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.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Scripps reach­es $10M set­tle­ment with gov­ern­ment over al­le­ga­tions NIH grants weren't prop­er­ly ac­count­ed for

Scripps Research Institute has settled a case with the Justice Department alleging claims of misappropriated funds, the US attorney for the district of Maryland announced late last week.

Prosecutors said the institute improperly used NIH-funded research grants for non-grant related activities, including working on new grant applications, teaching activities and other administrative tasks. As part of the settlement, Scripps has agreed to pay $10 million.

Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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