Huntington’s Disease is a rare inherited neurodegenerative disorder that causes the progressive breakdown of nerve cells. Advantx‘s candidate ADV368 has been precisely designed to bind Sigma-1 and Sigma-2 receptors to improve motor neurons survival and muscle function.

Neurons in Huntington's disease

Huntington's Disease

Huntington’s disease (HD) is an inherited neurodegenerative disease characterized by neuropsychiatric symptoms, movement disorders, and progressive cognitive impairment. It is caused by a mutation in the CAG repeat region of the HTT gene. The mutant huntingtin (mHTT) protein presents an expanded polyglutamine (polyQ) tract that confers the protein the tendency to misfold and form aggregates primarily in neurons. Misfolded mhtt interferes with normal cellular processes that result in neurodegeneration primarily affecting striatum, cerebral neocortex and sub-cortical white-matter but also other brain areas. The trigger event-driven is likely to occur many years before the first signs of neurodegeneration. Despite the single gene cause, a large number of downstream pathways are implicated in the disease pathogenesis including transcriptional dysregulation, decreased neurotrophic signaling, oxidative stress, unfolded protein response, protein degradation, glutamate-mediated excitotoxicity, mitochondrial fragmentation, reduction in ATP levels, and inflammation.
Sigma ligands reduce the size of Htt aggregates and protein misfolding, counteracting its effects by increasing cellular antioxidants, reducing the oxidative level, restraining inflammation, and promoting activity in macrophages, without changing mitochondrial Ca2+ concentration, also increasing the expression of neuroprotective factors, such as BDNF and DARPP32. Sigma ligands also inhibit the iron accumulation in neurons, by blocking the huntingtin interaction with the Amyloid precursor protein (APP), which also interferes with iron trafficking at the blood-brain barrier, contributing to synaptic defects and reduction in number, and decline in motor endurance.
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Potential market for Advantx candidate in Huntington's Disease


>100k people in US/EU/UK/JP

Treated Population

>100k patients

Market Size


Market Growth

est. 17.4% CAGR

data from Globaldata

Huntington's Disease and Amyotrophic Lateal Sclerosis, are two devastating diseases caused by an aggregation of misfolded proteins resulting in nerve failure and muscle atrophy


Huntington’s disease (HD) in contrast with other genetic disorders, has a monogenic cause, the CAG-repeat expansion in the first exon of the HTT gene encoding the huntingtin scafold protein, producing an expanded polyglutamine tract in the amino terminus. The length of the expanded CAG tract is related to age at disease onset, with longer repeats leading to earlier onset. Mutant huntingtin interferes with many cellular processes, specifically the ER stress and the unfolded response pathways.
Sigma proteins are intracellular chaperones that could prevent aggregation of Huntingtin and associated misfolded proteins by activating the unfolded protein response (UPR) reduced by ER stress.
Huntington’s disease symptoms can develop at any time, but they often first appear when people are in their 30s or 40s, and from the first symptoms to death usually span 15 to 30 years.
If the condition develops before age 20, it’s called juvenile-onset Huntington’s disease (JOHD) and disease progression in patients is faster and survival shorter compared to adult-onset, about 10 years.


Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease, is a progressive neurodegenerative disease that attacks cells in the brain and spinal cord needed to keep muscles moving, leading to muscle weakness and paralysis. Over time, complications appear with dysphagia and respiratory distress. Aberrant regulation of the mitochondria-associated membrane (MAM) is associated with sporadic cases of ALS. About 10% of ALS patients have inherited forms, while sporadic forms with no family history represent the majority of patients. Some mutations in familial cases are in SOD1 gene, in chromosome C9orf72, or in the TDP43, resulting in misfolding and accumulation of these proteins in the brain. Recent research has uncovered a SIGMAR1 (E102Q) gene mutation initially identified in juvenile ALS. Aggregation of σ1RE102Q-mCh also leads to dysregulation of calcium homeostasis and ER stress, ultimately resulting in cell death.
ALS prevalence is approximately 6 cases per 100 000, with an average age of onset currently at 55-60 years and the average survival from onset to death is 3-4 years.
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ADV368 HD is Advantx’s candidate for the treatment of Huntington’s Disease and Amyotrophic lateral sclerosis.