Lead programs
We are developing potentially transformational therapies for conditions for which there are currently few or no treatment options. These include lead programs for Duchenne muscular dystrophy, Huntington’s disease, and alpha-1 antitrypsin deficiency.
-
Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a fatal, X-linked genetic neuromuscular disorder that leads to progressive, irreversible loss of muscle function, including the heart and lungs.
DMD is a serious genetic disease affecting boys and a few girls worldwide; it is ultimately fatal.
Duchenne muscular dystrophy (DMD) is a fatal, X-linked genetic neuromuscular disorder that leads to progressive, irreversible loss of muscle function, including the heart and lungs.
DMD is a serious genetic disease affecting boys and a few girls worldwide; it is ultimately fatal.
affects~1/5,000
newborns around
the world~20K
new cases of DMD
annually worldwideThe cause of DMD
DMD is a genetic disease caused by a mutation in the dystrophin gene that prevents the production of dystrophin protein, a critical component of healthy muscle function. In skeletal and cardiac muscles, the dystrophin protein is part of a protein complex called the dystrophin-associated protein complex that acts as an anchor, connecting each muscle cell’s structural framework with the lattice of proteins and other molecules outside the cell through the muscle cell membrane. The dystrophin-associated protein complex protects the muscle from injury during contraction and relaxation. Without dystrophin protein, muscle tissue is replaced by fat cells and muscles deteriorate over time.
Our approach
Our approach focuses on exon skipping, a mechanism that may allow for the production of truncated (or shortened) functional dystrophin protein. Specifically, we have developed an investigational oligonucleotide therapeutic designed to skip exon 53 and restore the mRNA reading frame. This candidate incorporates Wave’s proprietary PN chemistry, which has been shown clinically and preclinically to improve pharmacological properties of exon skipping oligonucleotides.
-
Huntington’s disease
Huntington’s disease (HD) is a devastating autosomal dominant disorder that deeply impacts both patients and their loved ones.
Causing nerve cells in the brain to deteriorate over time, HD is characterized by cognitive decline, psychiatric illness and chorea. It is ultimately fatal and currently has no cure.
Huntington’s disease (HD) is a devastating autosomal dominant disorder that deeply impacts both patients and their loved ones.
Causing nerve cells in the brain to deteriorate over time, HD is characterized by cognitive decline, psychiatric illness and chorea. It is ultimately fatal and currently has no cure.
~30K
people in the US are estimated to be positive for HD and exhibiting symptoms
~200K
people in the US
are estimated to be at risk
of developing the conditionThe cause of HD
HD is a genetic disease caused by a mutation in the huntingtin (HTT) gene, which is believed to be critical for neuronal development. Specifically, an expanded section within the gene (CAG triplet repeat) results in production of an expanded huntingtin protein (mHTT). Accumulation of mHTT causes progressive loss of neurons in the brain, and can lead to neuronal cell death, causing motor, cognitive and psychiatric disability.
People with HD still possess wild-type (healthy) HTT protein, the suppression of which may have detrimental long-term consequences. Absence of healthy huntingtin protein has been shown to be embryonic lethal.
Our approach
Our program targets a specific single nucleotide polymorphism (SNP3) within the huntingtin gene. SNPs are naturally occurring variations within a given genetic sequence. In certain instances, SNPs can be used to distinguish between two related copies of a gene, where only one is responsible for causing production of a defective protein that causes disease. It has been shown that by targeting mHTT SNP3, the production of disease-causing proteins associated with HD can be reduced. This has the potential to provide treatment for up to 40% of people with HD.
