open it up, insert a gene, stitch it back up. In­vis­i­ble mend­ing,” said Dr. Sandy Macrae, pres­i­dent of Sang­amo Ther­a­peu­tics, the Cal­i­for­nia com­pany test­ing this for two meta­bolic dis­eases and he­mo­philia. “It be­comes part of your DNA and is there for the rest of your life.”

That also means there’s no go­ing back, no way to erase any mis­takes the edit­ing might cause.

“You’re re­ally toy­ing with Mother Na­ture” and the risks can’t be fully known, but the stud­ies should move for­ward be­cause th­ese are in­cur­able dis­eases, said one in­de­pen­dent ex­pert, Dr. Eric Topol of the Scripps Trans­la­tional Sci­ence In­sti­tute in San Diego.

Pro­tec­tions are in place to help en­sure safety, and an­i­mal tests were very en­cour­ag­ing, said Dr. Howard Kauf­man, a Bos­ton sci­en­tist on the Na­tional In­sti­tutes of Health panel that ap­proved the stud­ies.

He said gene edit­ing’s prom­ise is too great to ig­nore. “So far there’s been no ev­i­dence that this is go­ing to be dan­ger­ous,” he said. “Now is not the time to get scared.”


Fewer than 10,000 peo­ple world­wide have th­ese meta­bolic dis­eases, partly be­cause many die very young. Those with Madeux’s con­di­tion, Hunter syn­drome , lack a gene that makes an en­zyme that breaks down cer­tain car­bo­hy­drates. Th­ese build up in cells and cause havoc through­out the body.

Pa­tients may have fre­quent colds and ear in­fec­tions, dis­torted fa­cial fea­tures, hear­ing loss, heart prob­lems, breath­ing trou­ble, skin and eye prob­lems, bone and joint flaws, bowel is­sues and brain and think­ing prob­lems.

“Many are in wheel­chairs ... de­pen­dent on their par­ents un­til they die,” said Dr. Ch­ester Whit­ley, a Univer­sity of Min­nesota ge­net­ics ex­pert who plans to en­roll pa­tients in the stud­ies.

Weekly IV doses of the miss­ing en­zyme can ease some symp­toms, but cost $100,000 to $400,000 a year and don’t pre­vent brain dam­age.

Madeux, who now lives near Phoenix, is en­gaged to a nurse, Mar­cie Humphrey, who he met 15 years ago in a study that tested this en­zyme ther­apy at UCSF Be­nioff Chil­dren’s Hospi­tal Oak­land, where the gene edit­ing ex­per­i­ment took place.

He has had 26 oper­a­tions for her­nias, bunions, bones pinch­ing his spinal col­umn, and ear, eye and gall blad­der prob­lems.

“It seems like I had a surgery every other year of my life” and many pro­ce­dures in be­tween, he said. Last year he nearly died from a bron­chi­tis and pneu­mo­nia at­tack. The dis­ease had warped his air­way, and “I was drown­ing in my se­cre­tions, I couldn’t cough it out.”

Madeux has a chef’s de­gree and was part owner of two restau­rants in Utah, cook­ing for US ski teams and celebri­ties, but now can’t work in a kitchen or ride horses as he used to.

Gene edit­ing won’t fix dam­age he’s al­ready suf­fered, but he hopes it will stop the need for weekly en­zyme treat­ments.

Ini­tial stud­ies will in­volve up to 30 adults to test safety, but the ul­ti­mate goal is to treat chil­dren very young, be­fore much dam­age oc­curs.


A gene-edit­ing tool called CRISPR has got­ten a lot of re­cent at­ten­tion, but this study used a dif­fer­ent one called zinc fin­ger nu­cle­ases. They’re like molec­u­lar scis­sors that seek and cut a spe­cific piece of DNA.

The ther­apy has three parts: The new gene and two zinc fin­ger pro­teins. DNA in­struc­tions for each part are placed in a virus that’s been al­tered to not cause in­fec­tion but to ferry them into cells. Bil­lions of copies of th­ese are given through a vein.

They travel to the liver, where cells use the in­struc­tions to make the zinc fin­gers and prepare the cor­rec­tive gene. The fin­gers cut the DNA, al­low­ing the new gene to slip in. The new gene then di­rects the cell to make the en­zyme the pa­tient lacked.

Only 1 per­cent of liver cells would have to be cor­rected to suc­cess­fully treat the dis­ease, said Madeux’s physi­cian and study leader, Dr. Paul Har­matz at the Oak­land hospi­tal.

“How bul­let­proof is the tech­nol­ogy? We’re just learn­ing,” but safety tests have been very good, said Dr. Carl June, a Univer­sity of Penn­syl­va­nia sci­en­tist who has done other gene ther­apy work but was not in­volved in this study.


Safety is­sues plagued some ear­lier gene ther­a­pies. One worry is that the virus might pro­voke an im­mune sys­tem at­tack. In 1999, 18-year-old Jesse Gelsinger died in a gene ther­apy study from that prob­lem, but the new stud­ies use a dif­fer­ent virus that’s proved much safer in other ex­per­i­ments.

An­other worry is that in­sert­ing a new gene might have un­fore­seen ef­fects on other genes. That hap­pened years ago, when re­searchers used gene ther­apy to cure some cases of the im­mune sys­tem dis­or­der called “bub­ble boy” dis­ease. Sev­eral pa­tients later de­vel­oped leukemia be­cause the new gene in­serted into a place in the na­tive DNA where it un­in­ten­tion­ally ac­ti­vated a can­cer gene.

“When you stick a chunk of DNA in ran­domly, some­times it works well, some­times it does noth­ing and some­times it causes harm,” said Hank Greely, a Stan­ford Univer­sity bioethi­cist. “The ad­van­tage with gene edit­ing is you can put the gene in where you want it.”

Fi­nally, some fear that the virus could get into other places like the heart, or eggs and sperm where it could af­fect fu­ture gen­er­a­tions. Doc­tors say built-in ge­netic safe­guards pre­vent the ther­apy from work­ing any­where but the liver, like a seed that only ger­mi­nates in cer­tain con­di­tions.

This ex­per­i­ment is not con­nected to other, more con­tro­ver­sial work be­ing de­bated to try to edit genes in hu­man em­bryos to pre­vent dis­eases be­fore birth — changes that would be passed down from gen­er­a­tion to gen­er­a­tion.

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