“I cannot tell you how much it means to me that my extra chromosome might lead to the answer to Alzheimer’s,” Frank Stephens, a self-advocate with Down syndrome, told Congress in 2017. His heart-wrenching comment, which was followed by thunderous applause and a standing ovation, got it exactly right.
People with Down syndrome have an extra copy of the 21st chromosome — the chromosome on which the gene that codes for amyloid precursor protein is located. The accumulation of amyloid plaque in the brain is associated with the development of Alzheimer’s. Though the amyloid theory of Alzheimer’s is controversial, one thing is clear: Around 70% of people with Down syndrome will be diagnosed with Alzheimer’s in their 40s and 50s.
But not all hope is lost. Five years after Frank Stephens testified, there are promising, repurposed drugs for Alzheimer’s disease. In its first phase II trial, a new medicine called Leukine boosted cognition and memory scores and improved all three biomarker measurements for dementia. In addition, promising new drugs known as monoclonal antibody treatments — or mAbs — are now coming online in the United States. In July 2021, the Food and Drug Administration approved the first such treatment. Another followed this year, and a third showed promise in a phase 3 study, according to an announcement from Eli Lilly on Wednesday.
But barriers to Alzheimer’s drug accessibility remain. In April 2022, the Centers for Medicare & Medicaid Services severely restricted coverage of mAbs for Alzheimer’s. Only Medicare and Medicaid patients participating in CMS-approved clinical trials and data registries to develop more evidence of the efficacy of mAbs will be able to get their prescriptions covered — notwithstanding FDA approval.
If there’s one silver lining, it’s that, after a wealth of input from the Down syndrome community, the determination was finalized without discriminatory language originally included in a January 2022 draft. In that version, CMS specifically called out patients with Down syndrome as not being eligible to participate in such trials.
But the general restriction on coverage remains, as does its disproportionate impact on people with Down syndrome. Simply removing language barring people with Down syndrome from participating in clinical studies — without apology — is not enough. CMS must encourage the Down syndrome community to participate.
A National Institutes of Health working group has already laid out ways to do so. Among other things, they recommend using pictures to communicate about informed consent, increasing the number of check-ins with participants, and conducting home or remote visits during the study period to reduce travel burdens. And it certainly wouldn’t hurt to hold outreach events to engage with patient groups or make individuals with Down syndrome part of the research team itself.
These small steps could change the lives of more than 400,000 Americans with Down syndrome. That’s almost 1 in every 700 babies born in the United States each year, according to the Centers for Disease Control and Prevention. Despite this, Down Syndrome has been the least funded major genetic condition, and federal spending on Down syndrome declined from 2001 until my organization and our self-advocates successfully advocated for the establishment of the trans-NIH Down syndrome research initiative in 2018.
In 2009, after learning that my daughter Sophia would be born with Down syndrome, I co-founded the Global Down Syndrome Foundation. Our efforts have helped more than quadruple funding for Down syndrome research, with a large percentage going to Alzheimer’s research for people with Down syndrome.
Such research stands to benefit all people with Alzheimer’s. If scientists can figure out why a small fraction of people with Down syndrome never develop Alzheimer’s symptoms, they might even be able to develop an effective prevention method for the disease.
For now, though, we’re starting to see results with mAbs.
The treatments are by no means perfect. They don’t work for everyone, and some patients experience side effects. But in lots of cases, mAbs have helped to slow the decline of memory and thinking in Alzheimer’s patients.
If CMS keeps its onerous restrictions on coverage for these treatments in place, too many Alzheimer’s patients, including many youthful people with Down syndrome, will find their symptoms progressing past the point at which research has shown they may benefit from mAbs. These patients have no time to lose.
As Frank Stephens stated in his famous testimony, “It’s likely that this thief will one day steal my memories — my very life — from me.”
I have fought so hard to make sure that my daughter and everyone with Down syndrome can live a longer, healthier life and reach their true potential. The thought of my daughter one day losing to Alzheimer’s memories that are integral to who she is as a person is unbearable, which is why I’m working so hard to keep that from happening.
Michelle Sie Whitten is president and CEO of the Global Down Syndrome Foundation.