Researchers based at Washington University School of Medicine have created a genomic atlas of proteins found in the brain of Alzheimer’s disease patients and found new potential drug targets for treating Alzheimer’s, Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and stroke.
The team says they have analyzed existing drug databases and found 29 drugs, already approved by the FDA for other indications such as cancer, arthritis, glaucoma and epilepsy, that could be used to target these conditions. As these drugs have already undergone safety tests, it’s likely they could be on the market sooner than standard drugs should they be proven effective.
“Using Alzheimer’s disease samples, we’ve been able to identify new genes, druggable targets and FDA-approved compounds that interact with those targets to potentially slow or reverse the progress of Alzheimer’s,” said Carlos Cruchaga, a professor at Washington University School of Medicine and lead author on the study, in a press statement.
“The classic genetic studies of Alzheimer’s have attempted to correlate genetic mutations with disease, but we know that genes carry the instructions to build proteins and that diseases such as Alzheimer’s occur when those protein levels get too high or too low… To understand the biology of Alzheimer’s disease, we should look at proteins rather than only at genes.”
As described in the Nature Neuroscience paper about the research, the researchers first generated an atlas of protein levels relevant to neurological disorders in the brain, cerebrospinal fluid and plasma in 1537 participants both with and without Alzheimer’s disease.
Overall, 713, 931, and 1079 proteins from cerebrospinal fluid, plasma, and brain samples, were used in the analysis. The researchers then carried out a genome wide association study of more than 14 million genetic variants to assess which proteins could be linked to disease. They found 274 proteins linked to disease in cerebrospinal fluid, 127 in blood plasma and 32 in brain tissue.
Some proteins previously linked with Alzheimer’s were detected, but other associations were new. To assess if any of the disease-related proteins matched drug targets of already approved drugs, the researchers scanned their results through approved drug databases.
They identified 15 that could have potential to treat Alzheimer’s, seven Parkinson’s, six stroke, and one ALS. For example, the gene CD33 and its protein were linked to Alzheimer’s. CD33 is the target an antibody drug used to treat acute myeloid leukemia. Similarly, the IDUA gene was associated with Parkinson’s. It’s associated protein functions to breakdown glycosaminoglycans in the lysosome and chondroitin sulfate, used in the treatment of osteoarthritis, was identified as a possible drug candidate.
“They are FDA-approved, and all of the safety data on the drugs is available,” said Cruchaga. “With what is already known about the safety of these drugs, we may be able to jump directly to clinical trials.”
The team are now using machine learning techniques on their findings to try to better pinpoint the proteins that cause damage in Alzheimer’s disease.
