Genetic Registry for Parkinson's Disease

Recruiting at 49 trial locations

Overseen By Irene Andonia Malaty, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Parkinson's Foundation

Disqualifiers: Atypical parkinsonian disorders, Hematologic malignancies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

25000 Participants Needed

Trial Summary

What is the purpose of this trial?

Development of a central repository for PD-related genomic data for future research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment in the Parkinson's Foundation PD GENEration Genetic Registry?

The research indicates that certain genetic mutations, like those in the LRRK2 and GBA genes, are significant in Parkinson's disease and could be targeted by new therapies. This suggests that understanding genetic factors can help develop effective treatments for Parkinson's disease. ^{1 2 3 4 5}

Is the genetic registry for Parkinson's disease safe for humans?

The research articles do not provide specific safety data for the genetic registry or related treatments, but they focus on understanding genetic factors in Parkinson's disease, which is generally considered safe as it involves genetic analysis rather than direct medical intervention. ^{1 2 6 7 8}

How does this genetic registry treatment for Parkinson's disease differ from other treatments?

This genetic registry for Parkinson's disease is unique because it focuses on collecting and analyzing genetic data to understand the role of specific gene mutations in the disease, which can help in developing targeted therapies. Unlike traditional treatments that address symptoms, this approach aims to uncover genetic causes and inform future personalized treatment strategies. ^{1 2 8 9 10}

Research Team

Roy N Alcalay, MS, MD

Principal Investigator

Tel Aviv Sourasky Medical Center, Columbia University Irving Medical Center

James Beck, PhD

Principal Investigator

Parkinson's Foundation

Eligibility Criteria

This trial is for adults with a probable diagnosis of Parkinson's Disease who are willing to undergo genetic testing and can give informed consent. They should be able to complete surveys and may include family members if additional genetic confirmation is needed. It excludes those under 18, recent bone marrow transplant or blood transfusion recipients, and individuals with atypical parkinsonian disorders or active blood cancers.

Inclusion Criteria

Study Population 1: PWP (open for recruitment)

Study Population 2: People at risk of developing PD (not open for recruitment)

My family may join the study if genetic testing is needed.

Exclusion Criteria

I am younger than 18 years old.

I have been diagnosed with a rare form of Parkinson's disease.

I have received a blood transfusion in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genetic Testing and Counseling

Participants undergo genetic testing and receive counseling to learn about their genetic mutation status

6 months

Data Repository Development

Participants' genomic data and residual DNA are deposited into a central repository for future research

6 months

Follow-up

Participants are monitored for safety and effectiveness after genetic testing and counseling

4 weeks

Treatment Details

Interventions

• Parkinson's Foundation PD GENEration Genetic Registry

Trial Overview The study aims to create a central database by collecting genomic data from participants related to Parkinson's Disease. This registry will support future research on the genetics of Parkinson’s Disease by analyzing genes like GBA, LRRK2, SNCA, VPS35, PRKN, PINK-1, PARK7.

Who Is Running the Clinical Trial?

Parkinson's Foundation

Lead Sponsor

Trials

13

Recruited

1,030,000+

Parkinson's Study Group

Collaborator

Trials

1

Recruited

25,000+

Indiana University

Collaborator

Trials

1,063

Recruited

1,182,000+

Fulgent Genetics

Collaborator

Trials

1

Recruited

25,000+

The Parkinson Study Group

Collaborator

Trials

17

Recruited

32,500+

Findings from Research

The MDSGene initiative, launched in 2016, has compiled over 1150 genetic variants from approximately 5700 movement disorder patients, providing a valuable resource for understanding monogenic forms of Parkinson's disease (PD) and aiding in genetic counseling and research.

Despite its extensive database, MDSGene faces challenges such as the need for refined criteria for causative gene designation, significant clinical data gaps, and the limitation of only capturing published data, highlighting the need for further expansion to include unpublished cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDSGene: Closing Data Gaps in Genotype-Phenotype Correlations of Monogenic Parkinson's Disease. Klein, C., Hattori, N., Marras, C.[2023]

In a large UK study of 2262 participants, 1.4% were found to carry pathogenic mutations related to genetic Parkinson's disease, with notable mutations in LRRK2, PRKN, and PINK1, indicating a significant genetic component in this population.

Young-onset patients with PRKN and PINK1 mutations exhibited distinct clinical features, such as more postural symptoms and less cognitive impairment, suggesting that these genetic factors could influence the progression and presentation of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic analysis of Mendelian mutations in a large UK population-based Parkinson's disease study. Tan, MMX., Malek, N., Lawton, MA., et al.[2021]

A global network of 59 research sites has been established to study monogenic Parkinson's disease (PD), addressing the significant knowledge gap in underrepresented populations, as most existing data is from individuals of European White ancestry.

This initiative includes the development of an interactive online tool to facilitate collaboration and resource sharing among researchers, which is expected to enhance the development and testing of new therapies for both monogenic and idiopathic PD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson's Disease Project. Vollstedt, EJ., Madoev, H., Aasly, A., et al.[2023]

In a study of 262 Parkinson's disease patients, GBA mutations were found in 3.5% of cases, indicating a significant genetic contribution to the disease in the community.

GBA mutation carriers showed a significantly higher risk of progressing to severe motor disability and dementia, with hazard ratios of 4.2 and 5.7 respectively, suggesting that GBA status could serve as a prognostic marker for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort. Winder-Rhodes, SE., Evans, JR., Ban, M., et al.[2022]

Patients with genetic forms of Parkinson's disease (PD) have been followed for over 20 years, revealing distinct prognoses that differ from sporadic cases, highlighting the importance of genetic factors in disease progression.

Emerging therapies may be tailored to the specific genetic causes of PD, suggesting a future where treatment is personalized based on an individual's genetic background and the biological effects of their specific mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Genetic Parkinson's Disease. Aasly, JO.[2020]

Significant progress has been made in identifying genetic factors associated with Parkinson's disease (PD), including highly-penetrant mutations in genes like SNCA, LRRK2, and Parkin that cause rare forms of the disease.

Recent advances have highlighted specific mutations, such as VPS35 in autosomal dominant PD and DNAJC6 and SYNJ1 in recessive juvenile parkinsonism, but many genetic determinants remain unidentified, indicating that new sequencing technologies may help uncover more about PD's genetic landscape.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetics of Parkinson's disease--state of the art, 2013. Bonifati, V.[2022]

In a study of 504 nuclear families comprising 2828 individuals, researchers found that about 40% of the risk for developing Parkinson's disease (PD) is attributed to unidentified genetic factors, after accounting for known genes.

The heritability estimate of 0.41 indicates that while genetics play a significant role in PD susceptibility, environmental factors also contribute to the risk of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The heritability of risk and age at onset of Parkinson's disease after accounting for known genetic risk factors. Hamza, TH., Payami, H.[2022]

Genetic factors play a significant role in the development of Parkinson's disease (PD), with specific mutations in genes like SNCA, Parkin, and LRRK2 linked to rare, monogenic forms of the disease, while other variants increase risk in certain populations.

Despite the identification of these genetic risk factors, no effective treatments have emerged from this research, highlighting the need for further studies to understand the biological effects of these variants and their implications for PD therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. Hernandez, DG., Reed, X., Singleton, AB.[2022]

The discovery of alpha-synuclein mutations as the first genetic cause of Parkinson's disease (PD) has led to the identification of several other Mendelian mutations, including those in the parkin, DJ-1, PINK1, LRRK2, and ATP13A2 genes, highlighting the genetic complexity of PD.

Low-penetrance mutations, particularly the LRRK2 Gly2019Ser variant, along with polymorphic variants in alpha-synuclein and LRRK2, are becoming important genetic factors for sporadic PD, indicating that understanding these genetic influences is crucial for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetics of parkinsonism. Bonifati, V.[2021]

Research has identified over 13 genetic loci and 9 genes associated with Parkinson's disease (PD), with mutations in the alpha-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2) genes being significant contributors to both familial and sporadic forms of the disease.

Future research aims to uncover more genetic factors influencing PD, including susceptibility variants and gene-environment interactions, which could enhance our understanding of the disease and lead to better prevention and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parkinson's disease: from monogenic forms to genetic susceptibility factors. Lesage, S., Brice, A.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

MDSGene: Closing Data Gaps in Genotype-Phenotype Correlations of Monogenic Parkinson's Disease. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Genetic analysis of Mendelian mutations in a large UK population-based Parkinson's disease study. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson's Disease Project. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Genetic Parkinson's Disease. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Genetics of Parkinson's disease--state of the art, 2013. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The heritability of risk and age at onset of Parkinson's disease after accounting for known genetic risk factors. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Genetics of parkinsonism. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Parkinson's disease: from monogenic forms to genetic susceptibility factors. [2022]