An Avalanche of Advances in Human Genetics

For the first time in 35 years of writing and revising my textbook Human Genetics: Concepts and Applications, I’m happy to report good news – real progress, and not hype.

The strides in 2025 range from effective gene therapies and drugs for devastating neurological conditions to a novel new painkiller. Here’s a closer look at the good news!

Gene Therapy for Sanfilippo Syndrome
DNA Science first covered the story of Eliza O’Neill in 2014, here, when the parents of four-year-old Eliza, a vivacious, active, and adorable little girl, learned that she had inherited the rare brain condition Sanfilippo syndrome type A.

Her dad Glenn O’Neill remembered:
“’We found out the terrible news today. For now, I want to focus on her wonderful personality and life every day. One of my goals is to keep her happy and smiling for as long as possible. I love her so much.’

This was my journal entry on the evening of July 17th, 2013. I never kept a journal before this. Earlier that day, our 4-year-old daughter Eliza was diagnosed with a rare terminal genetic disease called Sanfilippo syndrome type A. In one terrifying instant, we were told that we would have to watch Eliza fade away before our eyes. My journal entry words reflected the lack of hope a parent first feels when told their child has a disease that has no cure and no treatment.‘

Eliza and other children with this disease are missing an essential enzyme for normal cellular function. Over time, a toxic material called heparan sulfate builds up in the brain and body, leading to severe disability and death before they even reach their teens. This disease affects both genders, all races, all countries and continents.’”

My textbook’s chapter on gene therapy opens with a photo of smiling Eliza, in bed as the gene therapy drips into her bloodstream. In the following years, when I asked for details on improvement, Eliza’s parents couldn’t say much, because the clinical trial was ongoing and it takes years to assess findings. Their social media posts remained vague yet upbeat, relating their many fundraising events with the occasional photo of Eliza swimming or running about.

But then I was thrilled to discover Eliza’s mom, pediatrician Cara, updating Eliza’s progress on August 26, 2025, in The Hill. The account brought me to tears.

“In 2016, at 6 years old, Eliza got her chance. She was the first to receive UX111, and afterward began sleeping through the night in her own bed for the first time. Today, she’s not only outliving the average life expectancy for Sanfilippo A (15 years) but also regaining non-verbal communication skills, jumping on trampolines at the bounce park, and using a fork to eat at an age at which most patients require a g-tube for nutrition.

Another child who received a higher dose of UX111 treatment at 2 years old is showing even more dramatic benefit. Now 10, she is reading, plays on a softball team, and hangs out with her friends. Reflecting on the eight years since gene therapy, her mom says, ‘It’s given my daughter a rich and happy life.'”

A New Painkiller
A 10-year-old boy in Pakistan came to fame from his astonishing inability to feel pain. As a street performer, he would walk on hot coals and insert daggers through his arms before stunned crowds – feeling absolutely no pain. He died at age 13 from jumping off of a roof, thinking himself impervious to all injury.

In 2006, researchers in the UK investigated three families from the same area of Pakistan, a nation where about 60% of marriages are between cousins. They found six members of the families, all age 14 or younger, who also couldn’t feel pain.

They all shared a mutation in the gene SCN9A, which encodes one of three types of sodium channels. The condition is a “channelopathy.” A variant of the odd phenomenon, from the same gene, is “burning man syndrome,” which DNA Science covered here.

Investigation of the sodium channel SCN1A led to development of the new drug Journavx (suzetrigine), thanks to researchers at Yale University and an extended family living in a neighborhood in Alabama whose members experience chronic pain.

The drug became available in 2025. This video shows how the drug alleviates moderate-to-severe acute pain. Blocking sodium channels in the peripheral nervous system can enable patients to avoid opioids. The drug is used for short-term pain from surgery, dental procedures, and trauma.

A Way to Slow Huntington’s Disease
HD is an insidious, intractable, movement disorder. It arises from a triplet repeat mutation that causes the encoded protein huntingtin to become long and sticky, gumming up brain parts. Movements become uncontrollable and exaggerated, while personality changes. DNA Science covered the advance here.

The treatment, for now called AMT-130, significantly slows progression of the disease and may become available next year. It was developed at biotech company UniQure.
AMT-130 is a gene therapy injected, one time, into the brain. It delivers not genes, but microRNAs that glom onto the mRNA molecules that carry the information from the overextended gene, which encodes a protein called huntingtin.

The new treatment so far appears to slow decline by a factor of four, so that what typically happens by a year takes four. That’s a gamechanger, HD families say. About 75,000 people have HD in the US, UK, and Europe.

Two other brain diseases recently announced treatments: progeria and Alzheimer’s.

Progeria
The rapid-aging condition Hutchinson Gilford Progeria syndrome, aka progeria, is one of the most heartbreaking single-gene diseases. In a matter of years, children come to starkly resemble the aged.

When DNA Science covered the repurposing of a cancer drug, lonafarnib (Zokinvy), to treat progeria in 2014, average lifespan was only 14.6 years. Today, although that average remains in the teens, outliers are beginning to accrue – a few treated patients have survived into their twenties.

FDA approved the drug, which increases life expectancy by about 2.5 years, in late 2020. Now a second drug, progerinin, is being developed, as well as a gene editing approach to slow the rapid aging. Because of the extended survival made possible with these new treatments, progeria is now said to affect children and young adults, not just children.

Alzheimer’s disease
In Alzheimer’s disease, accumulation of two types of protein gradually gum up the brain. Amyloid beta forms plaques outside brain cells, while tau forms tangles mostly outside the cells. The amygdala (seat of emotion) and hippocampus (the memory center) are especially vulnerable.

FDA approved two drugs that can slow the progression of Alzheimer disease by targeting amyloid beta: Leqembi (lecanemab) in 2023 and Kisunla (donanemab) in 2024.

Leqembi is a monoclonal antibody given by infusion every two weeks to patients with mild cognitive impairment (MCI) or who have progressed to early Alzheimer’s dementia. It directly targets amyloid beta, slowing its accumulation. However, long-term efficacy isn’t yet known, and amyloid beta can begin to accumulate if the person stops taking the drug.

Donanemab (Kisunla), also an infusion, decreases plaques, leading to a 22% slowing of decline in patients with MCI or mild dementia. However, the tenacious amyloid builds up again if a patient stops taking either drug. Both are still being assessed for long term effects.

On October 13, FDA approved pTau181, the first test for tau protein. So far, it’s used to rule out eventual Alzheimer’s in patients with MCI or mild dementia. Elevated tau presages the disease in about 97 percent of cases.

“By bringing Alzheimer’s blood-based biomarker testing into primary care, we can help patients and their clinicians get answers sooner to support them earlier in their journeys,” said Brad Moore, President and CEO of Roche Diagnostics North America.

CODA: On Breakthroughs

A recent report in The New England Journal of Medicine on gene therapy for adenosine deaminase deficiency – aka ADA-SCID or bubble boy disease – illustrates the absurdity of the word “breakthrough” to describe medical advances. The journey from idea to success often takes decades.

A missing enzyme lies behind ADA-SCID – severe combined immune deficiency due to adenosine deaminase deficiency. Prior to gene therapy, children with ADA-SCID received regular infusions of the missing enzyme, along with antibiotics and antibodies to ward off infection. But without a bone marrow transplant from a matched donor, they survived only two years.

I told the story of gene therapy for ADA-SCID in my book The Forever Fix: Gene Therapy and the Boy Who Saved It. The trial was at the NIH Clinical Center in Bethesda:

“The very first gene therapy for an inherited disease happened on September 14, 1990. On that Monday afternoon, four-year -old Ashanthi DeSilva received an infusion of her own T cells, bolstered with working copies of a gene that her failing immune system desperately needed.”

My book chronicles the many setbacks that the field of gene therapy has had to overcome. And so the new report for ADA-SCID is indeed exciting – of the 62 kids in the trial, 59 developed an immune response, even responding to vaccines, and all survived.

The two leaders of the project took both a narrow and broad view.

Said Don Kohn, a distinguished professor of microbiology, immunology and molecular genetics at UCLA who has been working on the gene therapy for decades, “These results are what we hoped for when we first began developing this approach. The durability of immune function, the consistency over time and the continued safety profile are all incredibly encouraging.”

Added first author Claire Booth, from UCL Great Ormond Street Institute of Child Health, “Almost 100% of the patients we’ve treated with gene therapy for ADA-SCID have been cured. This is reassuring for other conditions treated using the same techniques – it works in the long term and is safe.”

It is sobering that the “breakthrough” of gene therapy for ADA-SCID took 35 years! But with gene editing added to the toolbox, I’m looking forward to further success.