Ludwig Cancer Center Scientist Wins $3 Million Breakthrough Prize for ALS Discovery

Ludwig Cancer Research scientist Don Cleveland has received a $3 million Breakthrough Prize for increasing science’s understanding of how an inherited form of amyotrophic lateral sclerosis develops.

His work focused on glia, cells that support the body’s production of a protein called myelin, which protects nerve cells. Deterioration of myelin leads to the nerve cell loss seen in ALS and other diseases. Abnormal glia functioning contributes to the degeneration.

Affiliated with the New York-based Ludwig center since 1995, Cleveland is now a professor of cellular and molecular medicine at the University of California, San Diego.

He has been a leader in neurodegenerative-disease research and therapy development for decades.

He pioneered antisense oligonucleotide therapy in animal models of ALS and Huntington’s disease, for example. This approach to treating genetic disorders works by inactivating disease-causing genes by targeting their mRNA molecules. The molecules are intermediate players in the production of protein.

Another of his discoveries was that a faulty version of the superoxide dismutase enzyme plays a key role in the development of inherited ALS, according to a press release.

Cleveland also discovered that abnormal versions of the tau protein help cause cognitive disorders such as Alzheimer’s disease.

In addition, he has helped develop gene silencing technology that has led to the development of  therapies for ALS, Huntington’s, and Alzheimer’s. The technology has also been used to treat Parkinson’s disease, chronic brain injury, and glioblastoma, the most common form of nervous system cancer.

Only 5 to 10 percent of people with ALS have an inherited form of the disease or a related condition known as frontotemporal dementia, or FTD, according to Genetics Home Reference. FTD is a progressive brain disorder that affects personality, behavior and language. Some people develop both conditions, so doctors diagnose them with ALS-FTD.

In rare cases, symptoms of ALS can appear in childhood or in the teens. When this happens, the disorder is known as juvenile ALS.

RNA, which plays numerous roles in a cell, is composed of building blocks similar to those in DNA. In RNA the blocks are called letters, and sometimes stretches of RNA contain repeats of the letters. This disrupts RNA’s normal activity and leads to it accumulating in cells, disrupting other cell operations.

Repeats of RNA sequencing that generate abnormal versions of the C9orf72 gene cause about a third of inherited ALS cases.