Dr. Mª Josep Martí: "The main aim is to slow down, stop or even reverse the processes of the disease”
Interview with Dr. Mª Josep Martí, neurologist and head of the IDIBAPS Parkinson’s Disease and other Neurodegenerative Movement Disorders research group. On the occasion of World Parkinson’s Day, we speak to her about what we know about this disease and where research is heading.
She is also the Coordinator of the Center of Reference CSUR for Rare diseases with Movement Disorders and Director of Hospital Clinic Health Care Provider of European Reference Network for Rare Neurological Diseases (ERN-RND)
It may develop silently from the age of 30, but the symptoms appear when people are in their 50s and 60s, and the frequency of the diagnosis increases with age. However, there are patients with early-onset Parkinson’s disease who develop symptoms in their 40s, 30s or even 20s. Most people who get early-onset Parkinson’s disease have inherited it, but it can also be hereditary in older patients. Nevertheless, hereditary Parkinson’s disease due to a mutation in a known gene only represents 10% of all cases. The rest are known as idiopathic forms, which means no specific genetic factors are involved and the cause is unknown.
When the motor symptoms appear - tremor, rigidity, and slowness of movement - 60% of the neurons in the substantia nigra in the brain are already affected. The substantia nigra is an area where dopamine is produced, which is known as the “feel-good hormone”. It is a neurotransmitter that controls mental, emotional and motor responses. In Parkinson’s disease, dopamine is lost because the neurons that produce it degenerate and that is why the motor symptoms appear.
In the next few years, I think that research into Parkinson’s disease will focus more on personalized medicine.
In May, the Hospital Clínic will launch the Healthy Brain Aging (HEBA) project funded by the Michael J. Fox Foundation, which is due to last for 5 years. It will be open to the general population who will answer an online questionnaire and an algorithm will be applied to the answers to determine which people are at high risk of developing Parkinson's disease. A group will be selected to undergo an olfactory test and some will go to the Hospital to be monitored and for their evolution to be observed. The aim is to diagnose the disease as early as possible, in the preclinical or prodromal phases. If we could detect those affected in these phases, we would be closer to the main aim of slowing down, stopping or even reversing the processes of the disease. In addition to Catalonia, the study is being carried out in two more locations, Innsbruck (Austria) and Kassel (Germany).
Prodromal patients are those who have a high risk of developing the disease, for example patients with a genetic mutation but who have not yet manifested the disease, or else they have symptoms that usually appear in the stage before the motor problems, tremor and slowness. These are constipation, lack of sense of smell (hyposmia or anosmia), and REM sleep behaviour disorder (nightmares and sudden body movements during sleep). Having suffered from depression or having a relative with Parkinson's disease also increases the risk. Is it important to select them as early as possible, because the disease starts well before the symptoms appear. This is the case in most neurodegenerative diseases. We have learnt that the disease starts many years before the symptoms appear.
For many patients, coming to the clinic is important, they know that they are cared for here and we work to help them.
It is a foundation made up of a large number of scientists and neurologists who are dedicated to the study of Parkinson's disease. It is one of the most important driving forces behind research into this disease and it allocates most money to its research. It was founded by the actor Michael J. Fox, famous for the film “Back to the Future”, and who was diagnosed with early-onset Parkinson's disease at the age of 29.
This foundation has a research project called the Parkinson’s Progression Markers Initiative (PPMI), which was launched 12 years ago and aims to study the progression and risk factors of the disease, in order to find a cure. Now this study is entering a second phase during which recently diagnosed and prodromal patients will be analysed. We have been involved in this since the start and are working actively in this second phase.
In recent years, we have been trying to act therapeutically on the possible cause of the disease. There is a protein called alpha-synuclein, which is thought to be passed from one neuron to another. People who have double or triple the normal alpha-synuclein levels have Parkinson’s disease, and this seems to be a clear cause. Stopping its progression could mean an improvement for many patients. It is know that this protein is misfolded and makes aggregates that enter the neuron and degenerate it. Some scientists think that these aggregates could be protective or at least not harmful. Following the first hypothesis, we have tried to work against this protein. However, to date this has not yielded the expected results. The more research we carry out and the more we learn, the more we realize that we still have a long way to go.
In the HEBA study, patients are selected as early as possible because we know that the disease starts long before the symptoms appear.
Because it is hard to access. When we study the brain of a person who died from this disease and was diagnosed maybe 30 years ago, the brain is no longer the same as it was when the symptoms first appeared. Many things have happened to this brain. For example, in the case of Alzheimer's disease, the PET (positron emission tomography) test makes it possible to see the evolution in the Tau protein or amyloid-beta peptides. On the other hand, in Parkinson’s disease we do not have any PET markers to detect the alpha-synuclein, and that is an additional complicating factor.
The more research we carry out and the more we learn, the more we realize that we still have a long way to go.
It is becoming increasingly clear that the research has to focus more on finding the molecular causes of this disease. Molecular causes that may be diverse. For example, the LRRK2 gene is currently being studied. The mutation of this gene may be responsible for a hereditary type of Parkinson's disease, but it could also contribute to the pathogenesis of the disease in a more general way. Another hypothesis is that “Parkinson’s disease” includes many different diseases, with specific molecular causes, as occurs with cancer. In the next few years, I think that research into Parkinson’s disease will focus more on personalised medicine.
We doctors want to cure our patients, and not being able to do so is frustrating, but at the same time it is stimulating because it is challenge to want to respond to their needs. I tell patients, especially now with the pandemic, “If you want, you don't have to come in, I can phone you”, but they tell me that they are looking forward to coming. Although some already know that we can’t help them much in terms of therapeutic options, for them coming to the clinic is important. They trust us and know we work to help them.