Canavan Treatment

Canavan Treatment: A Look To The Future

Canavan disease is a fatal childhood genetic brain disease in which mutations in the ASPA gene prevent the normal activity of aspartoacylase (ASPA), a critical enzyme produced in oligodendrocytes (the affected brain cells in Canavan disease responsible for producing myelin and support overall brain health) that breaks down the neurochemical N-Acetylaspartate (NAA) into acetate and aspartate. When not properly broken down by functioning ASPA in oligodendrocytes, NAA accumulates, acetate and aspartate are depleted, and myelin production and brain function decline. Myelin is the insulation that coats axons and, in the brain, appears white, which is why it is also referred to as white matter. Myelin insulates the brain and spinal cord protecting nerve fibers and enabling normal transmission of nerve signals.

Currently, there are no cures for Canavan disease. Our goal is to change this outcome. Our Phase 1/2 clinical trial is a First-in-Human gene therapy study in patients with Canavan disease.

Diagnosing and Detecting Canavan Disease

Most children with Canavan disease are diagnosed during infancy. Signs appear between 3 and 6 months of age. They include poor head control, abnormally large head size, difficulty in eye tracking, excessive irritability, severely diminished muscle tone, and delays in reaching motor milestones such as rolling, sitting, and walking. Children with the juvenile form of Canavan disease may experience only mild developmental delays, such as difficulty speaking, unstable or slowed motor function or keeping up at school. Early diagnosis and treatment are key to improving a person’s quality of life.

New Gene Therapy Vector Technology for Canavan Treatment

The rAAV-Olig001-ASPA gene therapy is given as a one-time administration into fluid-filled cavities of the brain, called ventricles, and hence, the route of administration is called intracerebroventricular. This process enables the rAAV-Olig001-ASPA gene therapy to directly target the oligodendrocytes of the brain – the cells affected in Canavan disease and where the functional copy of ASPA gene needs to be delivered.

Canavan disease is an ideal candidate for this new technology because it is based on a single target, the ASPA gene, which codes for an enzyme responsible for breaking down NAA into acetate and aspartate. The ASPA gene mutation alters the activity of the aspartoacylase enzyme, resulting in an accumulation of NAA and depletion of acetate and aspartate that ultimately results in failure of brain growth and development.

Preliminary results show that patients treated in the Phase 1/2 First-in-Human clinical trial for Canavan disease have shown reductions in NAA levels, increases in white matter and myelin, and patient improvements within six months of treatment.

The Future of Canavan Treatment: ASPA Gene Delivery

We have been leading the way in research and development for a Canavan treatment option. We are currently developing rAAV-Olig001-ASPA gene therapy to deliver a therapeutic ASPA gene directly to the oligodendrocyte cells, the cells responsible for producing myelin.

The gene therapy process begins by administering the rAAV-Olig001-ASPA directly into the fluid that surrounds the brain and spinal cord (cerebrospinal fluid, or CSF), allowing the gene therapy to spread across many cells. The gene is packaged using a unique adeno-associated virus (AAV) vector that targets oligodendrocytes specifically. The virus is designed to deliver ASPA to the cells, but not replicate, and not cause infection. Once the ASPA gene is inside the cells, researchers believe it may help the cells make aspartoacylase, the enzyme needed to break down NAA.

Though promising, the ongoing development of data is critical in determining the effects that the gene delivery has had on those who have received the treatment and provides a roadmap to further drug development and regulatory approvals. Data on the effects of gene delivery are essential for ensuring the safety and efficacy of the treatment, as well as furthering our understanding of how gene delivery works. As clinical development progresses, it is important to continually assess the effects of the treatment on the patients who have received it. These data can then be used to advance further drug development and regulatory approvals.

Coping With Canavan Disease

Coping with a diagnosis of Canavan Disease can be difficult and emotionally overwhelming, but there are strategies that can help families and patients cope. It is important to take care of yourself, both mentally and physically. Exercising, sleeping and eating well can reduce stress and help with managing emotional and physical pain. Support groups are also a great resource for families to find comfort and understanding from people who are going through similar experiences. Finally, it is important to take time for yourself and enjoy the positive moments with your loved one. Spending quality time together, such as going for a walk, reading books, creating a space that is soothing for relaxation, or doing sensory arts and crafts, can be a great way to make memories and create joy in the home.

On The Horizon for Canavan Treatment

Unfortunately, there is no cure for Canavan disease yet, but there is hope. We are encouraged by early clinical trial results and believe the unique ability of our technology to target oligodendrocytes may provide an avenue to restore oligodendrocyte function in Canavan and other devastating diseases in which myelin is affected and where treatment options do not exist.

Canavan Treatment