Silence ALS
Discovering Breakthroughs for Rare ALS Mutations
What is Silence ALS?
- Silence ALS is an initiative established in partnership with the n-Lorem Foundation to discover and develop personalized experimental antisense oligonucleotide (ASO) medicines for ALS patients with rare, disease-causing gene mutations.
- 10-15% of people diagnosed with ALS have an underlying genetic cause. Knowing the genetic cause of disease allows researchers the opportunity to develop a targeted treatment at the starting point.
- ASO medicines designed for relatively common genetic forms of ALS, including SOD1, C9orf72, and FUS, offer hope to the majority of ALS patients and families with these forms of the disease.
- Silence ALS will apply this promising gene-based therapeutic strategy to ALS patients with rare gene mutations, offering hope and the opportunity for benefit to these individuals and families.
- This program will lead to a greater understanding of the biology of disease common to all forms of ALS and related disorders like FTD.
FAQ
What is antisense oligonucleotide (ASO) therapy?
Antisense oligonucleotide (ASO) therapy is a type of treatment that uses small pieces of genetic material to target and modify specific genes in our bodies. It's a promising approach in medical research for treating genetic diseases.
Let's break it down into simpler terms:
- Genes: Our bodies are made up of trillions of cells, and each cell contains our entire genetic code, our genome. Our genome is comprised of over 20,000 genes. Genes, made up from our DNA sequence, are like instruction manuals that tell our cells how to make proteins, which are essential for our body's functioning. First the DNA sequence of the gene is transcribed into messenger RNA (mRNA). mRNA carries the instructions to the cellular machinery to create the correct protein.
- Genetic diseases: Sometimes, there are mistakes or abnormalities in the DNA spelling of our genes. These are referred to as “gene mutations”, “disease-causing variants” or “pathogenic variants”, and are the cause of genetic diseases. Roughly 10-15% of people with ALS have a genetic mutation that causes disease. Most ALS-associated gene mutations cause disease by creating an abnormal protein product instead of a normally functioning protein.
- Antisense oligonucleotides (ASOs): ASOs are tiny pieces of genetic material, usually made of a special type of molecule called RNA. They are designed to specifically bind to and target the mRNA of a specific gene. When ASOs are introduced into our body, they seek out the specific genes they are designed to target. Once they find their target gene, they bind to it and interfere with its normal activity.
- Treating genetic diseases: ASO therapy aims to correct the underlying genetic cause of a disease. By modifying the activity of specific genes, it can potentially restore normal functioning and alleviate the symptoms or slow down the progression of the disease.
Are you eligible to participate in Silence ALS?
To be eligible to participate in the Silence ALS program:
- You have a diagnosis of ALS.
- You have an ALS-causing gene mutation in one of the genes being pursued in Silence ALS. (Please reference below list.)
If you have further questions about genetics and ALS, please refer to the Genetics of ALS page. If you have not had genetic testing, or have questions about your test results, please reach out to your neurologist to discuss further.
To assess your eligibility, please fill out the Silence ALS Intake Form.
What genes are being pursued in Silence ALS?
Genes that are currently being pursued as part of the Silence ALS program include:
- ANXA11
- CHCHD10
- KIF5A
- PFN1
- TARDBP
- VAPB
- VCP
Other genes may be added to this list as the program grows, so please reach out if you have questions about other ALS-associated genes that may be amenable to ASO therapy.
Are there specific genes that are not eligible for Silence ALS?
Currently, the ALS-associated genes SOD1, C9orf72, and FUS are not being pursued as part of Silence ALS.
What if I am asymptomatic but have a rare ALS gene mutation in my family?
If there is a known ALS-associated gene mutation in your family or if you have a strong family history of ALS (two or more family members with ALS), we would be interested in speaking with you. You or your family may be eligible to partake in the Silence ALS program, or it may be more appropriate for you to participate in the PREVENT ALS research study.