ALS (amyotrophic lateral sclerosis) is a progressive and fatal neuromuscular disease for which no cure has yet been found. Researchers have however managed to successfully extend the lifespan of mice with ALS.
“ALS causes motor neurons to deteriorate and die. Existing drugs have no effect on the disease, and survival after the onset of ALS is approximately 3–5 years,” says Professor Mart Saarma. Saarma heads an international research consortium that is exploring the effect of the conserved dopamine neurotrophic factor (CDNF) on ALS. Neurotrophic factors are proteins that support and regulate the survival and developmental growth of neurons.
The Finnish parties of the Saarma-led consortium are neuropharmacologist Merja Voutilainen and the team of neuroimmunologist Pentti Tienari.
The consortium has secured funding from E-Rare, the ERA-NET for Research Programmes on Rare Diseases. ERA-NET is a funding instrument of the EU Framework Programme that contributes to the promotion of cooperation between national research programmes and research funding agencies with a view to promoting research in Europe. The Academy of Finland’s Research Council for Health co-funded the E-Rare call in 2017, from which Saarma’s and Tienari’s consortia won funding.
Professor Mart Saarma and Academy Research Fellow Merja Voutilainen study ALS with funding from the E-Rare ERA-NET.
Professor Mika Rämet, Chair of the Research Council for Health, appreciates the advantages of funding research into rare diseases: “Research into the mechanisms of rare diseases can often also lead to more insights about more common diseases. If, for example, a specific gene mutation causes a severe rare disease, a minor genetic anomaly can predispose to a more common disease.”
CDNF makes mice live longer
Saarma’s research team discovered the CDNF neurotrophic factor in 2002. In 2007, the team successfully proved the ability of CDNF to effectively protect and repair dopamine neurons in the brain and improve motor function in animal models of Parkinson’s disease.
“Now, we’re trying to figure out whether CDNF also works in mice models of ALS,” says Saarma’s colleague, Academy Research Fellow Merja Voutilainen.
Voutilainen and Saarma have studied ALS since 2013. Recently, they proved that CDNF can help treat ALS mice that carry the SOD1 gene mutation. According to Voutilainen, CDNF extended the lifespan of ALS mice by 17–25 per cent after just one injection.
“Basically, we injected CDNF into the mice brains and monitored the post-injection motor function and survival of the mice.”
Clinical trials in the pipeline
In the future, the CDNF neurotrophic factor may also be used to treat people with ALS.
“Herantis Pharma, a Finnish pharmaceutical start-up, has received an orphan drug designation for CDNF in both Europe and the US, a status reserved for drugs intended to treat rare diseases. This will speed up the process of getting CDNF into the clinical trial phase,” says Voutilainen.
The current plan is to start clinical trials in 3−5 years. Before that, however, the researchers must optimise the doses and investigate on mice whether long-term dosing works better than single-dosing. In addition, the effects of CDNF must be proven on human motor neurons and on another animal species, namely rats.
Although ALS is a rare disease, as Voutilainen points out, it causes a considerable economic burden on society. There are about 500 people living with ALS in Finland. A little under 200 Finns are diagnosed with ALS each year – approximately four new cases each week. The overall costs of treating a patient with ALS amount to hundreds of thousands of euros per year.
International collaboration is key to effective research into rare diseases
Both Saarma and Voutilainen work at the University of Helsinki Institute of Biotechnology, which is now an operative unit of HiLIFE, the Helsinki Institute of Life Science. Professor Pentti Tienari’s team is based at the University’s Faculty of Medicine.
“Pentti Tienari infuses knowledge of ALS genetics and clinical research into our project. He provides us with rare patient samples that we can use to make human motor neurons in vitro with the help of stem cell technology,” Saarma explains.
The other collaborators of the research project are Professor Michael Sendtner’s team from the University of Würzburg, Germany, and Professor Smita Saxena’s team from the University of Bern, Switzerland.
Mika Rämet considers international collaboration to be particularly important in rare diseases research. Without collaboration, collecting a sufficient amount of patient data could be an almost impossible task.
“Combining the strengths of multiple teams means that you can also raise the standard of your research and set more ambitious targets.”
The Academy of Finland will also participate in the tenth E-Rare joint call for multilateral research projects on rare diseases. The closing date for the first stage of the call is 6 February 2018. Read more about the call on the Academy’s website.
Original text in Finnish and profile photo by Tea Kalska
Header photo from Pond5