KIDNEY DISEASE
Autosomal dominant MUC1 kidney disease (MKD, also known as ADTKD-MUC1, and formerly called MCKD1) is a rare hereditary renal disease that ultimately requires dialysis or kidney transplantation for patients. For decades, scientists had known the genetic “neighborhood” of the mutation causing MKD, a 2-million-base region on chromosome 1, but the specific mutation had remained elusive. But through the application of genetic sequencing technology and analysis methods, SIGMA researchers were able to identify a single disease-causing mutation lying in a “blind spot” of modern sequencing techniques. This discovery makes it possible to screen for the disease, and opens the door for potential new therapeutic approaches.
As part of this effort to target MKD, SIGMA scientists have launched a full-scale chemical biology program aimed at developing novel drug leads for treating the disease.
SIGMA
In 2010, the Carlos Slim Foundation and the Broad Institute came together to launch the Carlos Slim Center for Health Research at the Broad Institute. This unprecedented partnership aims to ensure that Latin Americans benefit from the genomic revolution by:
1. Promoting wider access to genomic medicine in Mexico and Latin America by supporting discovery programs that focus on health problems with particular relevance to the region, and leverage its unique population genetics.
2. Enhancing genomic research capacity in Mexico through training of scientists and encouraging the development of genomic diagnostics and therapeutics in Latin America.
That same year, with the contribution of $65 million from the Carlos Slim Foundation, the center launched the inaugural phase of the Slim Initiative in Genomic Medicine for the Americas (SIGMA). In this 3-year phase, Broad scientists worked closely with Mexican colleagues from 17 academic and research institutions led by the Mexican National Institute of Genomic Medicine, to systematically identify genes underlying cancer, diabetes and kidney disease, and to build capacity in Mexico in genomic medicine.
In 2013, in order to build on the project’s initial success, the Carlos Slim Center for Health Research launched the second phase of the collaboration, known as SIGMA II, with an additional contribution of $74.1 million over three years from the Carlos Slim Foundation.
SIGMA II will leverage the genetic discoveries from the first phase of the project, with a focus on translating these discoveries into clinical impact. This will include the development of diagnostic tools for breast cancer and diabetes, completing the genetic analysis of these diseases, creating therapeutic “roadmaps” to guide the development of new treatments, and the launching of a full-scale effort to target MCKD1. In addition, SIGMA II will continue to work on building scientific capacity in the US and Mexico.
In 2015 support from the Carlos Slim Foundation helped Broad Institute build the Type 2 Diabetes Genetics Knowledge Portal, developed by a team of scientists and software engineers at Broad, the University of Michigan, Oxford University, and other collaborators including the National Institutes of Health. The Portal is designed to help dramatically expand the number of researchers who can use human genetic data to study type 2 diabetes.
METABOLIC DISORDERS
LIPOTOXICITY
PROTEIN MISFOLDING