Neuromuscular Diseases

There are a large number of neuromuscular diseases and together with  Leiden University Medical Center and UU QVQ has done work in various areas within neuromuscular diseases. An extensive program on OPMD has delivered proof that VHH can be used as intrabodies to prevent aggregation of unwanted proteins which can lead to muscular diseases. This knowledge has been used in other programs for Alzheimer’s disease and Huntington, among others.

Herewith 2 examples of the VHH related to neuromuscular diseases. The first example is the selection of VHH against enzymes that are important in the formation of Amyloidβ.

Figure 1: Pathological processing pathway of APP.

Currently QVQ and LUMC, supported by the Dutch FSHD Foundation is in a process to select VHH against the main driver of FSHD, DUX4 but also against a number of proteins related to the disease. These proteins are often called Foot Print Proteins and are present in the muscle cells and on their surfaces. Whereas the VHH selected against the intracellular proteins are currently screened on blocking DUX 4 itself [See Fig 2 ] or the detrimental effect of the DUX4 expression on other processes in the cell. FPP present on the surface of these muscle cells can be used for imaging.