Gaucher's disease is a rare pathology affecting one out of every 50,000 live births in its least aggressive form, and one out of every 100,000 births in its more serious variant. Andrés Klein, a cell and molecular biologist and researcher at the Weizmann Institute (Israel), found it interesting that a single mutated gene could provoke several forms of the disease, some of which are fatal and others chronic. So he embarked on research to find a way of predicting how each patient would be affected, and thus achieve early diagnosis and more individualized treatment. This is one of the reasons he was selected as one of the MIT Technology Review Innovators under 35, in its Chilean edition in 2013.
Why is the study of rare diseases interesting?
Because they are devastating and so little can be done for the patients. There's so much to do and we know so little that there's a lot of room to grow. What's more, Gaucher's disease has a greater incidence in the Ashkenazi Jewish population [originally established in central and eastern Europe], to which I belong. It's a pathology that affects the functioning of the enzyme GBA, which is responsible for cells correctly digesting nutrients. It has as an incidence of one out in 50,000 births.
What effect does the failure of that enzyme have on the organism?
In some cases it affects the brain, and the patients die when they're two or three years old. Others manifest a later onset of neurological symptoms and live for thirty or forty years. A third type attacks the internal organs like the liver and the spleen, and these people can lead a normal life with medication.
What determines whether or not it affects the brain?
We don't know, and that's why I began to study it, because I find it fascinating that a single mutated gene can sometimes affect the brain and sometimes the internal organs. The problem is that to reach valid conclusions you need thousands of patients with different symptoms –or at least several hundred– so you can compare their genomes. However these people don't exist, or haven't been diagnosed.
How can you study a disease without patients?
The great part is that I was able to imitate in mice what happens in humans. Thanks to a GBA inhibitor, I saw the same thing happened in mice as in people: some of them developed a very aggressive disease of the brain and lived a couple of weeks, whereas others made it to seven months. I was then able to make genetic studies on them to predict the development of the disease, as well to design therapies which succeeded in making the mice live between three and four times longer.
Would those discoveries in mice be applicable to humans?
That's what we're looking at now. We've recruited a small group of patients with a range of symptoms and we're going to see if the tool that predicts in mice is valid for humans. We want to be able to predict what type of disease a patient is going to present. But predicting is not curing. This is the path towards personalized medicine. It's not enough today to know what disease a patient has. If we can determine early on that the patient is going to develop a type of pathology that affects the brain, we can treat it in a different way.
Is personalized medicine the future?
One hundred percent. What's more, the strategy I follow could be used for other diseases so we can find out why certain patients are more resistant to viruses. From here we can design new therapies to block certain pathways or genes.
The ice bucket challenge has succeeded in raising funds and creating awareness of ALS, which is also a rare disease. How do you rate this type of initiative?
Creative ways of raising money for research are always welcome. I think it's been really useful and it's a very interesting strategy. Sites like Facebook mean these things quickly go viral. I'm convinced these creative ideas help raise awareness. We need to come up with something different but equally creative for lysosomal diseases, which are less widely known than ALS.
Creative ways of raising money for research are always welcome"
Could similar campaigns be done other rare diseases?
The ice bucket challenge was a great idea, and we'd have to get a marketing specialist to think up other initiatives. There are already some out there, but they're very typical, consisting of interviews with parents and patients. This has much less impact now than 15 years ago. Social media have certain advantages, and we have to make the most of the connectivity in the world to raise awareness.
In the film "Lorenzo's oil" it's the parents of the protagonist –who suffers from a rare disease– who fight to obtain a treatment. Is this usual?
It's quite common. Resources are scarce and it's difficult to obtain funds, but parents motivate us to research, and they themselves raise money through the foundations they set up. They're desperate to see their children get better, or at least suffer as little as possible. There's no doubt they're the ones that make the greatest efforts and give meaning to what we do.
Will a cure for this type of disease be found some day?
Definitely, and it'll be thanks to gene therapy. These are genetic diseases that cause deficiencies in certain proteins. It's essential to know how far the disease is reversible, because if there's already been a massive death of neurons there's no point in replacing the gene, as the neurons that have been lost cannot be regenerated.
Is the future of medicine a combination of gene therapy and personalized medicine?
For this type of disease, yes. I believe that early diagnosis accompanied by gene therapy will succeed in curing many of them. But we need to know how the disease is going to develop in patients. We may be able to stop the progression of the disease, but the neurons that have been lost are gone forever.
Wouldn't it be possible to regenerate the neurons in these patients?
There is some neuronal regeneration in specific parts of the brain, but here we're talking about massive neuron death. The best way to fight it is to find good systems for early diagnosis and then apply gene therapy, and meanwhile to look for therapies that although they can't cure, can relieve the symptoms. This is essential, because when you have a headache you can take an aspirin without needing to know why it hurts.