What Families Should Know About the n-Lorem Foundation?

Who is n-Lorem?

n-Lorem is a US-based nonprofit that designs, develops, and provides antisense oligonucleotides (ASOs) free for life to individuals with rare genetic disorders. ASOs are a form of precision medicine that target a specific genetic variant, so they are designed for one individual or a very small group of individuals who share similar variants.

To make this technology more accessible, n-Lorem has built a standardized process to do so at scale. They’ve developed a pipeline so that while each individual’s ASO is still uniquely designed for them, the steps taken to produce it follow a proven roadmap, rather than being reinvented for every new case.

How Does This Process Work?

STEP 1: A research physician submits an application. This is typically a neurologist or geneticist at an academic medical center who is willing to serve as the treating physician throughout the process. Families cannot apply directly, so identifying a willing and able clinician is the essential first step.

STEP 2: n-Lorem reviews the application. They ask several key questions to determine if the patient is a good candidate:

• Is their variant one that could realistically be targeted by an ASO?
• Does the disease primarily affect an organ that n-Lorem has experience targeting?
• Is the variant understood well enough to design an ASO and measure if it is helping?
• Does the individual have access to a qualified physician and institution?

STEP 3: ASO design and testing. Hundreds of candidate ASOs are screened in patient-derived cells (iPSCs), then narrowed down to identify which are the most effective. The best candidates advance to be tested for safety in animal models.

STEP 4: Investigational New Drug (IND) application is submitted. Data from the lab and animal studies are presented to the FDA for review. If approved, the ASO can move into a clinical trial.

STEP 5: Baseline data is collected. The participant is studied for at least 6 months before treatment begins so researchers can determine if there are any improvements following ASO administration.

STEP 6: Dosing begins. The ASO is administered typically every 3 months, starting at a low dose that increases gradually over time. Safety is monitored regularly throughout this process.

The Results So Far

As of July 2025, n-Lorem had received nearly 400 applications, accepted approximately 190 for treatment, and had around 35 patients who had actually started receiving an ASO.

Thirteen of these individuals have disorders that present similarly to KNQ2-DEE, including children with KIF1A-associated neurological disorders and SCN2A-related epilepsies. The treatment goals across this group focused on reducing seizures, improving motor skills, supporting neurodevelopmental and behavioral outcomes, and improving gastrointestinal function. After at least 6 months of ASO treatment, all 13 showed meaningful improvement in these domains, with some even recovering previously lost skills.

Importantly, no ASO-related serious adverse events have been reported in these individuals. Almost all side effects were associated with the administration process (lumbar puncture), which can cause headache and pain at the injection site.
To learn more about the n-Lorem experience, follow this link to their recently published article.

Connection to KCNQ2-related disorders

In many cases of KCNQ2-DEE, one variant copy of KCNQ2 produces a protein that actively works against the brain rather than supporting it. This happens either because the KCNQ2 variant produces a protein that is overactive (gain-of-function), or because the variant produces a faulty version of the protein that interferes with the function of healthy proteins (dominant negative). In both cases, the variant protein is problematic.

An allele-selective ASO approach, as used previously by n-Lorem, would be effective in these situations. By silencing the specific variant KCNQ2 copy while leaving the healthy copy alone, you can target the source of dysfunction while preserving what is working. This is one of the most well-established applications of ASO technology and is a promising direction for the KCNQ2 community.

Watch the KCNQ2 Power Hour webinar, covering this topic.