A Mayo Clinic research team that recently announced a breakthrough in ways to research amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and an increasingly frequent type of dementia has won a patent on a powerful new genetic test for those neurodegenerative diseases.
The U.S. Patent Office in late September approved an application by Mayo for a novel immunoassay targeting ALS and frontotemporal dementia (FTD), invented by members of its Neurodegenerative Diseases Lab, led by Leonard Petrucelli, chairman of the clinic’s neurology department in Jacksonville, Florida.
More than 30,000 Americans live with ALS, a condition that destroys motor neuron cells that control essential muscle activity such as speaking, walking, breathing and swallowing. Meanwhile, FTD has become the most common form of early onset dementia after Alzheimer’s disease, characterized by changes in personality, behavior and language due to loss of neurons in the brain’s frontal lobe. It is now thought to account for up to 10 to 15 percent of all dementia cases.
Petrucelli and his Mayo colleagues made news last year with the announcement that they had developed a mouse model that mimics the human neuropathological and behavioral features associated with the most common genetic form of ALS and FTD, which are both caused by a mutation in the C9ORF72 gene.
Their mouse model has been hailed as a breakthrough because the mice exhibit human pathologies such as hyperactivity, anxiety, antisocial behavior and motor deficits. The brains of the specially bred mice have key hallmarks of the disorders, including toxic clusters of ribonucleic acids (RNA) and TDP-43, a protein that has long been known to go awry in the majority of ALS and FTD cases.
TDP-43 has also been found in Alzheimer’s disease patients and in people who experience head injuries or repeated concussions.
The substance is found within abnormal “foci,” or clumps, of toxic RNA generated by the mutated C9ORF72 gene typical in disease sufferers. What links the foci and TDP-43 remains unclear, but with the development of a mouse model, researchers now have a way to find out.
Mayo says that not only will the new mouse model be useful for testing new drugs, but that the study findings also suggest that a drug now used to alleviate the toxicity associated with foci can prevent TDP-43 pathology as well.
Petrucelli’s lab is working to identify compounds that bind to the toxic RNA before it can form into clumps. The hope is that by treating the RNA and TDP-43 with drugs, doctors can prevent the formation of foci in brain cells, thus combating the disease symptoms that ALS patients suffer.
Meanwhile, Petrocelli, fellow Mayo Jacksonville professor Tania Gendron and Boston University researcher Peter Ash since 2014 have had a patent pending on a new kind of powerful and highly sensitive molecular test, or immunoassay, to diagnose properties of the mutated C9ORF72 gene. On September 20, their application was granted by the patent office.
The inventors claim it as a significant step forward because it can quickly and efficiently determine from biological samples if a patient is showing elevated levels of suspect proteins without the need for costly and time-consuming nucleic acid amplification tests, which have been criticized for requiring expensive instrumentation and dedicated laboratory spaces.
One key aspect of the new immunoassay, they say, is that is can also differentiate between indications of ALS and FTD in samples.
The global immunoassay market, which includes all uses of bioengineered antibodies to track down and measure proteins or other molecules in the human body, is expected by some estimates to grow to nearly $25 billion by 2019, thanks mainly to an aging population and the rising number of chronic diseases such as ALS and FTD.