Mass cloning for neu­ro re­search? Chi­nese sci­en­tists re­port birth of five gene-edit­ed mon­keys

Re­mem­ber when Chi­nese re­searchers an­nounced the birth of the first mon­keys cre­at­ed by so­mat­ic cell nu­clear trans­fer? Ex­act­ly a year lat­er, the same team is re­port­ing a sec­ond break­through — cloning five gene-edit­ed mon­keys in an ef­fort to over­come pre­vi­ous con­cerns about the costs and ef­fi­cien­cy in us­ing cloned mon­keys for med­ical re­search.

“It can be said that this re­search means the tech­nol­o­gy for cloning gene-edit­ed mon­keys has made the leap from the­o­ry to prac­tice,” sci­en­tists from the Chi­nese Acad­e­my of Sci­ences In­sti­tute of Neu­ro­science in Shang­hai write in a blog­post for Chi­nese me­dia Sina.

Car­ry­ing a ge­net­ic al­ter­ation that pre­dis­pos­es them to dys­reg­u­la­tion of the cir­ca­di­an rhythm, the five mon­keys are ex­pect­ed to shed light on dis­ease mech­a­nisms and of­fer ther­a­peu­tic test­ing ground for neu­rode­gen­er­a­tion. In dis­eases such as Alzheimer’s and Parkin­son’s, mice mod­els have proven woe­ful­ly in­ad­e­quate in terms of pre­dict­ing hu­man re­ac­tions to drugs, cre­at­ing a big hur­dle in pre­clin­i­cal ex­per­i­ments for new ther­a­pies.

Like Zhong Zhong and Hua Hua, the iden­ti­cal long-tailed macaques in the spot­light last Jan­u­ary, the new mon­keys — now three to six months old — were cloned in a process that in­volves tak­ing the nu­cle­us of a dif­fer­en­ti­at­ed cell from one an­i­mal and in­fus­ing it in­to an emp­ty egg cell from an­oth­er. An elec­tric cur­rent trig­gers the egg to de­vel­op in­to an ear­ly em­bryo and the re­sult­ing fe­tus, grown in a sur­ro­gate, would be a repli­ca of the an­i­mal that do­nat­ed the nu­cle­us.

In their case, the donor was an abort­ed mon­key fe­tus. While adult cells were al­so test­ed in a sep­a­rate co­hort of the tri­al, both ba­bies born in that group were short-lived and one had ab­nor­mal body de­vel­op­ment.

This time around, re­searchers think they have cracked the code for “batch pro­duc­ing” iden­ti­cal mon­keys that all pos­sess a de­sired trait, state-owned Xin­hua re­port­ed, cit­ing a pa­per from Chi­nese jour­nal Na­tion­al Sci­ence Re­view. Specif­i­cal­ly, they knocked out BMAL1, a “clock gene” re­spon­si­ble for pro­duc­ing a “clock pro­tein,” in the donor mon­key.

No­tably, the suc­cess rate of cloning is still the same as in ear­li­er ex­per­i­ments at around 1% — a pos­i­tive sign, the sci­en­tists say, con­sid­er­ing the added com­plex­i­ties of us­ing adult cells and tweak­ing DNA.

Re­searchers have ob­served signs of sleep dis­or­ders, anx­i­ety and be­hav­iors in these mon­keys that are sug­ges­tive of schiz­o­phre­nia, they added in the blog­post.

They al­so told Xin­hua that the pro­gram “ad­hered to in­ter­na­tion­al ethics stan­dards and recog­ni­tion,” with sup­port and su­per­vi­sion from the in­sti­tute’s ethics pan­el.

Im­age: Five cloned mon­keys. SCI­ENCE CHI­NA PRESS

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.