Ghazaleh Sadri-Vakili. Mass General Research Institute via Twitter

Mass Gen­er­al team presents mouse da­ta to back the case for us­ing re­for­mu­lat­ed asth­ma drug to treat ALS

Can a re­for­mu­la­tion of an old drug on the mar­ket for asth­ma, al­ler­gy and mas­to­cy­to­sis pro­tect against liv­er dis­ease, Alzheimer’s, and amy­otroph­ic lat­er­al scle­ro­sis?

A team from Mass­a­chu­setts Gen­er­al Hos­pi­tal is mak­ing a case for the lat­ter two. Hav­ing re­cent­ly found an in­jec­tion of cro­molyn sodi­um ef­fec­tive in in­hibit­ing amy­loid be­ta (Aβ) ag­gre­ga­tion in vit­ro and in mouse mod­els, re­searchers set out to in­ves­ti­gate whether the same com­pound can achieve the same in ALS.

Their con­clu­sion, pub­lished on Na­ture’s open ac­cess jour­nal Sci­en­tif­ic Re­ports:

Our re­sults in­di­cate that cro­molyn sodi­um treat­ment sig­nif­i­cant­ly de­layed the on­set of neu­ro­log­i­cal symp­toms, and im­proved deficits in PaGE per­for­mance in both male and fe­male mice, how­ev­er, there was on­ly an ef­fect on sur­vival in fe­male mice.

While the pre­cise eti­ol­o­gy of ALS re­mains poor­ly un­der­stood, one the­o­ry pro­pos­es that neu­roin­flam­ma­to­ry process­es are im­pli­cat­ed in its ini­ti­a­tion and pro­gres­sion.

As cro­molyn in­hibits mast cell de­gran­u­la­tion, the sci­en­tists at Mass Gen­er­al hy­poth­e­sized that it could con­vert im­mune cells in the brain, in­clud­ing mi­croglia and as­tro­cytes, from a pro-in­flam­ma­to­ry to an an­ti-in­flam­ma­to­ry state as well as re­duc­ing the lev­els of cy­tokines and chemokines.

Af­ter com­par­ing the ef­fects of once-dai­ly in­jec­tions of cro­molyn ver­sus a place­bo in wild type mice and mice car­ry­ing a ge­net­ic mu­ta­tion for ALS, re­spec­tive­ly, the re­searchers came up emp­ty on the mi­croglia and as­tro­cytes the­o­ry. But they did find low­er lev­els of pro-in­flam­ma­to­ry cy­tokines/chemokines in the spinal cord and plas­ma — in ad­di­tion to ob­serv­ing that the trans­genic mice treat­ed with cro­molyn sodi­um had the high­est mo­tor neu­ron counts among the four groups.

“Our study sup­ports the no­tion that in­flam­ma­tion has a sig­nif­i­cant role in the pro­gres­sion of ALS and there­fore ex­plor­ing an­ti-in­flam­ma­to­ry treat­ments may be of great val­ue for de­vel­op­ing an ef­fec­tive treat­ment,” said Ghaz­a­leh Sadri-Vak­ili, lead au­thor of the study and di­rec­tor of the Neu­roEpi­ge­net­ics Lab­o­ra­to­ry at Mass Gen­er­al, in a state­ment.

Sadri-Vak­ili has pre­vi­ous­ly not­ed that the neu­rol­o­gy de­part­ment at Mass Gen­er­al has a plan in place to get the drug — pro­vid­ed by AZTher­a­pies — in­to the clin­ic for ALS.

Un­like the for­mu­la­tions of cro­molyn cur­rent­ly avail­able through pre­scrip­tion and over the counter, which are ab­sorbed through lung and nasal in­hala­tion or in­gest­ed drops, the ver­sion in­ject­ed in­to mice in the study can be “ful­ly avail­able in the blood­stream” and cere­brospinal flu­id, ac­cord­ing to the biotech.

AZTher­a­pies is con­duct­ing a Phase III tri­al of an­oth­er for­mu­la­tion of cro­molyn, com­bined with oral ibupro­fen, to treat ear­ly Alzheimer’s. It is un­clear whether any clin­i­cal pro­grams are in place to test cro­molyn sodi­um in pri­ma­ry scle­ros­ing cholan­gi­tis af­ter Bay­lor Scott and White Health re­searchers re­port­ed it de­creased bil­iary pro­lif­er­a­tion and fi­bro­sis in mice.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

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CSL CEO Paul McKenzie (L) and CMO Bill Mezzanotte

Q&A: New­ly-mint­ed CSL chief ex­ec­u­tive Paul McKen­zie and chief med­ical of­fi­cer Bill Mez­zan­otte

Paul McKenzie took over as CEO of Australian pharma giant CSL this month, following in the footsteps of long-time CSL vet Paul Perreault.

With an eye on mRNA, and quickly commercializing its new, $3.5 million-per-shot gene therapy for hemophilia B, McKenzie and chief medical officer Bill Mezzanotte answered some questions from Endpoints News this afternoon about where McKenzie is going to take the company and what advances may be coming to market from CSL’s pipeline. Below is a lightly edited transcript.

Boehringer re­ports ro­bust sales led by type 2 di­a­betes and pul­monary drugs, promis­es more to come high­light­ing obe­si­ty

Boehringer Ingelheim reported human pharma sales of €18.5 billion on Wednesday, led by type 2 diabetes and heart failure drug Jardiance and pulmonary fibrosis med Ofev. Jardiance sales reached €5.8 billion, growing 39% year over year, while Ofev took in €3.2 billion, notching its own 20.6% annual jump.

However, Boehringer is also looking ahead with its pipeline, estimating “In the next seven years the company expects about 20 regulatory approvals in human pharma.”

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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FDA ap­proves Nar­can opi­oid over­dose re­ver­sal spray for over-the-counter sale

The FDA today approved Emergent BioSolutions’ Narcan brand naloxone nasal spray for over-the-counter sales. The nod was expected and comes on the heels of a unanimous 19-0 advisory committee vote in favor of approval last month.

The move to OTC means the opioid overdose reversal agent will now be available on grocery, convenience and gas stations shelves, as well as potentially for purchase online.

Michael Foley, Deerfield Discovery and Development CEO

Deer­field Dis­cov­ery nets $50M grant from the state of New York and par­ent com­pa­ny

The discovery arm of the healthcare investment player Deerfield Management Company is getting a major financial boost.

Deerfield Discovery and Development will receive $25 million, over five years, from the state of New York and Empire State Development, a state organization that offers grants, loans and other assistance to companies. Another $25 million will come from Deerfield Management.

The funds will go toward the buildout of a 6,000-square-foot lab space at Cure, a healthcare campus founded by Deerfield at 345 Park Ave. South in New York City. The money will also be used for purchasing equipment and software, operating costs and other items.

J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

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