Development is under way of a blood test that may help doctors rule in or rule out a diagnosis of amyotrophic lateral sclerosis (ALS).
The test, being developed by Amorfix Life Sciences in Ontario, Canada, relies on the use of antibodies (immune-system proteins), which act as "molecular magnets" to detect and measure improperly folded SOD1 protein. Misfolded SOD1 is thought to play an important role in both the familial and sporadic forms of ALS.
If successful, such a test could speed up the diagnostic process and enable earlier treatment of the disease.
As reported in a Jan. 22, 2013 Amorfix press release, the new test is based on work by Neil Cashman, Amorfix chief scientific officer and company founder, which shows that misfolded SOD1 is present in the blood of people with ALS.
Cashman, also a clinical neurologist and neuroscientist at the Brain Research Centre, University of British Columbia in Vancouver, Canada, has long hypothesized that misfolded SOD1 molecules are tied to the spread of weakness in ALS.
His current work includes a focus on the development of misfolding-specific antibodies not only to detect improperly folded SOD1 (as they are being used in the blood test), but for a second purpose: to target and block the misfolded protein as a therapeutic strategy.
Mutations in the SOD1 gene, first identified as a cause of familial ALS in the early 1990s, result in the production of any number of varieties of improperly folded SOD1 protein.
(Note: Only about 5 percent of ALS is familial, where there is a history of ALS in more than one family member; the other 95 percent occurs sporadically without any family history of the disease.)
But recent evidence reported by Cashman shows that even normal SOD1 protein has a propensity to misfold, after which it induces misfolding in neighboring SOD1 protein molecules.
The propagation of misfolded SOD1 protein in the body appears to drive cell-to-cell and region-to-region spread of ALS in both the familial and sporadic forms of the disease.
In related news, Amorfix reported in a press release Nov. 7, 2012, that anti-SOD1 antibodies developed by the company are being used by Serge Przedborski, professor of neurology and pathology at Columbia University in New York, to investigate the ALS disease processes and progression.
Like Cashman, Przedborski is using the antibodies both to detect and to block proteins. He first is working to identify nervous system cells that generate misfolded SOD1 and determine the misfolded protein's toxic effects on motor neurons. Later, he plans to use the anti-SOD1 antibodies to block toxicity and protect motor neurons.
Amorfix also has licensed its antibody targets against misfolded SOD1 protein to multinational biotechnology company Biogen Idec for the development of antibody-based therapeutics, and to Pan Provincial Vaccine Enterprise (PREVENT) for the development of vaccines.
For more about SOD1 in ALS, see: