A little web browsing shows there are at least 4 genes suspected of having a causal role in ALS: SOD1, DPP6, also see this and this, TDP43, and FUS/TLS (Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis, Science 323(1205) Feb 27 2009). You could have these 4 genes sequenced.
I’m suspicious of the DPP6 study, because they were studying non-hereditary ALS. How do they find a gene for a nonhereditary disease? Note that the third link above for DPP6 is to a study refuting its connection to ALS.
The sporadic form is IMHO likely not caused by gene mutations; otherwise, it would be familial.
All types of ALS AFAIK are associated with misfolded proteins accumulating in the cytoplasm of peripheral neurons. If a SOD1 mutation is at fault (20% of familial cases), then gene therapy adding a functional SOD1 protein was found not to help, likely because the mutated protein is still present and producing misfolded proteins. You could try to destroy the mutated SOD1 mRNA transcripts with RNAi (see this article on the first successful use of RNAi in peripheral neurons. Blocking the mutated SOD1 without adding a functional SOD1 causes death in mice. Therefore, you would need to sequence your SOD1 gene, find the mutation, design an siRNA matching that mutated mRNA but not the functional gene, and use gene therapy to provide a functional SOD1 gene. DNA binding is not specific enough to create an siRNA that can bind to the mRNA of a single-base-pair mutant but not the wild type; therefore, you might need to target the 3′ UTR of the mutant gene, and provide a different 3′ UTR in the gene therapy vector.
It would help if you could tell whether a particular protein is being misfolded and accumulating, and identify it. I don’t know how to do that.
If you can’t get a hold of papers behind a paywall, send me a list of up to a dozen citations, and I’ll try to get them for you.
Good call, at least in the sense that becoming expert on the relevant science of the disease also seems like the right thing to do in this situation, to be able to find short cuts the moment they become available.
A little web browsing shows there are at least 4 genes suspected of having a causal role in ALS: SOD1, DPP6, also see this and this, TDP43, and FUS/TLS (Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis, Science 323(1205) Feb 27 2009). You could have these 4 genes sequenced.
I’m suspicious of the DPP6 study, because they were studying non-hereditary ALS. How do they find a gene for a nonhereditary disease? Note that the third link above for DPP6 is to a study refuting its connection to ALS.
The sporadic form is IMHO likely not caused by gene mutations; otherwise, it would be familial.
All types of ALS AFAIK are associated with misfolded proteins accumulating in the cytoplasm of peripheral neurons. If a SOD1 mutation is at fault (20% of familial cases), then gene therapy adding a functional SOD1 protein was found not to help, likely because the mutated protein is still present and producing misfolded proteins. You could try to destroy the mutated SOD1 mRNA transcripts with RNAi (see this article on the first successful use of RNAi in peripheral neurons. Blocking the mutated SOD1 without adding a functional SOD1 causes death in mice. Therefore, you would need to sequence your SOD1 gene, find the mutation, design an siRNA matching that mutated mRNA but not the functional gene, and use gene therapy to provide a functional SOD1 gene. DNA binding is not specific enough to create an siRNA that can bind to the mRNA of a single-base-pair mutant but not the wild type; therefore, you might need to target the 3′ UTR of the mutant gene, and provide a different 3′ UTR in the gene therapy vector.
It would help if you could tell whether a particular protein is being misfolded and accumulating, and identify it. I don’t know how to do that.
If you can’t get a hold of papers behind a paywall, send me a list of up to a dozen citations, and I’ll try to get them for you.
Good call, at least in the sense that becoming expert on the relevant science of the disease also seems like the right thing to do in this situation, to be able to find short cuts the moment they become available.