Current Research Protocols

Prevail Therapeutics PR001 Gene Therapy Trials 

(October, 2020)

Prevail Therapeutics is developing an investigational gene therapy called PR001 that has the potential to slow or stop the underlying disease process in patients with Parkinson’s disease with GBA1 mutations (PD-GBA) and neuronopathic Gaucher disease (nGD).

PD-GBA and Gaucher disease share the same underlying mutation of a gene, called GBA1. PD-GBA patients have mutations in at least one of their two copies of the GBA1 gene, while Gaucher disease patients have mutations in both GBA1 copies. The GBA1 gene contains the instructions for making the protein beta-glucocerebrosidase, or GCase.  GCase works in a compartment inside of cells called the lysosome, where it is responsible for the disposal and recycling of glycolipids (a type of fat). When there is an insufficient amount of active GCase, the lysosome does not function normally, which can lead to the symptoms seen in PD-GBA and nGD.

In order to deliver the healthy GBA1 gene to cells of the brain, PR001 uses a viral vector (or shuttle) called AAV9. AAV9 is a well-studied vector used by a number of companies developing gene therapy products, particularly those that target disorders of the nervous system.  The therapy is designed to enable brain cells to produce enough active GCase for lysosomes to do their jobs and potentially slow or stop the disease from progressing.

In clinical trials, PR001 is administered by a one-time injection into the cerebrospinal fluid space in an area above the spinal cord called the cisterna magna. This type of injection is a direct, non-surgical technique that has been used safely for other purposes for many years.

Parkinson’s Disease with GBA1 Mutations (PD-GBA)

Parkinson’s disease with GBA mutation (or PD-GBA) starts earlier compared to Parkinson’s disease in patients without this genetic mutation, with more severe symptoms and increased likelihood of dementia. It is estimated that as many as seven to ten percent of patients with PD worldwide, including some 90,000 patients in the United States, have at least one GBA1 mutation1.

Physicians and researchers can use patients’ genetic information — such as whether or not a patient carries a GBA1 mutation — to assist in diagnosis. This may also help to identify clinical trials of new potential therapies in development for which a patient might be eligible.

Prevail is recruiting patients for PROPEL, a Phase 1/2 clinical trial designed to evaluate the safety and effects of PR001 in patients with moderate to severe Parkinson’s disease who have at least one GBA1 mutation. Twelve study participants are sought for this Phase 1/2 trial, which is being conducted at several clinical sites. Don’t know if you have a mutation? Prevail offers programs for genetic testing at PROPEL clinical sites.

Learn more about the PROPEL clinical trial or contact the Prevail PROPEL recruitment team with questions or to express interest in study participation.

Type 2 (neuronopathic) Gaucher disease

Gaucher disease has three types, which vary by severity of symptoms, age of onset and the presence of symptoms that affect the brain. Type 2 and Type 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by symptoms that affect the brain.

Type 2 Gaucher disease, the most severe form, affects infants. It causes rapid, progressive and irreversible brain damage usually beginning in the first six months of life; children typically die by age two. Patients with Type 2 Gaucher disease are also affected by the symptoms of Gaucher disease that occur throughout the body, such as spleen and liver enlargement and blood abnormalities.

Prevail is recruiting patients for PROVIDE, a Phase 1/2 clinical trial designed to evaluate the safety and effects of PR001 in infants 0-24 months of age with Type 2 Gaucher disease. Fifteen study participants are sought for this trial that will be conducted at several clinical sites.

Learn more about the PROVIDE clinical trial or contact the Prevail PROVIDE recruitment team

with questions or to express interest in study participation.

  1. Blauwendraat C, et al. Genetic modifiers of risk and age at onset in GBA associated Parkinson’s disease and Lewy body dementia. BRAIN 2020.

Study Examining In-Utero Treatment of Gaucher Disease Types 2 and 3

The Univeristy of California San Francisco is conducting a study examining in utero treatment for nGD. Currently, children with Gaucher disease can be treated with enzyme replacement therapy (ERT) after birth, which slows the progress of the disease.

The clinicians conducting the study believe that giving ERT before birth could help patients with Gaucher even more. They have studied mice with a different lysosomal storage disease, Mucopolysaccharidosis type 7, and gave them ERT before birth. Mice treated with ERT before birth had better outcomes than mice treated with ERT after birth.

They are initiating a clinical trial to give ERT to fetuses with several lysosomal storage diseases, including Gaucher Types 2 and 3. The possible benefits of giving ERT before birth are avoiding the development of antibodies to the enzyme, crossing the blood brain barrier, and preventing the disease from starting to cause damage to the brain and other organs.

Engaging the patient community is crucial in developing novel therapies. As such, they are surveying Gaucher parents’ and patients’ attitudes towards fetal therapy.

The survey includes an introduction to the project as well as consent. If you have questions please contact Dr. Marisa Schwab.


Survey Study on the Association of GBA Mutations and Parkinson’s Disease

Researchers at the Icahn School of Medicine at Mount Sinai are seeking volunteers at least 18 years of age who are carriers of Gaucher disease, i.e. have 1 change in the GBA gene, for a survey study aiming to learn more about the attitudes and knowledge of Gaucher disease carriers on the  risk association of Parkinson disease. The study requires participants to answer an anonymous survey, taking less than 5 minutes to complete. For more information, contact Nora Nesheiwat at 212-241-9414.


Survey: Knowledge and Attitudes of Parkinson Disease Risk in the Gaucher Population

The Icahn School of Medicine at Mount Sinai has established a new research study geared to learning more about the perspectives of individuals with Gaucher disease. The goal of the study is to collect information on knowledge of and attitudes about the association between Gaucher disease and Parkinson disease.

Eligible participants for the online survey study are over the age of 18 and have a confirmed diagnosis of Gaucher disease. The survey is anonymous and will take approximately 5-10 minutes to complete.

This survey study was created as part of a master’s thesis project for genetic counseling student, Leah Zaretsky, under the mentorship of Dr. Manisha Balwani, Dr. Roy Alcalay, and Natasha Zeid MS, CGC.


Artifical Intelligence’s Effect on those living with Lysosomal Storage Disorders

Georgia Loucopoulos, Candidate for MMSc in Genetic Counseling at Emory University, is conducting a study that seeks to determine if ThinkGenetic.com, a website that utilizes artifical intelligence, helps those living with a lysosomal storage disorder. 200 participants are sought.

Eligible participants are individuals who have been diagnosed with a lysosomal storage disorder as well as any family members. It is a 3 part study consisting of a pre-survey, time for research on ThinkGenetic.com, and a post-survey. Participants who complete all three parts receive a $25 gift card for their time. Interested? Begin the study. Questions? Email Georgia directly.


Parkinson’s Progression Markers Initiative

Be part of the Genetics Research Revolution in Parkinson’s Disease

Individuals with Gaucher disease and those with Parkinson’s disease (PD) can share a common link: mutations in the GBA gene. Identifying and evaluating people who carry a GBA mutation, whether they have Gaucher disease or PD or are related to someone living with one of these diseases, is vital to helping scientists learn more and develop improved treatments.

The Parkinson’s Progression Markers Initiative (PPMI) is a landmark clinical study sponsored by The Michael J. Fox Foundation to better understand the progression of and risk factors for PD.

PPMI is currently studying the connection between PD and mutations in the GBA gene.

Individuals of Eastern European (Ashkenazi) Jewish descent are more likely than the general population to carry a mutation in the GBA gene. PPMI provides genetic counseling and testing for GBA mutations at no cost to individuals of Ashkenazi Jewish descent who:

  • Have Gaucher disease and are age 45 or older
  • Do not have Gaucher disease but are age 45 or older and have a first-degree relative with Gaucher disease
  • Have PD and are age 18 or older
  • Do not have PD but are age 45 or older and have a first-degree relative with PD

Visit WWW.MICHAELJFOX.ORG/PPMI/GENETICS to learn more about counseling and testing for this research study.


Rare Disease Self-Identification Tool

The Global Genes Medical and Scientific Advisory Board members in partnership with Engage Health, Inc. & LapidusData are developing an amazing tool that could significantly impact the rare disease community. It is called the “Rare Disease Self– Identification Tool. The tool will help patients and patient advocates understand that they may be affected by one of the 7,000 identified rare diseases.  You can help in the development of the tool by taking approximately 10 minutes to answer survey questions, HERE


Clinical Study on Parkinson Disease and Deep Brain Stimulation Seeks Participants

Participants sought for clinical study about the level of cognitive decline experienced by patients who have Parkinson disease and are treated with Deep Brain Stimulation (DBS). Parkinson disease affects at least 1 million people in the U.S. Each year, 9,000 Parkinson disease patients undergo deep brain stimulation placement; which improves their motor skills. Despite their motor improvement, up to 50% of patients have some level of cognitive (thought process) impairment after DBS. Carriers of mutations in the glucocerebrosidase (GBA) gene are at particularly high risk for cognitive impairment. This study seeks to determine the differences in cognitive decline between patients with Parkinson disease who are carriers of the GBA gene mutation as compared to Parkinson patients who are carriers of the GBA gene mutation without previous therapy with deep brain stimulation as well as non-mutation carriers with and without deep brain stimulation. Understanding if there is an association between the GBA gene and DBS will enable clinicians to identify individuals at risk for worsened cognitive dysfunction and prevent additional harm. Learn more at clinicaltrials.gov (NCT03234478).


Palo Alto University Research on the Psychosocial and Neurocognitive Impacts of Gaucher Disease Type 1 on Pediatric and Young Adult Patients

Andrea Alioto, M.S. and Wendy Packman, J.D., Ph.D of Palo Alto University are conducting a study on the psychological and cognitive impacts of Gaucher Disease type 1 on pediatric and young adult patients. The study is seeking more participants between the ages of 5 – 30 and their parents. Participation involves completion of questionnaires, both for parents as well as child/young adult, which are mailed to participants with a prepaid return envelope. Completion of questionnaires take 35 – 90 minutes. Learn more at http://gaucherstudy.com/.


Emory University Newborn Screening Study

Emory University is conducting a study pertaining to the perspectives about newborn screening for Gaucher disease. Eligible participants are 18 years or older who have a clinical diagnosis of Gaucher disease and are fluent in English. Participants will be scheduled for a 30-40 minute recorded telephone interview and will be compensated with a $25 Amazon gift card. If interested, please contact Nadia Ali, Ph.D. at 404-778-8613 or email her at nadia.ali@emory.edu.

 


GD Type 1 Survey: Understanding the Importance of Varied Aspects of Treatments

Sanofi Genzyme in collaboration with Mapi is recruiting patients with Gaucher disease type 1 to participate in a survey to understand the importance of different aspects of hypothetical treatments for Gaucher disease type 1. The survey will take approximately 60 minutes to complete during which patients will be asked to make decisions about which hypothetical treatment options they prefer. Participants will receive an Amazon gift card for the value of $100 for completing the survey.

If you are interested in taking part, please click on the link to see if you are eligible to participate.


Research study to investigate LSD patients’ perception of their treatment is recruiting Gaucher participants.

Dr. Amel Karaa, Clinical Director of the Lysosomal Storage Disease Program at Massachusetts General Hospital, is conducting a survey of Gaucher, Fabry and Pompe patients. Participation is completing a brief survey that takes approximately 15 minutes to complete. It will ask your opinion about the use of Enzyme Replacement Therapy (ERT) and Substrate reduction therapy (SRT). All surveys are anonymous and all information is de-identified. To take the survey, click on the link and follow the instructions.


Research protocol studying inflammation in those with GD Type 1 is recruiting participants

Are you an adult 18 years of age or older, who has been diagnosed with Gaucher disease and currently on stable treatment for at least 6 months? If so, there is a clinical trial in which you might want to participate. The research focuses on understanding the role of oxidative stress and inflammation in Type 1 Gaucher disease and examines whether a nutritional supplement improves these two factors. This study is recruiting patients throughout the United States. For more information, please click here.


Research protocol for Type 3 Gaucher is recruiting participants

A research study for an orally administered substrate reduction therapy treatment in Gaucher disease type 3 as part of the 2-part LEAP clinical research study. You may be eligible to participate if you are 18 years of age or older, have Gaucher disease type 1 (part 1 only) or have Gaucher disease type 3 (must complete part 1 to participate in part 2), and have received treatment with enzyme replacement therapy for at least 3 years and received Cerezyme at a stable dose for the past 6 months.
For more information, visit www.clinicaltrials.gov, using study identifier NCT02843035.


Research investigation for Type 2 Gaucher is seeking participants

This study is to investigate the current natural history of type 2 Gaucher disease. Participants are parents of children affected with Type 2 Gaucher (both alive and deceased). Research is being conducted at NIH through interviewing families to better chronicle the clinical course and complications encountered currently. A five page questionnaire will be used during the interview process that will be conducted via the telephone, which takes approximately 1 hour to complete. This questionnaire will consist of questions regarding his disease and the disease progression. If interested, please contact Tamanna at tamanna.roshanlal@nih.gov


Research study about bone involvement associated with Gaucher disease seeking patient participation.

Are you an adult 18 – 65 years of age who has been diagnosed with Gaucher disease and are not currently receiving treatment (within the past 12 months)? If so, there is a new research protocol enrolling participants that may be for you. The research focuses on the possible improvement in bone involvement associated with Gaucher disease.

This study is recruiting patients at several sites throughout the world. For more information, please visit www.gauchertype1study.com

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