National Institutes of Health Rejected Funding for Moir’s Radical Theories

(p. B14) Robert D. Moir, a Harvard scientist whose radical theories of the brain plaques in Alzheimer’s defied conventional views of the disease, but whose research ultimately led to important proposals for how to treat it, died on Friday [December 20, 2019] at a hospice in Milton, Mass. He was 58.

His wife, Julie Alperen, said the cause was glioblastoma, a type of brain cancer.

Dr. Moir, who grew up on a farm in Donnybrook, a small town in Western Australia, had a track record for confounding expectations. He did not learn to read or write until he was nearly 12; Ms. Alperen said he had told her that the teacher at his one-room schoolhouse was “a demented nun.” Yet, she said, he also knew from age 7 that he wanted to be a scientist.

. . .

Conventional wisdom held that beta amyloid accumulation was a central part of the disease, and that clearing the brain of beta amyloid would be a good thing for patients.

Dr. Moir proposed instead that beta amyloid is there for a reason: It is the way the brain defends itself against infections. Beta amyloid, he said, forms a sticky web that can trap microbes. The problem is that sometimes the brain goes overboard producing it, and when that happens the brain is damaged.

The implication is that treatments designed to clear the brain of amyloid could be detrimental. The goal would be to remove some of the sticky substance, but not all of it.

The idea, which Dr. Moir first proposed 12 years ago, was met with skepticism. But he kept at it, producing a string of papers with findings that supported the hypothesis. Increasingly, some of the doubters have been won over, said Rudolph Tanzi, a close friend and fellow Alzheimer’s researcher at Harvard.

Dr. Moir’s unconventional ideas made it difficult for him to get federal grants. Nearly every time he submitted a grant proposal to the National Institutes of Health, Dr. Tanzi said in a phone interview, two out of three reviewers would be enthusiastic, while a third would simply not believe it. The proposal would not be funded.

For the full obituary, see:

Gina Kolata. “Robert Moir, 58, Researcher Who Rethought Alzheimer’s.” The New York Times (Saturday, December 21, 2019): B14.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the obituary was last updated December 23 [sic], 2019, and has the title “Robert Moir, 58, Dies; His Research Changed Views on Alzheimer’s.”)

French Regulations Require Only Doctors Can Identify the Dead

(p. A4) DOUAI, France — Her mother’s death had been expected. Terminally ill with breast cancer, she lay in a medical bed in her living room, visited daily by a nurse.

But when Sandra Lambryczak’s 80-year-old mother died earlier this year, in the predawn hours of a Saturday morning, the daughter suddenly discovered a growing problem in France’s medical system: By law, the body couldn’t be moved until the death was certified by a medical doctor, but a shortage of personnel can sometimes force families to keep their deceased loved ones at home for hours or even days.

. . .

Doctors have resisted pressure from some politicians to delegate the authority to certify deaths to other health care officials. They argue that it is a serious medical procedure and that a mistake in noting the cause of death could have legal consequences.

“There are doctors, if they don’t know the patient well, say to themselves that they don’t want trouble later on,” said Dr. Olivier Bouchy, the vice president of the French Medical Council in the department of Meuse. “Signing a death certificate is not harmless.”

As with many things in France, tradition is perhaps also an obstacle to changing the doctor’s role in certifying deaths. The death certificate process, Dr. Bouchy said, harked back to an earlier time.

. . .

In France, the state’s role in regulating people’s daily lives — including in matters of health — remains strong. So the lack of a doctor, especially at the emotionally vulnerable moment when a family member dies, can feel like a deep betrayal.

“We felt abandoned by the state,” said Frédéric Deleplanque, who had to wait more than two days for a doctor to certify the death of his father-in-law, Jean-Luc Bajeux, a retired autoworker. “We were nothing.”

For the full story, see:

Norimitsu Onishi. “An Agonizing Delay After a Death at Home.” The New York Times (Tuesday, December 17, 2019): A4.

(Note: ellipses added.)

(Note: the online version of the story has the date December 16, 2019, and has the title “In France, Dying at Home Can Mean a Long Wait for a Doctor.”)

ALS Drug Entrepreneurs Developed Idea in Dorm Room and Self-Funded the Early Development

(p. B3) An experimental drug slowed the paralyzing march of amyotrophic lateral sclerosis, or Lou Gehrig’s disease, in a clinical trial, according to researchers who say the results are a fresh sign that recent insights into the condition may soon bring new medicines.

. . .

The idea for the drug came to Amylyx Chief Executive Josh Cohen, he said, while he was a Brown University junior in 2012 and 2013 majoring in biomedical engineering and reading scientific papers on how neurons die.

Mr. Cohen told Mr. Klee, whom he had first met playing club tennis in college. Mr. Klee, a neuroscience major, spent the following night reading up on his friend’s idea.

“We did what most people in our generation do” when trying to learn about a topic, Mr. Klee said. “We went to the Internet. We Googled it.”

The research shed light on some molecular routes that neurodegeneration follows, which Mr. Cohen said sparked his interest in combining drugs that attacked two important pathways. The problem was, each drug alone hadn’t worked in studies.

Unfamiliar with both drug research and the industry, Messrs. Cohen and Klee sounded out experts, including Dr. Cudkowicz, to learn how to test their hypothesis in a laboratory, start a company and conduct testing in patients.

Their project took off after the pair scraped together $6,000 from personal savings and family donations to pay contract researchers in Finland, who found their combination drug worked in a petri dish.

Mr. Cohen took all his courses during his final year of college on Thursdays so he could devote the rest of the week to Amylyx.

Mr. Klee, who had moved to Cambridge, Mass., after graduating, took odd jobs coaching swimming, working as a research technician and participating in medical-research studies to earn money for the fledgling startup then based in his apartment.

The company, based in Cambridge, had three employees last March and seven today, but plans to add 100 employees next year.

For the full story, see:

Jonathan D. Rockoff. “ALS Drug Shows Promise in Study.” The Wall Street Journal (Tuesday, December 17, 2019): B3.

(Note: ellipsis added.)

(Note: the online version of the story has the same date as the print version, and has the title “ALS Drug Works in Study, Researchers Say.” The sentences quoted after the ellipsis above, appear in the online, but not in the print, version of the article.)

Muyembe Had Knowledge of an Ebola Cure Before Clinical Trial

(p. A1) In a medical breakthrough that compares to the use of penicillin for war wounds, two new drugs are saving lives from the virus and helping uncover tools against other deadly infectious diseases. They were proven effective in a gold-standard clinical trial conducted by an international coalition of doctors and researchers in the middle of armed violence.

. . .

(p. A10) Dr. Muyembe set out on his path to an Ebola treatment during the 1995 outbreak. He transferred blood from five survivors to eight patients, hoping that the antibodies that kept some people alive would keep others from dying. Seven of the patients who received the blood transfusion recovered.

He published the results in a scientific journal in 1999. Other researchers said the study was small and had failed to include a control group, a comparison set of patients who weren’t given the treatment, to fully test its efficacy.

For the full story, see:

Betsy McKay. “From a War Zone Came an Unexpected Cure for Ebola.” The Wall Street Journal (Thursday, October 31, 2019): A1 & A10.

(Note: ellipsis added.)

(Note: the online version of the story has the date Oct. 30, 2019, and has the title “‘Ebola Is Now a Disease We Can Treat.’ How a Cure Emerged From a War Zone.”)

Stents Do Not Reduce Heart Attacks or Deaths

(p. A17) The findings of a large federal study on bypass surgeries and stents call into question the medical care provided to tens of thousands of heart disease patients with blocked coronary arteries, scientists reported at the annual meeting of the American Heart Association on Saturday [Nov. 16, 2019].

The new study found that patients who received drug therapy alone did not experience more heart attacks or die more often than those who also received bypass surgery or stents, tiny wire cages used to open narrowed arteries.

That finding held true for patients with several severely blocked coronary arteries. Stenting and bypass procedures, however, did help some patients with intractable chest pain, called angina.

. . .

Stenting costs an average of $25,000 per patient; bypass surgery costs an average of $45,000 in the United States. The nation could save more than $775 million a year by not giving stents to the 31,000 patients who get the devices even though they have no chest pain, Dr. Hochman said.

. . .

But getting a stent does not obviate the need for medical therapy, Dr. Boden noted. Since patients with stents need an additional anti-clotting drug, they actually wind up taking more medication than patients who are treated with drugs alone.

About a third of stent patients develop chest pain again within 30 days to six months and end up with receiving another stent, Dr. Boden added.

For the full story, see:

Kolata, Gina. “Drugs Are Shown to Reduce Need For Surgery to Fix Blocked Arteries.” The New York Times, First Section (Sunday, November 17, 2019): A17.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the story has the date Nov. 16, 2019, and has the title “Surgery for Blocked Arteries Is Often Unwarranted, Researchers Find.” The online version says that the page number of the New York print edition was A19. The page number of my National edition was A17.)

Rapamycin Will Be Tested to Extend Lifespan of Dogs

(p. 1A) SEATTLE (AP) — Can old dogs teach us new tricks? Scientists are looking for 10,000 pets for the largest-ever study of aging in canines. They hope to shed light on human longevity too.

The project will collect a pile of pooch data: vet records, DNA samples, gut microbes and information on food and walks. Five hundred dogs will test a pill that could slow the aging process.

“What we learn will potentially be good for dogs and has great potential to translate to human health,” said project co-director Daniel Promislow of the University of Washington School of Medicine.

. . .

(p. 2A) Dogs weighing at least 40 pounds will be eligible for an experiment with rapamycin, now taken by humans to prevent rejection of transplanted kidneys. The drug has extended lifespan in mice. A small safety study in dogs found no dangerous side effects, said project co-director Matt Kaeberlein of the University of Washington.

For the full story, see:

Carla K. Johnson of The Associated Press. “Needed: 10,000 Dogs for Project That Could Also Benefit Humans.” Omaha World-Herald (Thursday, Nov. 15, 2019): 1A-2A.

(Note: ellipsis added.)

(Note: the online version of the story has the date Nov. 17 [sic], 2019, and has the title “Old dogs, new tricks: 10,000 pets needed for science.”)

“Rejuvenate Bio” Startup Succeeds in Using Gene Therapy to Fight Age-Related Diseases in Mice

The online PNAS article mentioned below includes the information that one of the article’s referees was Aubrey de Grey, Cambridge scientist, and co-author of The End of Aging. Aubrey de Grey has been arguing for many years that anti-aging research will only take-off when proof-of-concept is achieved with mice. The PNAS article summarized below, appears to provide that proof-of-concept.

(p. A13) North Grafton, Mass.

A Cavalier King Charles spaniel named Shadow was at the front lines of a new approach to gene therapy.

Earlier this month, 7-year-old Shadow was the first dog to be screened at Tufts University for a pilot study attempting to use gene therapy to treat a type of heart disease that often afflicts aging cavaliers.

It’s part of a novel approach to gene therapy that has successfully treated age-related ailments in mice. Now it is being studied in dogs, with eventual hopes to test it in humans.

Researchers reported their success in mice in a study published Monday [Nov. 4, 2019] in the journal PNAS. They treated four age-related diseases in mice using genetic therapy: heart and kidney failure, Type 2 diabetes and obesity. On average, the mice experienced a 58% increase in heart function, a 75% reduction in kidney degradation, and normalized weight and blood-sugar levels in mice fed a high-fat diet, the study found.

. . .

What’s interesting about the new research in mice is that it is broader—targeting not a single rare defect, but common age-related ailments. The experiments injected mice with DNA to create an extra copy of a healthy gene, expressing more healthy material in cells linked to common diseases of aging.

The goal of the biotech company behind the mice study, Rejuvenate Bio —which sprang from research out of the lab of Harvard geneticist George Church, who is a co-founder—is to treat multiple aging-related diseases in dogs. It recently started working with Tufts University’s Cummings School of Veterinary Medicine on the dog pilot. If successful in dogs, the company hopes to treat similar human diseases but says that will take a lot more resources and time.

The firm says it expects the cost of dog genetic therapies would be similar to dog cancer treatments, including surgery, which range from about $500 to $8,000.

. . .

Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York City, praised the PNAS study as a proof of concept . . .

For the full story, see:

Sumathi Reddy. “YOUR HEALTH; Gene Therapy Targets Aging.” The Wall Street Journal (Tuesday, Nov. 4, 2019): A13.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the story has the date Nov. 4, 2019, and has the title “YOUR HEALTH; A New Approach to Gene Therapy—Now In Dogs, Maybe Later In Humans.”)

The PNAS article, summarized in the passages quoted above, is:

Davidsohn, Noah, Matthew Pezzone, Andyna Vernet, Amanda Graveline, Daniel Oliver, Shimyn Slomovic, Sukanya Punthambaker, Xiaoming Sun, Ronglih Liao, Joseph V. Bonventre, and George M. Church. “A Single Combination Gene Therapy Treats Multiple Age-Related Diseases.” Proceedings of the National Academy of Sciences (PNAS) (Nov. 4, 2019): https://doi.org/10.1073/pnas.1910073116.

The book co-authored by Aubrey de Grey, and mentioned way above, is:

de Grey, Aubrey, and Michael Rae. Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. New York: St. Martin’s Press, 2007.