Neurology Central

Monoclonal antibodies for broad-range treatment of neurodegenerative diseases

A research team led by Fernando Goni and Thomas Wisniewski at the Center for Cognitive Neurology at New York University Langone (NY, USA) have developed three types of IgM monoclonal antibodies (mAbs) that may offer promise for the treatment of a range of neurodegenerative diseases. The study, which sought to determine the binding specificity and capacity of the mAbs to target disease-causing toxic aggregates, was presented recently at the 2015 Alzheimer’s Association International Conference (Washington, DC, USA; 18–23 July 2015).

It is well established that neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and GSS (human prionosis) have a similar pathogenesis involving the misfolding of proteins within the brain. Such misfolding leads to the conversion of operational proteins into nonfunctioning toxic aggregates, culminating in neurological decline.

The antibodies developed were raised in mice against the common b-sheet structure found in the toxic oligomers of various neurodegenerative diseases including those found in Alzheimer’s, Parkinson’s and prion disease.

Previous studies by Goni and Wisniewski indicated that mAb treatment could be effective in preventing the formation of the hallmark plaques and tangles of Alzheimer’s and Parkinson’s disease and/or by preventing these aggregates spreading throughout the brain. The results also highlighted that mAbs reacted to the intermediate-state oligomeric proteins present in neurodegenerative diseases.

In the current study, the three mAbs were tested against monomeric, oligomeric and fibrillary aggregates of α-synuclein in mice models. The results indicated that all three mAbs had a binding specificity for the oligomeric forms of alpha-synuclein. The results were also confirmed in brain tissue samples from individuals with Parkinson’s and Alzheimer’s disease.

“There is a commonality underlying the misfolding in many neurodegenerative diseases and we are targeting it. We are confident this is the right strategy and our monoclonals are showing they are up to the task. There is potential for specific therapeutic agents for neurodegenerative diseases,” remarked Goni. Wisniewski also commented: “The importance of this concept is being increasingly recognized.”

The team’s next steps in the development of this approach towards a successful treatment for neurodegenerative diseases will be to extend the regimen to further animal studies, utilizing the mAb regimen both alone and in combination with other treatments. They then hope to move into human clinical trials.

With the incidence of Alzheimer’s disease and other dementias already reaching 47 million worldwide and expected to increase threefold by 2050, according to the Alzheimer’s Association, the discovery of an effective treatment is highly significant.

Sources: NYU Langone Medical Center press release via Newswise; Goni F et al. Monoclonal antibodies that recognize oligomeric tau and Aβ, also recognize pathological structures in Parkinson’s disease human brains. Abstract #5364. Presented at: Alzheimer’s Association International Conference. Washington, DC, USA, 18–23 July 2015.