The NeuroLINCS Center is an NIH-funded collaborative effort between various research groups with expertise in iPSC technology, disease modeling, OMICS methods, and computational biology. The participating research groups are from the University of California- Irvine, Cedars Sinai, the Gladstone Institute, MIT, and Johns Hopkins University. Together, the NeuroLINCS data and signature generation center studies human brain cells derived from patient-derived iPS cells to understand the causes of neurological disease and to develop new therapies.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition characterized by loss of motor neurons in the brain and spinal cord. It is also commonly known as “Lou Gehrig’s Disease” in the USA and “motor neuron disease” in Europe and the rest of the world. ALS presents clinically as muscle wasting with stiffness and spasticity from loss of motor neurons in the spinal cord. New research indicates that a substantial number of ALS patients also have mild to moderate dementia, and pathological studies document neurodegeneration and abnormal astroglial/oligodendroglial functions throughput the brain and spinal cord.
ALS is largely sporadic, but several genes, including SOD1, C9orf72 and TDP43 have been identified in a subset of patients. Clinically sporadic and familial ALS appear similar. The C9orf72 mutation is unusual in several regards: it is a hexanucleotide repeat expansion of the first intron of the gene and the expansion may repeat thousands of times; the mutation is found in ~40% of familial ALS – but also in 8-10% of apparent sporadic disease as well. Finally, it is equally common in frontotemporal dementia- both in the familial and sporadic forms. ALS patients with severe frontotemporal dementia most often carry the C9orf72 mutation. Spinal muscular atrophy (SMA) is a recessively inherited pediatric neuromuscular disease characterized by degeneration of spinal motor neurons.
Discovering a cure for these fast-progressing diseases has remained elusive as only one FDA approved treatment exists for ALS, a drug called Riluzole, which prolongs a patient’s life modestly by about one year. No treatment exists for SMA. Clearly, more substantive therapeutic options are required to improve the survival and quality of life for these patients. The scientific community agrees that the search for new therapeutics for these debilitating motor neuron diseases requires highly-innovative strategies, including generating and optimizing a large database of patient-specific cellular (neuronal for ALS) data, with the ultimate goal being that these datasets will further encourage and stimulate “out-of-the-box ideas” in the broader neurodegenerative disease research field.