Focus area I
Longitudinal patient study
Characterize how BPAN changes over time: brain structural integrity, inflammation, iron accumulation (MRI), genetic mutations, and shifts in proteins and lipids, alongside standard clinical assessments.
Home / The Science
A bet that pays off twice.
Our flagship investment is a comprehensive initiative at the Stanford School of Medicine, designed to change the future for children with BPAN, and to illuminate the biology behind adult dementias.
The initiative
Led by Stanford Medicine.
The program is led by pediatric neurologist and neuroscientist Dr. and a cross-disciplinary team spanning pediatric and adult neurology, imaging, genetics, and epilepsy.
It’s a first-of-its-kind effort to uncover BPAN’s disease signatures and to screen thousands of drugs, including many already approved for other conditions, for the ability to correct the deficits at the heart of the disease.
Our approach
A meeting of the minds.
We study BPAN patients like Isa, and her non-BPAN siblings as controls, in a way designed for rapid discoveries that lead to successful treatments.
Focus area II
Cell & animal mechanisms
Determine the mechanism of BPAN-related neuronal cell injury and death, providing concrete targets for clinical therapy development.
Focus area III
Therapeutic strategies
Identify which treatments are most likely to succeed now: gene- and protein-replacement, stem cell, small-molecule, antioxidant, and anti-inflammatory therapies delivered to the brain.
Focus area IV
Open collaboration
Bring leading experts together by topic area to set priority research areas and promote the rapid discovery of targets for intervention.
The roadmap
Three research pathways.
Pathway I
Biomarker identification
Find measurable signatures of BPAN, to identify who is at highest risk and to track whether a treatment is working.
Pathway II
Drug screening
High-throughput screening of thousands of compounds, including FDA-approved drugs, to find candidates that correct the disease’s autophagy defects.
Pathway III
Brain organoids
Model BPAN in human brain tissue grown in the lab, a powerful platform to validate targets and test therapies.
Research progress
Momentum, milestone by milestone.
Thanks to generous donors, the work is already advancing. Here is where it stands today, with the latest shared by our partners at Stanford Medicine and the Lucile Packard Foundation for Children’s Health.
- Milestone 01
Building the foundation
Assembled a cross-disciplinary Stanford team and launched the first-of-its-kind BPAN research program.
- Milestone 02
A faithful disease model
Established a BPAN mouse colony that reproduces the disease, developing progressive epilepsy alongside cognitive and motor impairments, giving the team a living system to test ideas against.
- Milestone 03
A drug-screening engine
Built a high-throughput screening platform to test large libraries of compounds, including FDA-approved drugs, for the ability to correct the underlying biology of BPAN.
- Milestone 04
Reaching more families
Connecting with more patients and families to deepen the natural history of BPAN and prepare for future clinical trials.
- Milestone 05
Reading the disease
Developing MRI measures and biomarkers from BPAN-derived cells to detect the disease earlier and tell whether a treatment is working.
Milestones summarized from our partners at Stanford Medicine and the Lucile Packard Foundation for Children’s Health. Read the full updates →
The Stanford team
Many of Stanford’s top minds, on one rare disease.
Led by pediatric neurologist and neuroscientist Dr. Juliet Knowles, the program unites pediatric and adult neuroscience so BPAN can be studied as a window into neurodegeneration across the lifespan.
- Juliet Knowles, MD, PhDPrincipal investigator, pediatric neurology & neuroscience
- Frank Longo, MD, PhDAlzheimer’s & Parkinson’s disease expert
- Tony Wyss-Coray, PhDAging & systemic factors in brain health
- Sergiu Pașca, MDBrain organoids & stem-cell models
- Rebecca Levy, MD, PhDStanford School of Medicine
- Jonathan Long, PhDMetabolism & chemical biology
- Jennifer McNab, PhDAdvanced neuroimaging
- Christopher Lee-Messer, MD, PhDNeurology & computation
Supported by the Stanford Wu Tsai Neurosciences Institute, the Stanford Alzheimer’s Disease Research Center, the Knight Initiative for Brain Resilience, and the pediatric epilepsy center at Lucile Packard Children’s Hospital Stanford.
Funding the work
The infrastructure is in place.
About $1.7M was raised toward the science before the Foundation’s involvement. Since then, the Foundation has added a $500,000 gift and helped raise more, bringing the total to about $2.46M toward the $4.3M initial goal, which funds the faculty plus Pathways I and II. A $2.4M future goal adds Pathway III, roughly $6.7M for the full program.
Philanthropy sets the pace. Every gift accelerates the timeline to a treatment.
$2.46M raised
of a $4.3M initial goal · ~$6.7M for the full program
Where the goal goes
- Dedicated faculty & researchers
- Pathway I: Biomarker identification
- Pathway II: High-throughput drug screening
- Pathway III: Brain organoids (future goal)
Initial · $4.3MFuture · $2.4MTotal · $6.7M
The link
Why this matters for millions.
BPAN behaves like a very accelerated form of the neurodegeneration seen in Parkinson’s and Alzheimer’s. All three share a breakdown in autophagy, the brain’s recycling system.
So by studying BPAN early in childhood, researchers may uncover targets that help children today, and adults facing the most common dementias tomorrow. That is the bet that pays off twice.
Hallmark characteristics
BPAN beside Parkinson’s and Alzheimer’s.
Prepared with ToxSynergy, the comparison maps the shared and distinct features of severe BPAN, , Parkinson’s, and Alzheimer’s. The full document is embedded and downloadable below the summary table.
| Disorder characteristic | Severe BPAN | Rett Syndrome | Parkinson’s | Alzheimer’s |
|---|---|---|---|---|
| Differences | ||||
| Known initial insult (cause) | Yessingle mutation, X chromosome | Yessingle mutation, X chromosome | No | No |
| Onset age (years) | 1+ | 1+ | 60+ | 60+ |
| Gender bias | Often lethal in males | Often lethal in males | Male (2×) | Female (2×) |
| Seizures | Common | Common | Rare | Uncommon |
| Delayed neurodevelopment | Common | Common | Uncommon | Uncommon |
| Similarities | ||||
| Brain location | Substantia nigra / cerebrum | Substantia nigra / cerebrum | Substantia nigra / cerebrum | Cerebrum |
| Sequence of pathology, the same events in the brain | ||||
| Endoplasmic reticulum (ER) oxidative damage ↑ cell debris, ↓ protein & lipid synthesis | ✓ | ✓ | ✓ | ✓ |
| oxidative damage ↓ energy production, ↑ cell debris | ✓ | ✓ | ✓ | ✓ |
| Autophagy dysfunction ↓ removal of cell debris | ✓ | ✓ | ✓ | ✓ |
| Iron accumulation inside and outside brain cells | ✓ | ✓ | ✓ | ✓ |
| Tangles of protein and lipid inside and outside brain cells | ✓ | ✓ | ✓ | ✓ |
| Neuronal cell injury & death ↓ cognitive ability, language & motor skills | ✓ | ✓ | ✓ | ✓ |
| Oligodendrocyte injury & death ↑ demyelination | ✓ | ✓ | ✓ | ✓ |
| Microglial cells & astrocytes injury & death ↑ brain inflammation | ✓ | ✓ | ✓ | ✓ |
| Neurodegeneration accelerates | ✓ | ✓ | ✓ | ✓ |
| High-dose biotin supplementation | ||||
| Reduces neurodegeneration clinical & experimental models | ✓ | ✓ | ✓ | ✓ |
The takeaway
A common final pathway.
Though the initial insults differ, the cascade of toxic events that follows, and that ends in neurodegeneration, appears to be nearly identical across all four disorders. High-dose biotin (vitamin B7) supplementation has been reported to reduce neurodegeneration in clinical and experimental models of these disorders.
The full document
Hallmark Characteristics, prepared with ToxSynergy.
Key points
Why Isabella is so important to study.
Isa has undergone extensive clinical testing since infancy, across multiple clinical departments, including an advanced infant brain MRI at Wolfson Children’s Hospital, which showed thinning of the corpus callosum and delayed myelination. These early datasets offer rare insight for longitudinal study over time.
- Clinicians involved in her care believe Isa may be among the youngest patients ever diagnosed with BPAN, with one of the earliest comprehensive clinical datasets collected on the disorder.
- No study has yet directly linked the pediatric cause to late-onset diseases like Alzheimer’s and Parkinson’s.
- Following Isa so early allows study during the active phase, increasing the ability to identify what drives brain-cell death.
Research & publications
The science, in the open.
Explore the work behind the mission, from our own scientific leaders to the global body of research on BPAN and childhood dementia.
Marc Fariss, PhD
Isa’s great uncle · early scientific guide · author of the cascade comparison (2025)
Lenn Murrelle, MSPH, PhD
Board Member · Scientific Advisor
Juliet Knowles, MD, PhD
Research lead, Stanford Medicine
Explore the global research
Research into BPAN and childhood dementia is happening worldwide. These live searches surface the latest peer-reviewed work, updated continuously.
References
Sources & papers.
Each headline figure links to a public report or peer-reviewed study. Where values are estimates, they are labeled as such.
- Childhood dementia burden: Elvidge KL, Christodoulou J, Farrar MA, et al. The collective burden of childhood dementia: a scoping review (Brain, 2023). PubMed
- Childhood cancer mortality (U.S., ages 0 to 14): National Cancer Institute, Childhood Cancers. cancer.gov
- Mortality, diagnosis delay, family impact: Childhood Dementia Initiative, State of Childhood Dementia in Australia 2024. Report