ALS (SOD1)

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder that results in progressive muscular paralysis.

In North America, about 5 out of every 100,000 people have ALS, while 2 out of every 100,000 people develop it each year; in Europe, these numbers are 6 and 2, respectively.^[1] The rates can vary significantly by country and geographic region. ALS is more common in men than in women, and typically affects people between the ages of 55 and 75. After symptoms develop, most people live from 2 to 5 years.^[2]

In about 90% of ALS cases, there is no family history or genetic cause. This is called sporadic ALS. The other 5 to 10% of cases are known as familial ALS (FALS), where there is a known family history of the disease. Both types of ALS look similar in terms of symptoms.

Around 20% of FALS cases are due to changes in the SOD1 gene. These changes cause the gene to misfold and become toxic to nerve cells, leading to their damage. However, ALS can also occur due to new genetic changes in people with no family history of the disease.

uniQure’s investigational gene therapy candidate, AMT-162 uses a [AK1] virus to deliver a micro RNA (miRNA) molecule that has been designed to knock down the activity of the SOD1 gene. The goal of the clinical trial is to determine if AMT-162 can slow or halt ALS progression in individuals with SOD1 mutations.

There have been nearly 30 years of research linking the SOD1 gene mutation to ALS. Early preclinical studies in mice with ALS showed that administration of constructs similar to [AK2] AMT-162 improved survival and motor function in these animals. Additionally, testing in non-human primates showed that administration of AMT-162 resulted in reduced SOD1 levels in spinal cord nerve cells at the doses planned for human trials.^[3]

The U.S. Food and Drug Administration (FDA) has approved the initiation [AK3] for the clinical trial of AMT-162 to begin, and has granted Orphan Drug and Fast Track designations.

uniQure is currently conducting a Phase I/II clinical trial of AMT-162 called EPISOD1 in the United States, which is investigating the safety, tolerability and exploratory efficacy of AMT-162 in individuals with SOD1 related ALS.We believe AMT-162 may represent an important potential treatment option for people with this devastating disease.