This interview was originally posted on the Hitfar website in February 2017. Thank you to Hitfar for giving ALS Canada permission to re-post this content.
Could you start by explaining the disease and its effects?
ALS is a disease where the living wires, called motor neurons, that connect your brain to your muscles die. This means when the brain wants to signal your muscles to move, it cannot. Muscles are made up of thousands of tiny muscle cells and each cell is connected to the brain by one chain of an upper and lower motor neuron. Initially a muscle may feel weak, as these cells become disconnected from the brain and eventually the muscle will become paralyzed. ALS spreads from an initial site throughout the body and starts typically with arm or leg weakness (limb onset), or altered speech (bulbar onset). Eventually, the muscles that regulate swallowing will be affected and the disease is terminal as the muscles controlling breathing become paralyzed. Other muscle symptoms like cramps and twitching are often experienced, but are not indicators of ALS. On average, an individual with ALS will die from the disease 2 to 5 years after diagnosis, but this can vary greatly and the course of the disease is quite individual in nature. There are no effective treatments and only one approved drug, called Riluzole that has minor effect in some individuals.
As of today, do we know if all people have a genetic predisposition to ALS or this disease is hereditary only?
Five-10 per cent of ALS cases are hereditary in nature and can be passed on from parent to child through a gene mutation. The remainder of the 90+% of cases are known as sporadic ALS because we don’t know the exact cause(s). Many researchers believe that some individuals may be genetically predisposed to ALS based on the symphony of multiple genetic factors rather than a single gene mutation. It is also believed that environmental factors and exposures may play a role in triggering the disease. Only through looking at the entire set of DNA (called the genome) for people with ALS versus those without (controls) can we start to find these commonalities in genetic signature that might make someone susceptible. This will have to be done in tandem with other information about each person to fully understand how genetics and environment might work together to cause ALS.
Do we have any progress in finding the cause of ALS?
In the past five years, we have gained more knowledge about the cause(s) of ALS than in all of time before. There are two primary reasons for this. First, is the advancement in genetic discovery. Each new genetic cause of ALS that is identified, provides a tool to make models of the disease in the laboratory and provides biological pathways to examine for a better understanding of how it is caused. Prior to 2011/2012, we had only a few of these tools to work with, but since, we have identified many. Simultaneously, we have gained a better grasp on the functions of those genes we had been studying before 2011/2012. As we start to unravel the importance of all these new genes, connections will be made that lead to new treatment options. The second reason is the advancement of technology to study ALS. The past five years have seen leaps in our abilities to both look at the disease in the laboratory and deliver potential treatments in the clinic. In addition, the potential to execute large initiatives that are centred around studying human ALS (precision medicine) has become a reality only recently as the cost was prohibitive before. These precision medicine studies will use a multitude of modern techniques to example samples from people living with ALS for specific biological signatures that might explain how ALS is caused. We are certainly poised, provided there is sufficient funding, to have far more information about ALS in the next few years than all of time up to now.
ALS is a global problem, but is there a global collaboration between countries? Can you elaborate on project MinE?
There are many global collaborations between countries aimed at studying ALS. One of these is Project MinE, which is a consortium of 17 countries that are contributing full DNA scans (called whole genome sequencing) of people living with ALS to a central, open access database. Each country is raising funds and recruiting samples to contribute. Whole genome sequencing was too expensive for such a study until recently and even at the current cost, the entire project, aimed at sequencing 15,000 people with ALS and 7,500 controls for comparison, will still cost between $30 and $40 million. Such a high cost and number of samples is not something that would be feasible by any one country. In the end, the hope is to have enough information to see genetic signatures that can confer susceptibility to ALS and ultimately, identify new targets for potential treatment.
In our lifetime, what do you think we can achieve in terms of ALS research?
I believe that in the foreseeable future ALS can be a treatable, manageable disease where it is diagnosed as a chronic illness that is no longer terminal. With treatments to slow down the progression combined with ways to diagnose earlier, I think that there is a good chance we can create a world where ALS is something people live with over a long period of time. It is also conceivable that a combination of diagnosis prior to symptom onset, combined with disease slowing treatments could provide a cure in the sense that people may never experience weakness or paralysis despite still having the disease (akin to management of HIV infection). I would also never rule out the possibility of an outright cure in the future as technology of the past few decades has proven that we will be able to do things that we cannot yet conceive.
What is the biggest challenge that ALS research faces?
The biggest challenge that ALS research faces is funding. Our research community has come very far with very little in comparison to annual funding levels of diseases with treatment options. The disease is very complex, but we are making tremendous headway. Unfortunately there are far more things to examine than financial support available.
Where are you getting the majority of funding currently?
The majority of ALS Canada’s research funding has come from the WALK for ALS events across Canada, for which 40 per cent of money raised goes to a national research program. This provides between $1.5 and $2 million per year. In 2014, the world came together to support ALS through the Ice Bucket Challenge and $10 million raised for research was matched by the federal government through Brain Canada. This $20 million program has provided a great stimulus to ALS research, but it is still very little in comparison to the annual research budget of most treatable disease non-profit programs. The last $1.8 million will be allocated through a grant program in 2017, following which all funding in Canada will return to the amounts raised by the WALKs.
What do you think can be done to accelerate the path to a cure?
I believe researchers are on the right path to at least making ALS treatable. The best thing that can be done is to find ways to fund these studies as there are easily far more things that can be done than there are resources to allow. I believe we will get there, but the speed will ultimately depend on the ability to do this work.