We are building a leading CNS company based on our RNA modulating therapies
- Non Clinical
- RETT SYNDROME
- Not Disclosed
To learn more about our disease areas of focus
By employing antisense oligonucleotides as RNA modulating therapeutics, we aim to correct genetic mutations at the protein level without inducing permanent changes to the original DNA code.
Our approach is applicable to a broad range of genetic diseases. Dependent on the nature of the genetic mutation, different corrective mechanisms of action are employed.
A specific subset of neurogenetic diseases CAG denoted as triplet repeat expansion diseases is caused by trinucleotide repeat expansions, often affecting stretches of CAG repeats. VO659 has been designed to block the protein synthesis (translation) of transcripts containing such CAG repeats.
Spinocerebellar ataxia (SCA) are a group of rare, progressive hereditary genetic disorders that affects the cerebellum, brain stem and spinal cord. More than 30 types of SCAs have been identified to date (SCA1–SCA36), and the most common SCAs (types 1, 2, 3, 6 and 7) are caused by translated CAG trinucleotide repeat expansions that encode elongated polyglutamine (polyQ) stretches in the respective disease proteins. Presence of the elongated polyQ stretch confers pathogenic properties to the resulting protein through a dominant gain-of-function mechanism, resulting in degeneration of specific neuronal subpopulations that differ between the different SCA types. For SCA1 and SCA3 disease manifestation includes ataxia of gait, stance, and limbs, dysarthria, and oculomotor abnormalities. To date, there are no disease-modifying therapies.
VICO’s lead antisense oligonucleotide product is designed to suppress these mutant proteins and slow or halt disease progression. A major strength of VICO's approach is the broad applicability to different polyQ diseases and the preferential reduction of mutant relative to normal polyQ proteins. VICO is planning a first in human trial for SCA 1 and SCA 3 patients to commence in 2022.
Huntington’s disease (HD) is a rare hereditary neurodegenerative disorder with a progressive and fatal course characterized by movement disorders, cognitive impairment, dementia and psychiatric manifestations including depression and psychosis. The disease has a wide variation in onset age, with an average age at onset of mid adulthood. Prevalence is an estimated 4-10 per 100,000 population. Today there is still a significant unmet need in disease-modifying therapies for the treatment and management of HD, with drugs that can alleviate some of the movement and psychiatric symptoms, but no curative treatments available.
The disease causing mutation is the expansion of a CAG-trinucleotide repeat in the coding region of exon 1 of the HTT gene, which results in a mutant huntingtin protein with an elongated polyglutamine (polyQ) stretch at its N-terminus. This expanded polyglutamine stretch confers a toxic gain-of-function to mutant protein forms, ultimately resulting in selective death and dysfunction of specific neuronal subpopulations within the central nervous system. Besides a toxic gain-of-function of mutant huntingtin, loss of the functions of normal huntingtin likely also plays a role in pathological mechanisms of HD.
VICO’s lead antisense oligonucleotide product is designed to suppress these mutant proteins and slow or halt disease progression. A major strength of VICO's approach is the broad applicability to different polyQ diseases and the preferential reduction of mutant relative to normal polyQ proteins.
Rett syndrome (RTT) is a neurodevelopmental disorder affecting brain development, characterized by severe mental and physical disability. First symptoms include regression of early developmental milestones, such as speech and purposeful hand motions, followed by severe motor abnormalities, including respiration, and premature death, typically by age 40. Boys have an even more profound disease, usually succumbing before 2 years of age. It is estimated that approximately 1 in 10,000 – 15,000 girls each year are affected, and Rett Syndrome is only rarely seen in boys. There is no cure for RTT, treatment is directed at improving symptoms.
The underlying genetic defect is a mutation in the gene encoding the global transcriptional regulator, Methyl CpG Binding Protein 2 (MECP2), located on the X chromosome. MECP2 is a global transcriptional regulator and essential for normal nerve development and function and acts as one of the many biochemical switches that can either increase gene expression or direct other genes when to turn off and stop producing their own unique proteins. VICO's therapeutic strategy is based on antisense oligonucleotide-mediated RNA editing to repair mutant MECP2 and reverse symptoms.
Trinucleotide repeat disorders are a set of over 50 genetic disorders caused by trinucleotide repeat expansion, a mutation in which repeats of three nucleotides (trinucleotide repeats) increase in copy numbers until they cross a threshold above which they become unstable.
Some of the problems in trinucleotide repeat syndromes result from causing alterations in the coding region of the gene, while others are caused by altered gene regulation. In over half of these disorders, the repeated trinucleotide, or codon, is CAG. In a coding region, CAG codes for glutamine (Q), so CAG repeats result in a polyglutamine tract. These diseases are commonly referred to as polyglutamine (or polyQ) diseases.
Inheritance of almost all of the polyQ diseases follows an autosomal dominant pattern. This means that if a parent has a mutation in one of the genes, each child has a 50% (1 in 2) chance to inherit the same mutation. This can be explained by a dominant, toxic effect of the altered proteins containing the prolonged CAG repeat. Dependent on the actual protein altered, different sets of neuronal cells are adversely affected and degenerate, resulting in the differential disease phenotypes of the various polyQ diseases.
In general, the larger the expansion the faster the onset of disease, which indicates that length of the mutation largely determines the rate of the abnormal process leading to the manifestation of the disease.