Health
In Alzheimer’s breakthrough, researchers identify ‘protective gene’ that delays disease in high-risk family
A significant Alzheimer’s study is shedding new light on a protective gene that appears to delay the disease in those destined to develop it.
Researchers from two Mass General Brigham hospitals — Mass Eye and Ear and Massachusetts General Hospital — have been studying a large extended family in Colombia with multiple members who have the Paisa mutation, which predicts an extremely high genetic risk of developing early-onset Alzheimer’s disease.
Most people with the Paisa variant develop mild cognitive impairment in their 40s, develop dementia in their 50s and die from complications of dementia in their 60s, according to a press release.
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Among more than 1,000 high-risk family members, 27 of them who have one copy of a rare gene variant — the APOE3 gene, known as Christchurch — reported a delayed onset of symptoms.
A significant Alzheimer’s study sheds new light on a protective gene that appears to delay the disease in those destined to develop it. (iStock)
On average, they developed signs of Alzheimer’s five years later than those who did not have the variant, the researchers found.
By comparison, the drugs currently available for Alzheimer’s slow the disease’s progression by only around six months.
The study findings, published Wednesday in The New England Journal of Medicine, could have important implications for drug development.
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This is a follow-up to a 2019 study in which a woman from the same family who had two copies of the protective APOE3 Christchurch variant did not experience any disease symptoms until her 70s — decades later than the average age of onset, 44.
Joseph F. Arboleda-Velasquez, M.D., PhD, an associate scientist at Mass Eye and Ear who worked on the study, is originally from Colombia, where he spent years studying that woman’s case as part of his medical training.
Imaging scans showed reduced signs of tau and amyloid plaques, the proteins that build up in the brains of Alzheimer’s patients. (iStock)
“It really took the world by storm, the Colombian woman who beat Alzheimer’s — it was an amazing discovery,” he told Fox News Digital.
“But also, we had to be very careful. Was it really true? Could it be reproduced? It would be amazing if we could develop treatments that replicate the effect of the Christchurch variant, but we didn’t have enough evidence.”
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“So, back then, we started this very extensive project of trying to find more individuals who also had Christchurch to see if they were also protected.”
In this latest study, researchers analyzed 1,077 descendants of the Colombian family, narrowing the focus to the 27 people who carried both the Paisa mutation and one copy of the protective Christchurch variant.
“This could really transform lives — not just of the individual, but at the population level.”
On average, these 27 family members began showing signs of cognitive impairment at age 52 — compared to age 47 for those without the Christchurch variant.
For two of the individuals, imaging scans showed reduced signs of tau and amyloid plaques, the proteins that build up in the brains of Alzheimer’s patients, the press release stated.
While the original woman might have been dismissed as a “one-time wonder,” said Arboleda-Velasquez, this new study provides more evidence that could help support building a drug development program.
A doctor points out evidence of Alzheimer’s disease on PET scans at the Center for Alzheimer Research and Treatment at Brigham And Women’s Hospital in Boston, Massachusetts. (REUTERS/Brian Snyder/File Photo)
“Now, instead of one person, we have 27 more men and women — some who work, some who are retired, some in rural areas, some in the city — who all have the Christchurch variant and are all protected,” he said.
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“And now we can move forward with trying to develop therapies that do exactly the same thing.”
He added, “This could really transform lives — not just of the individual, but at the population level.”
The study did have some limitations, the researchers acknowledged.
It analyzed a relatively small number of people carrying both the Paisa and Christchurch variants, all belonging to a single (albeit large) family.
Researchers from two Mass General Brigham hospitals — Mass Eye and Ear and Massachusetts General Hospital — led the new study. (iStock)
Additional studies including larger, more diverse groups are needed to confirm the variant’s protective effect and determine the targets of potential treatments, researchers said.
Some experimental therapies are already being developed, Arboleda-Velasquez noted.
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“A lot of people were very intrigued by the initial Christchurch finding [in 2019], and now this is different,” he said.
“This is a call to action — a call to make drugs that can leverage this discovery.”
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A new drug has been approved for the treatment of schizophrenia in adults.
On Thursday, the U.S. Food and Drug Administration (FDA) approved COBENFY (xanomeline and trospium chloride), an oral medication that is manufactured by Bristol Myers Squibb in New Jersey.
This marks the first new class of medications for the brain disorder in several decades, according to a press release.
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COBENFY is expected to be available in the U.S. in late October, the company noted.
A new drug has been approved for the treatment of schizophrenia in adults. (iStock)
“Today’s landmark approval of our first-in-class treatment for schizophrenia marks an important milestone for the community, where after more than 30 years, there is now an entirely new pharmacological approach for schizophrenia — one that has the potential to change the treatment paradigm,” said Chris Boerner, PhD, board chair and chief executive officer at Bristol Myers Squibb, in the press release.
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Schizophrenia is a serious mental illness that affects a person’s thoughts, feelings and behaviors.
It often causes hallucinations, delusions, disordered speech and loss of touch with reality, Mayo Clinic states on its website.
COBENFY (xanomeline and trospium chloride) is an oral medication that is manufactured by Bristol Myers Squibb in New Jersey. (Bristol Myers Squibb)
The disorder can also lead to lack of emotional expression, lack of motivation, cognitive dysfunction and social withdrawal.
Approximately 2.8 million people in the U.S. and 24 million people globally are living with schizophrenia.
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The disorder has traditionally been treated with antipsychotic medications, but around 40% of patients do not respond to treatments and 60% experience “inadequate improvement” in symptoms or “intolerable side effects,” studies have shown.
COBENFY is expected to be available in the U.S. in late October, the company noted. (Bristol Myers Squibb)
COBENFY works differently than the currently available schizophrenia medications.
“Due to its heterogeneous nature, schizophrenia is not a one-size-fits-all condition, and people often find themselves in a cycle of discontinuing and switching therapies,” said Rishi Kakar, MD, chief scientific officer and medical director at Segal Trials and investigator in the drug’s clinical trials, in the release.
“Schizophrenia is not a one-size-fits-all condition, and people often find themselves in a cycle of discontinuing and switching therapies.”
“The approval of COBENFY is a transformative moment in the treatment of schizophrenia because, historically, medicines approved to treat schizophrenia have relied on the same primary pathways in the brain.”
“By leveraging a novel pathway, COBENFY offers a new option to manage this challenging condition.”
“Today’s landmark approval of our first-in-class treatment for schizophrenia marks an important milestone for the community,” said Chris Boerner, PhD, board chair and chief executive officer at Bristol Myers Squibb. (iStock)
Sam Clark, founder and CEO at Terran Biosciences — a biotech company that develops treatments and technologies for neurological and psychiatric diseases in New York City — commented on the new approval in a statement sent to Fox News Digital.
“I am excited that the FDA has just approved [COBENFY] as a treatment for patients with schizophrenia, marking a big leap forward in the psychiatry space,” he said.
“These patients live with a difficult disease, and this drug with a novel mechanism of action will surely make a significant impact,” Clark continued.
“We look forward to seeing the renaissance continue as this approval paves the way for future breakthroughs and novel patient-focused therapeutics.”
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The approval follows three phases of clinical trials in which COBENFY was shown to result in a “statistically significant improvement in illness.”
Schizophrenia is a serious mental illness that affects a person’s thoughts, feelings and behaviors and often causes hallucinations and delusions. (iStock)
In terms of safety, the medication’s most common side effects during clinical trials were nausea, indigestion, vomiting, diarrhea, constipation, hypertension, abdominal pain, accelerated heart rate, dizziness and gastroesophageal reflux disease, the release stated.
Patients with certain existing medical conditions may experience other, more serious risks.
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People should discuss potential complications with a doctor before starting the medication.
Fox News Digital reached out to Bristol Myers Squibb and the Schizophrenia & Psychosis Action Alliance requesting comment.
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