‘It completely backfired’: The pitfalls of Alzheimer’s genetic testing

CHICAGO, April 21 (Reuters) – Wendy Nelson watched her mom slowly die of Alzheimer’s illness, unable to maneuver or swallow on the finish. “All her pleasures of life had been gone,” Nelson mentioned.

Grief-stricken, petrified of going through the identical dying, Nelson ordered 23andMe(ME.O) DNA take a look at kits for Christmas 2020 for herself and three grownup daughters.

A Boston-based biotech government who’s now 52, Nelson hoped the kits would supply reassurance. They delivered the worst attainable outcome. Nelson has two copies of the APOE4 gene variant that will increase the danger of Alzheimer’s, which implies her threat of creating the illness is eight to 12 occasions greater than folks with the commonest model of APOE.

“It completely backfired,” she mentioned.

Tens of millions of People are anticipated to check for Alzheimer’s within the coming years – some like Nelson, with at-home take a look at kits, others at labs, as new medication for folks with early Alzheimer’s from companions Eisai Co Ltd (4523.T) and Biogen Inc (BIIB.O) and Eli Lilly and Co (LLY.N) usher in sweeping change in approaches to remedy of the illness.

Testing for the APOE4 gene variant amongst People being handled for Alzheimer’s has greater than doubled from a yr in the past, an unique evaluation of medical information for Reuters by well being knowledge agency Truveta discovered. The rise was pushed by the brand new remedies that promise to sluggish the development of the illness, but in addition carry dangers, particularly for folks like Nelson carrying two copies of APOE4.

But few assist companies can be found to assist folks take care of the implications of APOE4 testing, in response to interviews with greater than a dozen neurologists and genetic counselors. Alzheimer’s sufferers and caregivers face a scarcity of genetic counselors to elucidate the assessments and assist them navigate the psychological, medical, monetary and authorized penalties.

Eisai and Biogen’s Leqembi, which arrived available on the market in January, prices $26,500 a yr and isn’t lined by Medicare outdoors of scientific trials. Medicare has mentioned it is going to broaden protection if the drug is granted full U.S. approval, anticipated this summer season.

“Once you study that data, you are probably studying details about your siblings, about your youngsters,” mentioned Emily Largent, a bioethicist and well being coverage knowledgeable on the College of Pennsylvania Perelman Faculty of Drugs.

“Individuals describe feeling existential dread.”

As a scientist, Nelson understood intellectually what her APOE4 outcomes meant, however they created emotional havoc for her household.

She had inherited one copy of APOE4 from her mom and the opposite from her father, who was exhibiting no signs of Alzheimer’s on the time.

When her father’s reminiscence started to fail a yr later, certainly one of her two sisters doubted it might be Alzheimer’s, Nelson mentioned. Nelson knew he needed to have the illness, due to her genetic take a look at outcomes.

The assessments additionally confirmed that every of Nelson’s three grownup daughters had one copy of APOE4, which triples or quadruples the danger of creating the illness – confronting them with their very own Alzheimer’s dangers together with their mom’s.

Nelson’s daughter, Lindsey, 22, and a fourth yr nursing scholar at New York College, mentioned she was traumatized when, even earlier than testing, Nelson talked about exploring assisted suicide quite than undergo her mom’s destiny.

“I’d yell at her, cowl my ears and run away,” Lindsey mentioned. “There are various sophisticated feelings concerned.”

Nelson’s eldest daughter, Lexi, 24, who works in knowledge analytics, turned to analysis exhibiting that way of life modifications equivalent to weight lifting can enhance cognitive operate. “I’ve tried actually laborious to enhance my sleep, I’m exercising quite a bit,” she mentioned.

Her youngest, Pam, 20, a sophomore biology main at UCLA, mentioned she takes consolation in realizing that her mom’s outcome isn’t a prognosis. “It is only a threat issue, and there are numerous different elements that affect what is going to occur.”

Leqembi isn’t appropriate for Nelson, who isn’t symptomatic. Even when she had been eligible, she mentioned she isn’t a fan due to the danger of mind swelling, which is greater for folks with two copies of APOE4.

Nelson is pinning her hopes on an experimental capsule from Alzheon Inc, which is being examined in folks with early Alzheimer’s who’ve two copies of APOE4.

She is working her method by way of a bucket listing of journeys. In February, she climbed Mt. Kilimanjaro to boost cash for a most cancers charity, and she or he want to go to Patagonia, the Greek Islands, South Africa, probably Antarctica.

If remedy fails, she mentioned she has her “exit plan”: authorized euthanasia by way of a clinic in Switzerland. “I don’t need to stay the way in which my mother needed to stay her final 5 years of life. She was depressing,” she mentioned.

THE TESTING REVOLUTION

Till not too long ago, most medical doctors tended to not order genetic assessments to find out Alzheimer’s threat, as a result of there have been no efficient remedies to sluggish or stop the illness.

That modified with Leqembi, which was proven to scale back the speed of cognitive decline by 27% in sufferers with delicate Alzheimer’s. Eli Lilly’s donanemab is in scientific trials with outcomes anticipated by June.

Each medication take away the buildup within the mind of amyloid plaques related to Alzheimer’s, and are seen as a primary step in the direction of much more efficient remedies. Each could cause swelling and microbleeds within the mind. US regulators suggest genetic testing earlier than beginning remedy with Leqembi.

“With this drug, it behooves us to test,” mentioned Dr. Sarah Kremen, a neurologist at Cedars-Sinai in Los Angeles.

Within the 4 months forward of U.S. approval of Leqembi in January, APOE4 testing amongst folks over 55 who visited a health care provider throughout the final 30 days elevated 125%. From September 2022 to January 2023, the speed averaged 1.4 assessments per 100,000 sufferers, in contrast with 0.6 assessments per 100,000 sufferers in the identical interval a yr earlier, the evaluation by Seattle-based Truveta discovered.

The evaluation was based mostly on a assessment of medical information from 7.9 million adults at 28 main U.S. hospital techniques. It doesn’t embrace at-home client assessments.

The Nationwide Institutes of Well being estimates as much as 25% of individuals in the USA have one copy of APOE4 and as much as 5% have two copies.

But there’s a scarcity of genetic counselors to assist households take care of the implications of getting two copies of APOE4.

A 2018 research within the European Journal of Human Genetics discovered the U.S. had only one skilled genetic counselor per 82,000 folks. The UK had 1 per 193,500.

Banner Alzheimer’s Institute in Phoenix, which is testing Lilly’s donanemab, is researching an interactive on-line platform to ship APOE outcomes to volunteers being screened for enrollment within the trial.

“We would have liked a scalable approach to warn folks in regards to the potential advantages and dangers of genetic disclosure,” mentioned Dr. Eric Reiman, Banner’s director.

Whereas the U.S. Genetic Info Nondiscrimination Act (GINA) bans discrimination in employment and medical health insurance, it doesn’t cowl long-term care and incapacity and life insurance coverage.

Some members of households with elevated genetic threat of Alzheimer’s say it could be higher to not know in any respect.

Dovie Bryant, 77, who’s collaborating within the Lilly trial, misplaced her mom to Alzheimer’s in 2012.

When she shared together with her 5 siblings that she had one copy of the APOE4 variant, none wished to search out out their very own standing.

Her brother Jim Painter, 71, mentioned he feared testing may make it more durable to move a well being screening to maneuver right into a retirement neighborhood that gives rising ranges of care as an individual ages.

“That could be a purple flag,” Painter mentioned.

Reporting by Julie Steenhuysen; enhancing by Caroline Humer and Suzanne Goldenberg

Our Requirements: The Thomson Reuters Trust Principles.