Moving from Symptomatic Management to Early Intervention in Parkinson’s Disease patients

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Currently, there is no way to slow the progression of Parkinson’s disease (PD). The focus of PD treatment is currently only on symptomatic management. To be able to optimally recognize and treat the different PD subtypes and their progression, the DUPARC cohort was established six years ago. However, in order to modify disease progression, intervention as early as possible is needed, even before the typical motor symptoms of PD start to occur.

Parkinson's disease (PD) is not a uniform disease, but a syndrome, consisting of a diversity of symptoms This makes early recognition complex; many and very different symptoms have to be recognized. Generally, PD is considered to be a pure motor disorder. However, the disease actually exists mainly of so-called non-motor problems, including cognitive problems, depression, apathy and problems with sleep, and the maintenance of a sufficient blood pressure.

Dutch PARkinson and Cognition cohort (DUPARC)

Prof. Dr. Teus van Laar is the initiator of the DUPARC cohort, a de novo PD cohort with 150 participants (not being treated at baseline)  that collects clinical data via multiple questionnaires, genetic- and lab data and extensive imaging with PET scans and MRIs, every 3 years. The primary goal of DUPARC is to develop and expand personalised treatments based on PD subtypes. On the test days, participants are fully serviced, including  taxi transportation to the UMCG. According to Prof. Dr. Van Laar, it is important to cherish this vulnerable group, because they participate without any personal benefit and without immediate results for themselves. At the annual patient day, participants receive feedback on DUPARC's developments, results, and future plans, and they can meet the involved researchers.

International network

Although DUPARC is a Groningen-based cohort, it collaborates internationally with other parties in the field of Parkinson's, such as another Finnish de-novo cohort, the GP2 cohort, and other Parkinson expertise centers in Denmark, the United States, and Germany. In addition to international connections, there are close links with all hospitals in the northern Netherlands, joined in the Parkinson Platform Northern Netherlands (PPNN). DUPARC also works extensively with other departments within the UMCG, such as Psychiatry, Neuropsychology, Cell Biology, Microbiology, Genetics, and ERIBA.

Gene Mutations in 1 out of every 6 Parkinson's Disease Patients

The DUPARC study  has already resulted in clinically important results. For example, it has been shown that  already 20% of the de novo PD population has significant cognitive problems, which is accompanied by changes in the neurotransmitter levels of acetylcholine. De novo PD patients seem to have a specific profile of degeneration of their retina, completely different from what is seen in patients with glaucoma.

Also the fecal samples of de novo PD patients are significantly different from healthy controles, which is very likely related to the start of the disease in about 50% of the patients. Genetic mutations also play an important role in about 20% of all PD cases, including a frequently occurring mutation in the GBA gene, which  occurs in about 15% of all patients. Patients with this GBA mutation are now treated with a repurposed drug, ambroxol, originally used as a solvent of mucus, however in much lower dosages.

PRODROMAL

Prodromal Parkinson's is an early phase of Parkinson's disease in which symptoms and signs are present, but the characteristic motor symptoms are not yet fully developed. During the prodromal phase, various non-motor symptoms can occur, including:

  • Loss of sense of smell (anosmia)
  • Sleep disorders, such as REM sleep behaviour disorder
  • Constipation
  • Depression or anxiety
  • Fatigue
  • Reduced cognitive function

Together with Lifelines, we are in the process of setting up a cohort of prodromal PD patients, because they represent the very early phases of the disease, which provide the highest chance of modifying the disease progression.