IXA has awarded the first APCA grants to two AMC projects, “Applying histatin 1 to improve integration of dental implants” by Jan Stap and Irene van Dijk and “Identification of compounds that interfere with protein aggregation in Huntington’s Disease” by Eric Reits.
This APCA grant offers the opportunity to carry out conceptual, technical, social and/or economic feasibility studies on their concepts, inventions or ideas. To further develop an innovative idea or an invention, it may be necessary to test whether the idea can be made ready for the market. A feasibility test is the way to do this (also called “proof of concept” studies). The APCA is a financial facility provided by the City of Amsterdam, in collaboration with the IXA institutes, (i.e. VU, VUmc, AMC, UvA and HvA) and NKI.
Applying histatin 1 to improve integration of dental implants
When a dental implant is placed, the soft tissue and bone cells that surround it have to adhere to the implant and to each other in order to fix the implant in place and to create a barrier against infections.
Histatin 1 is a peptide (small protein) from human saliva which promotes cell-substrate attachment and cell-cell adhesion. Jan Stap and Irene van Dijk found that histatin 1 can be used to improve the attachment of soft tissue and bone cells to dental implant material. Histatin 1 can be especially useful to promote rapid soft tissue integration which is important to seal off the lower part of an implant, thereby preventing infection, and helps to accomplish improved aesthetics. Moreover, histatin 1 may shorten the period between placing the implant and loading it with a replacement tooth. Histatin 1 may also facilitate more rapid re-attachment of the bone cells to the implant after bone loss due to infection. An advantage of the method developed by Jan Stap and Irene van Dijk is that it can be combined with existing techniques and therefore an additive effect may be achieved.
The APCA funding will be used to test the adhesion-promoting effect of Histatin 1 on cells plated on titanium. Moreover, in vitro experiments will be done to determine the concentration and frequency of dosing in the in vivo experiments. These are important tests to prepare for the next step of an in vivo experiment, which we want to execute with a commercial partner.
Identification of compounds that interfere with protein aggregation in Huntington’s Disease
Most neurodegenerative disorders such as Alzheimer, Parkinson and Huntington are caused by aggregating huntington proteins in the brain. Huntington’s disease is caused by a mutation in the disease-related huntington protein, leading to its aggregation and neurodegeneration. Accelerating the degradation of mutant huntingtin to prevent aggregation would be a direct therapeutic strategy for this deadly disease for which there is no cure. Eric Reits and his team have developed a unique assay to visualise mutant huntingtin aggregation in neuronal cells using fluorescently-labelled mutant huntingtin protein fragments. Currently a large screen with a library of 300.000 small molecule compounds is ongoing in collaboration with CD3 (Leuven) to select compounds that improve mutant huntingtin degradation, and form the base for a potential medicine for Huntington.
The APCA funding will make it possible to attract a technician to the research team to validate effective compounds selected in the screen in various Huntington disease models for specificity and mechanism of action. Ultimately, the most promising compound may be developed into a drug for treatment of Huntington’s disease.
How does the APCA loan work?
An application to the APCA fund may not exceed € 45,000, of which 50% is a loan and 50% needs to be matched (cash or in kind) by the applicant. At least 75% of the cost of the POC study should then be spent at one of the affiliated Amsterdam knowledge institutes. The contribution from the Fund is a loan with soft conditions.
APCA fund is made possible by the City of Amsterdam.
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