Alliance to Cure Cavernous Malformation (formerly Angioma Alliance)

Cycle 2

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Cavernous angioma, cavernoma, and cerebral cavernous malformation (CCM) are synonyms for mulberry-shaped abnormal blood vessels with thin, leaky walls. Cavernous malformations are commonly found in the brain or spinal cord. The most common first symptom is seizure, followed by hemorrhage and neurological deficits like blurred vision and weakness in limbs.

Last updated 04/30/2026

Clinical

Disease Class

Epilepsy and seizure disorders

Genetic diseases

Neurological diseases

Vascular disease

Body Systems

Cardiovascular / Circulatory

Nervous / Sensory

Organs

Blood vessels (veins, arteries)

Brain

Spinal cord

Known Genetic Link

Yes, one or more genes directly cause the condition

Causative Genes

CCM2

CCM3 (PDCD10)

KRIT1 (CCM1)

Contributory Genes

MEKK3

PIK3CA

Type of Inheritance

Autosomal dominant

Newborn Screening

Disease Mechanism(s)

Abnormal cell proliferation

Autophagy defect

Defective cell adhesion

Vascular/Angiogenesis Defects

mTOR pathways dysregulation

Age of Onset

Adolescence (12-17)

Adulthood (age 18-64)

Early childhood (age 1+-5)

Elderly (age 65+)

Infancy (age 0-1)

Middle childhood (6-11)

Average Age at Diagnosis

Adulthood (age 18-64)

Life Expectancy

Elderly (age 65+)

Affected Sex(es)

Female

Intersex

Male

National Prevalence

10000+

Global Prevalence

10000+

National Incidence

1001-10000

Global Incidence

1001-10000

Populations and/or ancestry with higher prevalence

Founder mutations exist in the Hispanic population of New Mexico and the greater Southwest, including Chihuahua/Sonora, among Ashkenazi Jews, and among a geographically dispersed group who can trace their heritage to the Southern region of Colonial America.

Symptoms / Phenotypes

attention disorders / ADHD

balance problems

behavioral changes

facial droop / unilateral facial palsy

fatigue

headaches / migraines

hearing loss / hearing impairment

hemorrhage/bleeding

muscle weakness

seizures / epilepsy

speech problems / apraxia

tinnitus

vasculitis

vision problems

Biomarkers

Diagnostic

· Investigative: various blood inflammatory markers

Monitoring

· MRI qualitative susceptibility mapping (submitted for FDA qualification)

Prognostic

· Investigative: various blood inflammatory markers

Existing Therapies

Drugs used off-label

Regulatory Agency-Approved for Symptom Relief

· anti-epilepsy meds

Therapies in Development

Antibody-based therapy (monoclonal antibodies, biologics)

· CD38 Monoclonal Antibody - in trial in China

Antisense oligonucleotide (ASO) therapy

Devices/medical equipment

Dietary & metabolic therapies (medical food, dietary restriction, supplements, etc.)

· Vitamin D, emulsifier-free diet

Gene therapy

· 2 gene replacement programs for CCM3

RNA interference (RNAi) therapy (siRNA, etc.)

· pre-clinical in various academic labs

Repurposed drug

· Too many to list (20+) are in pre-clinical screening. Aspirin near trials. Alpelisib - pilot. Propanolol completed mildly successful Ph 2A

Small molecule therapy (novel small molecule drugs)

· REC-994 superoxide dismutase - Ph2A ended, ACCM to pick up. NRL-1049 - ROCK inhibitor

Surgical & interventional

· Focused ultrasound nearing Ph 1/2

Therapeutic Development Stages

In clinical trials (Phase I, II, III, or IV)

In preclinical development

In research/exploratory phase

Therapeutic Development Role

Access to registry or natural history study

Data analysis

Data sharing

Focus group participation or coordination

Funding

Meetings with regulators (e.g., FDA listening sessions, PFDD meetings)

Other

· Pre-clinical research to de-risk. Project manage trial.

Outcome measures development

Recruitment and outreach to patients

Recruitment and outreach to trial sites / physicians

Results dissemination (including publications)

Sample provision

Study material design and/or review (not protocol) — includes patient-facing materials such as informed consent

Study protocol design and/or review (includes selection of outcome measures)

Organizational & Research

Cell Lines

iPSCs

Cell Lines, Institution

Cyagen

University of California San Diego (UCSD)

University of North Carolina (UNC)

Cell Lines, Involvement

Consulted

Funded

Own

Cell Lines, share

Some of our cell lines are freely available

Disease Model

C. elegans

Mouse

Organoids

Disease Model, Involvement

Consulted

Funded

Disease Model, share

Some of our disease models are freely available

Organizational Challenges

We are trying to learn to be a drug developer very quickly - regulatory filings, product liability insurance, drug storage & stability testing, etc. It's a bit overwhelming, and we could use support.

Clinical Trial Role

Data sharing

Meeting with regulators

Outcome measures, development

Recruitment and outreach, patients

Recruitment and outreach, trial sites/physicians

Study material design, review (not protocol)

Study protocol design, review

Clinical Trial Types

Observational

Phase 1

Phase 2

Biobank, Institution

Texas Heart Institute

Biobank, Involvement

Designed

Funded

Own

Center of Excellence, Institution

Ascension St. John's

Baptist Health

Barrow Neurological Institute

Beth Israel Deaconess Medical Center

Boston Children's Hospital

Cincinnati Children's Hospital

Duke University

Lurie Childrens Hospital of Chicago

Mayo Clinic

Mayo Clinic Jacksonville

Seattle Children's Hospital

Stanford University

Texas Childrens Hospital

University of California San Francisco (UCSF)

University of California, Los Angeles (UCLA)

University of Chicago

University of Miami

University of New Mexico

University of Pennsylvania (PENN)

University of Virginia (UVA)

University of Washington

Center of Excellence, Involvement

Consulted

Endorsed/Certified/Accredited

Registry

Yes, we have a registry that we created

Data Collected, Registry

Electronic health records/electronic medical records

Genetic data

Longitudinal natural history data

Medication usage

Patient contact info

Patient-reported data

Data Entered by, Registry

Other

Platform, Registry

Ordinal Data

Natural History Study

Yes, we have collaborated on a natural history study

Data Collected, Natural History Study

Clinical endpoints (outcomes)

Electronic health records/electronic medical records

Genetic data

Imaging data

Medication usage

Patient-reported data

Prospective data

Retrospective data

Platform, Natural History Study

REDCap

FDA Patient Listening Session

Yes

FDA Patient-Focused Drug Development (PFDD) Program

ICD Codes

We use an ICD-10 code capturing the family of diseases to which our disease belongs

Yes, we have an ICD-11 code specific to our exact disease

Diagnostic Guidelines

Yes, we have published formal guidelines in a peer-reviewed journal

Science Advisory Board Policies

Yes, willing to share SAB policies

Research Network Policies

Does not have a CRN

Patient Priority Survey

Yes

Patient Priority Survey, share

Yes, will share

Research Roadmap

Yes we have a Research Roadmap, and will share policies

None

Europe

North America

South America

Europe