Research in tauopathies and frontotemporal lobar degeneration got two funding injections this month. The first is a newly established prize for tauopathy research, called the Rainwater Prize Program. Funders announced that $400,000 will go to Michel Goedert, Medical Research Council Laboratory of Molecular Biology in Cambridge, England, U.K., and Patrick Hsu, University of California, Berkeley, for their contributions to research in neurodegenerative disease. A much bigger boost comes in the form of a $63 million grant from the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). The grant funds a new consortium that combines two established NIH-funded studies, the Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS).
- $63 million NIH grant funds consortium for frontotemporal lobar degeneration.
- $250K prize goes to Michel Goedert for body of work in tauopathies.
- $150K goes to Patrick Hsu for advances in CRISPR-Cas9 editing.
The Rainwater Prize Program comes out of the Tau Consortium, a research program supported by the Rainwater Charitable Foundation. Richard Rainwater, an investor and philanthropist from Fort Worth, Texas, died in 2015 with progressive supranuclear palsy. Upon his diagnosis, he founded the consortium, which will now fund a series of four prizes for research and breakthroughs in tauopathies. The top two prizes have not been awarded yet, as $2 million to $10 million will go to an investigator or team of researchers whose work leads to breakthrough treatments for PSP. Up to $2 million will go to scientists whose work leads to treatments for tauopathies more generally. PSP is one of many tauopathies, as is Alzheimer’s disease.
Until then, the program will award prizes each year that recognize researchers whose work has advanced the field of neurodegeneration, especially tau-related disease. This year’s prizes will be presented in a ceremony at the Tau2020 Global Conference, to be held in Washington, D.C., on February 12 and 13. Goedert will receive $250,000 for Outstanding Innovation in Neurodegenerative Research. He discovered that tau is a critical component of the toxic intracellular filaments in Alzheimer’s disease, and did research on how the protein assembles into insoluble aggregates (Goedert et al., 1988; Goedert et al., 1996). He went on to find one of the first MAPT mutations that causes frontotemporal dementia, then created the P301S tau mouse model that is used widely in tauopathy research (Spillantini et al., 1998; Allen et al., 2002). The selection committee also recognized Goedert’s extensive efforts to mentor young researchers and share resources with labs all over the world.
Hsu earned the award for Innovative Early Career Scientist for his foundational work on CRISPR-Cas9, a technology that lets researchers alter DNA or RNA with more precision than was possible before. His lab discovered and developed CRISPR systems that edit RNA, which he used to reverse abnormal tau mRNA splicing in neurons from FTD patients (Mar 2018 news on Konermann et al., 2018).
A different, massive effort to support FTLD research comes from the NIH, which will fund an integrated consortium called the ARTFL–LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) research consortium. LEFFTDS focuses on genetic forms of FTD, while ARTFL includes patients both with and without known genetic mutations (Nov 2014 news; Dec 2018 news). The ALLFTD program will formally merge the ARTFL and LEFFTDS studies under one umbrella. It aims are to prepare for clinical trials by finding better biomarkers to identify, monitor, and forecast disease progression, as well as build trial-ready cohorts. The grant, to be distributed over five years, will fund infrastructure changes that will help improve data collection, storage, and sharing with research teams worldwide.—Gwyneth Dickey Zakaib
Research Models Citations
- New RNA CRISPR Tool Normalizes Tau Splicing
- Meet the Artful Leftie: NIH Jump-Starts U.S.-Canadian FTLD Cohorts
- Natural History Studies Provide Foundation for FTD Research
- Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4051-5. PubMed.
- Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith MJ, Crowther RA. Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature. 1996 Oct 10;383(6600):550-3. PubMed.
- Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7737-41. PubMed.
- Allen B, Ingram E, Takao M, Smith MJ, Jakes R, Virdee K, Yoshida H, Holzer M, Craxton M, Emson PC, Atzori C, Migheli A, Crowther RA, Ghetti B, Spillantini MG, Goedert M. Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J Neurosci. 2002 Nov 1;22(21):9340-51. PubMed.
- Konermann S, Lotfy P, Brideau NJ, Oki J, Shokhirev MN, Hsu PD. Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors. Cell. 2018 Apr 19;173(3):665-676.e14. Epub 2018 Mar 15 PubMed.