Canavan Disease

Unlocking Hope: Advancements and challenges in Canavan Disease cure

In the intricate tapestry of genetic disorders, Canavan disease emerges as a poignant thread, weaving through the complexities of neurodegenerative challenges. Canavan disease, also known as Canavan-Van Bogaert-Bertrand disease, is an atypical neurological genetic condition that starts in infancy and progresses to death.

According to NIH, among the most prevalent degenerative brain disorders in young children is Canavan disease. Although it has been reported in other communities as well, Ashkenazi Jews are often affected. Nevertheless, there is insufficient information to determine the prevalence. Between 1:37 and 1:57 people are Ashkenazi carriers, which results in between 1:6000 and 1:14,000 prevalence rates.

While Canavan disease and Krabbe disease are distinct entities, both fall under the umbrella of leukodystrophies, sharing a commonality in causing progressive damage to the myelin sheath, albeit through different enzymatic deficiencies. It is linked to an enzyme deficit that causes the brain's white matter to disappear, which in turn causes faulty nerve signal transmission.

The most prevalent type, which typically presents with the most severe symptoms, is the neonatal variant. Most newborns seem healthy at first, but by two to six months, gross motor development deficiencies become evident. The baby might not be able to stand up by themselves, walk, turn over, or regulate their head motions. One prevalent characteristic is hypotonia, which is typically connected to macrocephaly. Most newborns have trouble eating and experience seizures.

It relates to a chromosome 17 gene locus. The aspartoacylase enzyme is encoded by the ASPA gene, which is mutated to cause it. Because of this mutation, the brain accumulates N-acetyl aspartic acid (NAA) and aspartoacylase is deficient. The deterioration of myelin in the phospholipid layer of axons, oligodendrocyte dysfunction, and ensuing spongiform alterations are thought to be caused by NAA. The most prevalent and severe kind is called infantile Canavan. Canavan disease infants frequently pass away in their early or teenage years. Juvenile Canavan is milder and less common. It doesn't seem that this kind of shortens lifespans.

Genetic counseling and inheritance of Canavan Disease-

As Canavan disease is an autosomal recessive disorder, two copies of a defective gene must exist for the disorder to manifest. The majority of individuals possess two fully functional genes that regulate the synthesis of the vital enzyme ASPA. A carrier, who has one functioning gene and one mutant gene, conveys the mutation to their offspring but does not exhibit any symptoms of the disease since one functioning gene is still adequate to manufacture the required enzyme. A child who receives two defective genes—one from each parent—is afflicted with the disease because they are unable to manufacture the enzyme.

When two carriers get conceived together, there is a one in four chance that the kid will be born with both genes carrying the mutation, which prevents the production of the enzyme and causes the condition. A child has a two-in-four probability of inheriting only one altered gene (carrier status) and a one-in-four chance of having two healthy genes and not being a carrier or suffering from the disease.

Sign & Symptoms

Every case of Canavan illness is different in terms of symptoms and course. Early symptoms of the disease typically appear between the ages of three and six months. These include substantially reduced muscular tone (hypotonia), an excessively large head (macrocephaly), and exceedingly poor head control, which causes "floppiness." Babies that are affected may exhibit overall irritability, lethargy, or lack of response (apathy). Dysphagia is a condition that certain babies may have that makes feeding challenging.

Most affected infants never walk independently, and they also exhibit delays in meeting developmental milestones like sitting and standing without assistance. Infancy also brings with it the progressive loss of skills involving the synchronization of mental and physical activity (psychomotor regression) and mental retardation. Most impacted newborns do acquire the ability to laugh, grin, raise their heads, and socialize.

Seizures, sleep disorders, feeding issues, blindness, nasal regurgitation, reflux—a condition in which stomach acid escapes the stomach and re-enters the esophagus—and optic atrophy—the weakening of the nerves in the eyes that carry signals from the retina, the nerve-rich membrane lining the eyes, to the brain—are among the other symptoms that children with Canavan disease may experience. Reduced visual response may result from optic atrophy. Although hearing is usually unaffected, hearing loss can happen.

Seizures, sleep disorders, feeding issues, nasal regurgitation, reflux—a condition in which stomach acid escapes the stomach and re-enters the esophagus—and optic atrophy—the weakening of the nerves in the eyes that carry signals from the retina, the nerve-rich membrane lining the eyes, to the brain—are among the other symptoms that children with Canavan disease may experience. Reduced visual response may result from optic atrophy. Although hearing is usually unaffected, hearing loss can happen.

Diagnostic Analysis

Laboratory Test

• Urine/blood/cerebrospinal fluid test: Urine NAA levels that are increased confirm the diagnosis of aspartoacylase deficiency in symptomatic neonates with comparable clinical characteristics and neuroimaging results. NAA levels in urine might become up to 200 times higher than the reference range. For measurement, mass spectrometry or gas chromatography are used. Moreover, elevated NAA levels have been found in the blood and CSF (cerebrospinal fluid).
• Cultured fibroblast: A lack of the enzyme aspartoacylase is found in some skin-derived connective tissue cells known as cultured fibroblast. Additionally, aspartoacylase activity are lacking in white blood cells.

Imaging test

• CT Scan: The white matter's edematous sponginess distinguishes it from the comparatively undamaged gray matter by producing a distinctively low radiographic attenuation on CT. The clinical stage may also influence the presence of megalencephaly.
• MR Spectroscopy: Megalencephaly, or a comparatively bigger brain, is one of the characteristics of an MRI. Usually, there is a diffuse bilateral involvement of the white matter. Subcortical U-fibers are typically involved early in the course of the disease, in contrast to other leukodystrophies. T2 displays a strong signal in the white matter, whereas T1 displays a weak signal. Post-contrast enhancement is absent. Significantly higher NAA levels and an elevated NAA:creatine ratio is revealed by MR spectroscopy.

Diagnostic Market Players

Treatment Analysis

For Canavan disease, there isn't a disease-modifying medication available yet. Infection treatment, respiratory protection, seizure avoidance, contracture risk reduction, nutrition and hydration maintenance, and prevention are the goals of management.

• Gastrostomy Tube: For those with dysphagia, a feeding gastrostomy tube is usually utilized to ensure proper nutrition and hydration. The patient's lack of sound reflexes makes a gastrostomy tube an additional safety measure against aspiration.
• Medication: Treatment for symptoms involves using prescription medicine, such as common antiepileptic medications, to control seizures. One treatment option for spasticity is botulinum toxin injections.
• Physical Therapy: The risk of contractures and ulcers is decreased with the use of physical therapy and positional modifications. In addition, they aid in bettering the patient's posture while sitting.
• Assistive devices: Assistive devices are equipment that improves mobility, communicates, and improves quality of life.

Treatment Market Players

Recent Development

• In April 2023, the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) granted Myrtelle innovative licensing and access pathway (ILAP) status for its gene therapy candidate, rAAV-Olig001-ASPA, which is intended to treat Canavan disease.
• In March 2022, The FDA has granted Fast Track, Rare Pediatric Disease (RPD), and Orphan Drug designations for Myrtelle Inc.'s lead clinical-stage gene therapy, rAAV-Olig001-ASPA, to be used in the treatment of patients with Canavan Disease (CD). Myrtelle Inc. is a clinical stage gene therapy company that focuses on developing transformative treatments for neurodegenerative diseases.

Clinical Trail Assessment

The DiseaseLandscape Insights consultancy firm provides valuable support in future market trends on the development of new pharmaceutical products. This support helps to streamline the planning and execution of clinical trials of novel medications and treatments, implement effective patient recruitment strategies, ensure regulatory compliance, and increase the likelihood of successful trial outcomes.

The below table gives information about currently ongoing clinical trials, including study titles and respective stages:

Conclusion:

DiseaseLandscape Insights (DLI) helps companies build and run effective strategies to prevent and control Canavan disease epidemics. Furthermore, as awareness and anticipated epidemics grow, there is a growing demand for diagnostic tools, clinical evaluations, and novel therapeutics.

Major players involved in the production of medicinal items might benefit from the information and experience provided by DiseaseLandscape Insights. The assistance provided by DLI facilitates patient recruitment strategies, regulatory compliance, and the planning and execution of clinical trials for novel medications and pharmaceuticals.

This ultimately motivates the leaders to conduct qualitative research, investigate manufacturing companies, and find out about raw material sources. All industry participants gain a stronger foothold in Canavan Disease and keep one step ahead with the help of DiseaseLandscape Insights.