Alzheimer Disease Q&A with Nick Cochran, PhD
Nicholas Cochran, PhD, is a postdoctoral fellow in the Myers lab at HudsonAlpha where he investigates the genetic risk factors or causes of neurological diseases.
All neurological diseases are interconnected. At Hud-sonAlpha Institute for Biotechnology, scientists are using cutting-edge technology to better understand neurological diseases, such as Alzheimer disease and frontotemporal dementia. While some advances have been made in treating the symptoms of these conditions, it is critical that we learn more about the genetic factors involved in these devastating and debilitating diseases.
Finding answers about one neurological disease may lead to answers about many of them. To help speed discovery, HudsonAlpha has es- tablished the Memory and Mobility Fund (M&M Fund) to support new projects and continue existing work in a variety of neurological diseases. One project in particular aims to sequence the genomes of more than 1,500 patients with Alzheimer disease and frontotemporal dementia.
How common is Alzheimer disease in the U.S.?
More than five million Americans have Alzheimer disease. Every 66 sec- onds, someone new is diagnosed with the disease.
If a family member has Alzheimer disease, what is the likelihood that I will also receive a diagnosis?
Estimates for this vary widely, and it is likely because the answer de- pends largely on the age of onset for the family member. For example, if your sibling or parent had Alzheimer disease and was diagnosed be- tween ages 65 and 85, risk of a diagnosis with earlier onset Alzheimer disease is lower for you. However, if family members happen to have onset before age 65 in multiple generations, it’s a good idea to contact a neurologist and/or geneticist, because this is rare and could have a very strong genetic component.
What types of treatment options are available?
There are currently two treatments for Alzheimer disease. Neither addresses the underlying cause of the disease. Both can “plateau” progression for about 6 months. Together, they can delay nursing home place- ment by about two years, so they do have a measurable benefit, but there is a lot of room for improvement.
What advancements have been made so far in Alzheimer disease at HudsonAlpha?
At HudsonAlpha, we have been positioning ourselves to analyze whole genomes for Alzheimer disease and other types of dementia. The word “analyze” is important here because there are a few other places that have been sequencing whole genomes for Alzheimer disease and other types of dementia, but the expertise at HudsonAlpha is really top-notch for analyzing the whole genome, and not just the part coding for proteins.
The other thing we’ve gotten off the ground recently is cultures of human brain cells – neurons, as well as supporting cells. We’re not doing anything scary to get the human brain cells – we are simply us- ing cells that were re-programmed from an adult’s skin cells. Having this type of culture available allows us to mimic the types of genomic changes we find in patients, which can help provide evidence for or against a given genomic change being associated with disease.
How is studying the genomes of Alzheimer patients going to advance our knowledge of the disease?
With science we can never guarantee anything going in, but what we can do is position ourselves for suc- cess as well as possible given what’s worked well in the past. So, we’ve done that with Alzheimer disease and related dementias by selecting a group of samples from patients that are highly likely to have one underlying cause of their disease. Specifically, these are earlier onset and/or atypical cases of Alzheimer disease and frontotemporal dementia. Earlier onset cases are more likely to be strongly genetic. We could learn a few different things from these data. One critical thing is that we could find new genes that have variants that cause disease. This is critical because it’s only by knowing what genes have variants that cause disease that we can take any kind of rational approach for therapeutic development. Another key set of observations we could gain from these are identifying biomarkers of disease. We will be mak- ing measurements of immune response, which has come into the limelight in the research field recently as being very important.
How far away are we from a cure?
Often what people really want to know is how close we are to effective therapies, which can be almost as good as a cure. The first key idea is that prevention is going to be the name of the game. There has been a lot of work lately showing that the most effective therapies in development are performing the best in people who have very mild symptoms. This is probably due to the fact that based on work done recently, we now know that the underlying disease process starts decades before symptoms. So, if we can target that process before symptoms, that would be even better and screening tools are in active development (and some are already approved) with the hope of doing just that. For Alzheimer disease, I would speculate that if we could get to two or three effective therapies, targeting the underlying disease process, we could make an impact on prevention that is very tangible. Some of these are close to completion, and more and more will read out over the next 5 to 10 years.
What other neurological disease research is happening at HudsonAlpha?
We are doing and have done quite a lot of work in different neurologic diseases, from childhood intel- lectual disability and developmental delay, to major depression and schizophrenia, to other adult-onset neurologic diseases like Huntington’s disease, Parkinson disease and ALS. I think we gain a lot of synergy by doing this, because while these are distinct diseases, we can often learn things about one disease from another, both from commonalities and differences between them.