A Promising Treatment for WWOX Associated Neurological Disorders

Aqeilan Rami, HUJI, School of Medicine - IMRIC, Immunology and Cancer Research



LifeSciences and BioTechnology   


epilepsy, rare disease, gene therapy

Current development stage

For pharmaceutical development: TRL4 - POC & Safety of candidate drug formulation is demonstrated in defined animal model




Germline mutations of WW domain-containing oxidoreductase (WWOX) has been documented in epilepsy, ataxia, autism, multiple sclerosis and disorders of sex development (DSD) patients. More recently, genetic meta-analysis of diagnosed Alzheimer’s disease identified the WWOX gene as a new risk locus. The most urgent and devastating disease with the WWOX mutation today is known as WWOX-related epileptic encephalopathy (WOREE) syndrome. Patients with WOREE exhibit growth retardation, intractable epilepsy, intellectual disability, and early death (few months to 2-3 years). Several lines of evidence strongly suggest that a WWOX expression is required for normal development and function of the central nervous system (CNS) and that mutations in WWOX result in neurological disorders. Currently, there is no treatment that could save children with WOREE.

Our Innovation

WOREE patients and all other WWOX-related disorders harbor no or an inactive WWOX.  Re-expression of intact WWOX could restore WWOX function and cure WOREE patients. A single intrathecal injection of WWOX is proposed to save WOREE patients and other WWOX-related disorders.


Viral particles containing the WWOX gene have been injected intracranially in the brains of WWOX null mice. The mice were followed in time and assessed for weight, blood glucose, and occurrence of seizures, behavior and fertility. Remarkably, a single injection of the gene could rescue the complex phenotypes of WWOX null mice. The treated mice continued to gain body weight, display normal glucose levels and did not show any signs of spontaneous seizures and ataxic phenotype. Additionally, the mice were fertile and able to breed (both males and females).


This is a gene therapy approach to treat and cure children having mutations in the WWOX gene to save their lives. Other indications may also include Multiple Sclerosis and Alzheimer.




Contact for more information:

Mel Larrosa
VP Business Development Healthcare
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