Targeting Folate Abnormalities
in Autism Spectrum Disorder

For nearly 20 years, I have devoted my career as a pediatric neurologist, research scientist, and clinician to finding ways to safely and effectively improve the lives of children with Autism Spectrum Disorder (ASD). Over that time, my team and I have explored many potential treatments. Among them, one has repeatedly stood out for a subset of children with ASD — leucovorin, a prescription-strength form of Vitamin B9 that has been used safely in oncology for more than 80 years.

I have led both open-label and double-blind, placebo-controlled clinical trials of leucovorin in children with ASD, and across these studies we have consistently observed meaningful, statistically significant improvements with treatment. These findings are also reflected in my daily clinical practice. I have personally treated hundreds of children with leucovorin and collaborated with other clinicians who together have treated thousands more. Behind these data points are children whose lives were meaningfully changed with this medication.

Reassuringly, similar blinded, placebo-controlled studies conducted in other countries have largely replicated our results. Some of these studies have even gone a step further, examining whether leucovorin can be safely used alongside antipsychotic medications, which are often prescribed to address irritability and agitation in ASD. These independent investigations have reached the same conclusion: leucovorin is a safe and effective treatment that can improve core symptoms of ASD, including communication and socialization.

Last year, my group collaborated with EveryCure, a nonprofit dedicated to identifying existing drugs that can be repurposed to help more patients. Working with EveryCure and its founder, Dr. David Fajgenbaum, MD, has been instrumental in raising awareness about the potential of repurposing leucovorin as a treatment for ASD and a related conditions called Cerebral Folate Deficiency (CFD). More information on this effort can be found here: https://everycure.org/cfd/

In parallel, the FDA recently announced that it is working with the original manufacturer of leucovorin to update the drug’s labeling to include treatment of Cerebral Folate Deficiency (CFD). This is a crucial step forward that will help more children gain access to a life-changing therapy.

First, leucovorin is a generic medication, produced by many different manufacturers. Each manufacturer uses its own combination of inactive ingredients, including dyes, excipients, and binders, some of which can be problematic for children with ASD who have gastrointestinal sensitivities or allergies. Many of these children also live with Avoidant/Restrictive Food Intake Disorder (ARFID) and intense sensitivities to taste and texture. Because this drug is typically available only as a solid tablet meant to be swallowed, this is simply not a feasible route of administration for sensitive patients and very small children who cannot swallow pills.

Second, even when parents are eager to try leucovorin, they frequently encounter systemic barriers. Because using leucovorin for ASD is considered “off-label,” many physicians are reluctant to prescribe it. Doctors may be unfamiliar with the dosing strategies, how to monitor treatment, or which patients are most likely to respond. Out of caution or uncertainty, they choose not to offer this option at all.

For families who do manage to obtain a prescription, there is another obstacle: supply. For many years, the current production of leucovorin has been strained by the needs of both oncology patients and the growing ASD population. Pharmacies often run short or completely out of stock, leaving families with a prescription in hand but no medication available.

Compounded leucovorin can be an alternative for some, but even compounding pharmacies may struggle to meet demand or to create a product that is consistently suitable for young children with sensory sensitivities. Over-the-counter folate products come in much lower doses than what is needed to treat CFD or ASD making them unreliable options. Dosing, taste, texture, consistency, and stability all matter deeply for this population, and too often, the available options fall short.

Because leucovorin is a long-established generic drug, large pharmaceutical companies have little financial incentive to invest in solving these problems. No one is motivated to optimize the formulation, improve tolerability, or design delivery specifically for children with ASD. As a result, a highly promising treatment remains far less accessible and workable than it could and should be.

That is why we are launching a new endeavor.

Eletala Enterprises is a newly founded company that I am leading to rethink drug development for the ASD community from the ground up. Rather than trying to “force-fit” existing leucovorin tablets into a population they were never designed for, we are starting with the real-world needs of children with ASD and their families and working backward.

Our first project is to develop a new formulation of leucovorin specifically for the ASD community. We are partnering with some of the world’s leading folate scientists to create a version of leucovorin that is:

• Colorless
• Tasteless
• Textureless
• More Potent & Efficient

Our goal is to refine what we already know leucovorin can do: to amplify its positive effects, preserve its excellent safety profile, and reduce the dose needed to achieve meaningful clinical improvements. In doing so, we aim to create a formulation that is not only medically effective, but practically usable for the very children who need it most.

In the course of development, we will add to the list of existing research and clinical studies to enhance our knowledge and continue building solutions for our ASD patients.

We are deeply motivated and hopeful. We believe this new approach to leucovorin holds the potential to positively transform the lives of many children with ASD and to finally align the science, the formulation, and the day-to-day realities of families living with autism.