Leading the worldwide fight to treat and cure
Tay-Sachs, Canavan, GM1 and Sandhoff diseases

Canavan Research

Canavan Research Overview

Canavan is a progressive neurological genetic disorder caused by the absence of a vital enzyme known as aspartoacylase (ASPA). ASPA breaks N-acetylaspartate acid (NAA) into acetate: the building blocks essential for building myelin. Myelin is a fatty membrane (also known as white matter) that forms a protective coating around each nerve ensuring the nerve functions properly. It is one of over 40 genetically inherited disorders known as Leukodystrophies.

Where are we with Canavan research and therapies?

ONGOINGNatural History Study of Patients With Canavan Disease, CANinform (sponsored by Aspa Therapeutics)
CANInform, the Canavan disease natural history study, will be the first multinational effort to rigorously gather both retrospective and prospective data from this patient population. Data collection will include extraction of retrospective data from medical records of living patients and deceased patients, and collection of prospective, longitudinal data from living patients and their parent(s)/caregiver(s). Motor function assessments will be performed in the home by qualified study team members. In addition, families will be invited to attend clinic visits or will be followed by the clinical site remotely for up to 3 years. 

ENROLLING - Aspa Therapeutics Gene Therapy Program, CANaspire, is recruiting. Learn more here.

ENROLLING - Myrtelle LLC, Gene Therapy at Dayton Children's Hospital, Ohio. Learn more here.

Gene Therapy

Historical insight

An AAV2 gene therapy trial was conducted in thirteen patients with Canavan Disease, to assess long term safety and to see if the treatment was beneficial. The long term results (minimum of five years post treatment) have shown that are were minimal adverse effects from using this treatment. Additionally, the patient's NAA levels decreased, which slowed the progression of cell death in the brain. Overall, some clinical improvement was seen in the patients. The authors believed that for this therapy to be most effective, it would have to be administered at a very early age (possibly less than four months.) Thus, further research into early diagnosis is essential. 

Read the full publication Long-Term Follow-Up After Gene Therapy for Canavan Disease

Further studies using adeno-associated viruses (AAVs) have been performed in animal models. The most promising of these for Canavan Disease is the recombinant AAV-mediated gene therapy. BridgeBio is honored to have licensed the Canavan Gene Therapy program developed by Dr. Guangping Gao at UMASS Medical School. They will be working with Dr. Gao and UMass Medical School to move this forward as fast as the science and regulators will allow us to go. Aspa Therapeutics was created to advance this gene therapy and with sound natural history data from families will help get them to the next step - clinical trials.

Actalzolamide Trial

Actalzomide is a drug which can be used to treat epilepsy, glaucoma, and other diseases. A trial using this drug was conducted in patients with Canavan Disease in 1998. The aim was to reduce water concentration and NAA levels in white matter over 5 months. Although it did not reduce either of these, this drug did reduce intracranial pressure.

Ketogenic Diet

Novotny Jr et al. (1999.) This diet increased the levels of beta-hydroxybutyrate in the brain, but did not affect the NAA levels.

Lipoic Acid

Research done by Pederzolli et al. (2007) found that lipoic acid may be a good approach for therapeutic treatment, because it crosses the blood brain barrier. Trials have been done in rats. The results suggest that this could be a good treatment for the symptoms of Canavan Disease.

Acetate Supplement

This approach is based on the theory that the myelin destruction seen in Canavan is caused by low levels of acetate. By supplementing acetate, normal myelin production and maintenance can occur. Unfortunately, this does not address the accumulation NAA.

After a study conducted by Madhavarao et al (2009) that found that this treatment may help with symptoms, Segel et al (2011) tested acetate supplementation in human newborns. Although there were no significant harms, no motor improvement was found either.


After studies in rats found that lithium injections helped drop NAA levels (O’Donnell et al., 2000), trials were done in patients with Canavan Disease. After one year of treatment brain and urine NAA levels were decreased and alertness and visual tracking both improved. However, muscle tone and spastic dysplegia did not improve (Solsona et al., 2012).

Enzyme Replacement Therapy

Enzyme replacement therapy is challenging in Canavan disease, because molecules need to be able to cross the blood brain barrier. Different modalities intended to help with this have not shown any quality of life improvements in patients.

Natural History Study 

Natural history studies continue to be an essential part of the case getting clinical trials funded. Data is a measurement of whether a treatment, in clinical trial, is successful or not. NTSAD funded a project, "Defining the Natural History of Canavan Disease through Development of an International Registry," with co-investigators, Heather Lau, MD and Paola Leone, PhD. 

ONGOINGNatural History Study of Patients With Canavan Disease, CAN Inform

Other NTSAD funded Canavan projects include:

  • Development of an in vitro approach to identify molecular pathways of Canavan disease (Traka) - read full summary here.
  • Gao - Optimization of Efficacious Gene Therapy for Canavan Disease 
  • Quantitative description of the clinical course of Canavan disease (Bley - Million Dollar Bike Ride grant recipient) - read summary here.

Learn more at NTSAD Research Projects - 2002-2018 Funded Research.

Stem Cells

Leading stem cell researchers are exploring the potential therapeutic effects of stem cells in Canavan disease. Stem cell therapy is still an emerging field; potential therapies or clinical trials using stem cell therapy are not immediate. 


For more information, see All about Leukodystrophies Diseases

Read about Dr. Guangping Gao, a world leading Canavan Disease Researcher! 

Information for this page was taken from  Making the White Matter Matters: Progress in Understanding Canavan’s Disease and Therapeutic Interventions Through Eight Decades written by Seemin S. Ahmed and Guangping Gao, published in 2014.