The N-of-1 revolution: What ASOs mean for rare disease families
In rare disease, families are often forced into roles that extend far beyond caregiving. When faced with diseases for which no treatment exists, parents have often moved into health policy and patient advocacy to push therapeutic development in an area with low demand and commercial prospects. In some instances, parents have even founded research organizations or biotech start-ups to accelerate drug development for patients who have no therapeutic alternatives and often may not have the luxury of time.
The advent of antisense oligonucleotides (ASOs) has created a feasible path for personalized therapies that can be highly effective for patients with rare diseases. This n-of-1 approach is gaining momentum across gene therapy as well, with successful instances of bespoke CRISPR gene editing. In this blog, we highlight landmark cases where families acted as catalysts for innovative development.
When families become the R&D engine
One of the most widely recognized examples is milasen, a custom ASO created to treat Mila, a 6-year old with a rare genetic disease (Batten’s disease). Within 1 year of identifying the genetic mutation, the team at Boston Children’s Hospital - led by Timothy Yu - administered milasen. Unfortunately, while she experienced a short period of symptom alleviation after receiving the ASO, the disease had reached an advanced stage and she passed away.
In the wake of the loss of her daughter, Julia Vitarello decided to help prevent similar tragedies by increasing accessibility and scalability of n-of-1 therapies. She went on to found Mila’s Miracle Foundation to help fund and support individualized medicine by working with academics, clinicians, and regulatory bodies. She also founded N=1 Collaborative to enhance open science and data sharing among people and organizations who are developing n-of-1 therapies. Recently, she co-founded a biotech start-up, EveryONE Medicines, that aims to develop an ASO library and push for suitable regulatory pathways for this approach.
Families as catalysts, partners, and storytellers
In another example of families pushing for access to individualized therapies, parents of Susannah, a young girl with KIF1A-associated neurological disorder (KAND), partnered with the n-Lorem Foundation, which develops personalized ASOs at no charge for nano-rare patients. She experienced significant symptom alleviation and is still in stable condition 20 months later.
Building on that experience, Sloane, another child with a KIF1A mutation, later received the same ASO originally developed for Susannah. This was largely due to efforts of her mother and grandfather, who found n-Lorem through the KIF1A.org community. Her grandfather came out of retirement to support research funding initiatives for the rare disease community.
Taken together, these cases show that families are not only beneficiaries of individualized therapies; they are frequently the initiators and sustainers. They catalyze programs, partner with clinicians on design and monitoring, and document outcomes to inform regulators and future patients.
Finding peace in helping others
While many families initiate or drive the development of individualized therapies, in other cases their contribution takes a different form. For the Hermstads, the impact came not from launching a program but from the way their daughters’ experiences continue to guide research.
Jaci Hermstad had an aggressive form of FUS-ALS. Her twin sister, Alex, had passed away from the same condition a decade earlier. The ASO jacifusen was developed for her and administered just 4 months after diagnosis, but the disease had progressed too far. She died in 2020 at age 26 and her tissues (and her twin sister’s) were donated to help advance research. These samples, together with data from genetically engineered mouse models, formed the scientific foundation that allowed jacifusen to move forward. Today, Ionis Pharmaceuticals is conducting a Phase III trial in ALS patients with the same mutation.
Her mother expressed that the idea of her daughters helping others suffering from the same disease brings the family peace. Their story illustrates that families can contribute not only by driving therapies forward, but also by ensuring their experiences and generosity continue to benefit others.
Closing the rare disease gap
The path from mutation to medicine is technically feasible but not yet systematized. The above cases reflect how families often shoulder fundraising, logistics, and coordination. The FDA has issued draft guidelines that begin to define expectations for individualized ASOs across various domains, but navigation remains complex for non-experts.
However, there are still ethical concerns around accessibility. Individualized therapies remain limited to patients who can obtain a genetic diagnosis and connect with specialized research centers. For families in rural areas or without access to advanced testing, these opportunities may never arise. Even when programs do move forward, expansion beyond a single patient is uneven, raising broader questions about who benefits and how equitably.
Beyond cases where nonprofit foundations help cover costs, financial and insurance barriers remain major obstacles to access. Developing a bespoke ASO can cost $1–2 million or more per patient, covering design, manufacturing, and testing. Because these therapies often fall outside conventional frameworks, insurance coverage is limited or uncertain, leaving many families to rely on fundraising or philanthropy. To make individualized therapies viable at scale, new reimbursement models and funding approaches will be needed to support patients beyond those who can self-finance.
Toward a future where families do not carry the burden alone
The immediate goal is to turn bespoke successes into repeatable pipelines. This means starting with mutation triage to identify variants suited for ASO therapy, followed by validation in vitro using patient-derived cells. Manufacturing must be streamlined through shared processes, and safety can build on platform-based data rather than new studies each time. Clinical testing should then follow flexible designs adapted to ultra-rare populations. At Sano, we’re building the connective infrastructure that makes this future possible, helping families and researchers move from diagnosis to trial faster by streamlining recruitment, genetic testing, and follow-up.
Several groups are attempting to industrialize components of that pipeline, from nonprofit models that provide patient-specific ASOs for free, to companies building screening and design capacity for personalized oligos, to initiatives proposing libraries and shared manufacturing to compress timelines. Continued regulatory refinement and shared data will be essential so that future families are not required to rebuild the path case by case.
Families should not have to carry the burden alone. By pairing their determination with supportive trial infrastructure, we can turn extraordinary stories into ordinary options for patients everywhere.