Experts Call for Expanded Educational Initiatives on… : Neurology Today – LWW Journals

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Parkinson's disease specialists and patient advocacy groups have teamed up to promote greater education around the value of genetic testing for Parkinson's disease patients.

The field of genetic research for Parkinson's disease (PD) is evolving rapidly, as access to testing becomes more readily available and a growing number of novel therapies are in development and recruiting for clinical trials. In response, experts in neurology and genetics are calling for expanded education of medical professionals, patients, and the public to ensure accurate information, well-informed decision making, and ultimately better research.

One such initiative by neurologists, genetic counselors, and research staff from Indiana University, Northwestern University, and the Michael J. Fox Foundation (MJFF), has been a proposal to the AAN, outlining a widespread educational partnership targeting general neurologists and the patient community that would accompany efforts by the MJFF to offer greater access to no-cost genetic testing.

Therapeutic development for PD is entering a new and important realm of personalized medicine, said Tanya Simuni, MD, director of the Parkinson's Disease and Movement Disorders Center at Northwestern University, and a member of the nine-person team that developed the proposal. Although a single gene variant is not the cause of disease in the majority of individuals, studies of the small percent of mutation carriers have allowed better understanding of the biology of both genetic and sporadic forms of the disease, she said.

The MJFF and other organizations are working to increase awareness about PD genetics and availability of testingand neurologists have a key role to play in these efforts, Catherine Kopil, PhD, director of research partnerships at MJFF, and Tara Hasting, senior associate director of patient engagement at MJFF, wrote in an email to Neurology Today.

Professionals need up-to-date, structured informational and educational tools to share with patients, they said, specifically as a new MJFF initiative will be offering no-cost, remote targeted PD genetic testing, return of results, and telemedicine genetic counseling for individuals who are at increased risk of carrying the most common PD genetic mutations and who ultimately could qualify to participate in clinical trials. Genetic testing is a complex, expensive, and sensitive topic in any field of medicine, they added.

A consistent message is necessary for patients and families, specifically from neurologistswho will often be on the frontlines of the discussionfor addressing both positive and negative results, the genetic counselors and project managers from the Indiana University School of Medicine pointed out.

Clinical practice guidelines for genetic testing in PD have been limited thus far, Tatiana Foroud, PhD, chair of the department of medical and molecular genetics at Indiana University School of Medicine, said, but that is changing as interest and research in this field grows. As of today, the two genes that are the focus for current trials are GBA and LRRK2, both of which are associated with the more typical, later onset PD.

In the past, knowledge of an individual's mutation status did not significantly affect the clinical care for the majority of PD patients. However, there are ongoing clinical trials that are recruiting PD patients with a mutation in LRRK2 or GBA. Based on the opportunity to participate in ongoing clinical trials, individuals with a strong family history of PD and/or particular ethnic background may want to consider genetic testing for LRRK2 or GBA mutations, Dr. Foroud said.

Genetic discoveries have been revolutionizing PD for the past two decades, the proposal team wrote in an email to Neurology Today, but the new drugs in development are particularly exciting. Our ultimate success will require close collaboration between the scientists, the neurology professional community, patient advocacy organizations, and obviously patients.

In conversations with Neurology Today, neurologists who treat PD and neurogeneticists echoed the call for increased educational programs targeting both the neurologist and the patient and caregiver communities to accompany the ever-changing landscape of PD genetic research.

For decades, and certainly while I was training, we were told that Parkinson's wasn't really a genetic disorder. Now, as a field, we are increasingly aware of the importance of the genetic contribution to PD, said Claire Henchcliffe, MD, DPhil, vice chair of clinical research and chief of neurodegenerative disorders at Weill Cornell Medicine.

The percentage of patients with a monogenic mutation accounting for PD is still in the minority, she noted, but the more we know, the more complex the story becomes. I think what makes it so complicated to educate patientsand neurologists as wellis that we've already got different modes of inheritance that we have to talk about in terms of monogenic Parkinson's, such as autosomal recessive or autosomal dominant. On top of that we've got issues of penetrance and the complexity of multiple risk alleles. So this is not your genetics 101, this is really complicated. Dr. Henchcliffe said it would be helpful to have guidelines or structured main talking points for neurologists and other clinicians to use with their PD patients.

Joshua M. Shulman, MD, PhD, associate professor in the departments of neurology, molecular and human genetics, and neuroscience at the Baylor College of Medicine, agreed that the field is changing very quickly, and although it is still not routine practice to test or recommend PD patients for genetic testing, the conversation is shifting as the number of clinical trials grows.

Currently, experts told Neurology Today that most of the patients they recommend for genetic testing are those with suspected LRRK2 or GBA mutation who have a higher probability of qualifying for clinical trials, as well as those with atypical presentation or early age of onset.

There are disease-specific and context-dependent issues that arise with genetic testing for PD, which is still a relatively new field for many neurologists, Dr. Shulman said. What's interesting to consider, he added, is that many clinical trials are currently restricted to GBA and LRRK2 forms of PD, but might that change in the next few years?

There are many other genetic variants that have been linked to Parkinson's disease. So one might imagine that we could see other trials on the horizon where individuals with specific forms of the disease will be recruited to such trials. Further, there is increasing evidence that specific genetic variants can provide clinically valuable prognostic information about certain disease-related complications or rate of progression, for example.

Patients need to have a uniform set of data and terminology in this delicate area of science, Christopher G. Goetz, MD, FAAN, director of the Parkinson's disease and movement disorders program at Rush University Medical Center, said. In my experience, I find that misinterpretation, fear, and guilt are common among patients who access genetic information, and they must have professional guidance to place the information in a context that is useful.

He added, If the AAN gets involved with such programs, I urge an insistence on responsible pre- and post-testing professional support that addresses the individual's concerns in addition to the actual testing. Broad-based testing without this type of support will not advance the field and in fact could be a disservice in my view.

Other important areas for educational initiatives, Dr. Shulman suggested, for neurologists particularly are going to have to do with who should be tested, are which specific genes and variants should they be tested for, how to communicate that information back responsibly, and what the thresholds are for bringing in other genetic expertise, such as a clinical geneticist or genetic counselor.

There are many educational challenges to address on the patient side as well, Dr. Shulman said, such as the nuanced discussions with patients and family members about risk. Knowing that your Parkinson's disease is caused by the gene LRRK2 may have implications for significant risk associated with carrier states in family members. In the case of other genetic variants, such as GBA, the risk to family members is much lower. It can be harder to convey this more modest risk to family members and the public, he said, and this is one area where education could help.

Evidence is accumulating that patients and their families want this type of genetic information, Dr. Shulman said, which raises the question of whether we should be testing more comprehensively for possible genetic contributions to PDand if we're going to do that, what specific genetic variants should we be looking for and how do we communicate those results in an ethical and responsible manner?

A lot of the emphasis of genetic testing in the past has been solely for research or to better understand the pathways that play in PD pathogenesis, said Dr. Henchcliffe, adding that the results were not generally seen as being actionable. Now, I think the really exciting thing is that we can offer the testing in an era where we can start to do something about it. Although we don't have treatments that are yet FDA approved for specific genetic subtypes of Parkinson's, there are several clinical trials that are attempting to test such genetically targeted therapies. So I think that this is really an area for optimism in terms of advancing treatments for Parkinson's.

Still, she continued, this means the onus is on us as a medical community to provide our patients with PD with the information that they need in order to take the next step, especially as more organizations and consortia are beginning to offer testing and making it more widely available.

Depending on the specific type of test that's going to be employed, neurologists, patients, and families need to understand what they're getting into and what might be discoveredand also what might not be discovered, Dr. Shulman said. In other words, there is still an incomplete understanding of PD genetics.

So when we don't find that somebody has a genetic cause for their disease, that doesn't mean it's not genetically influenced, it just may mean that it's not found on one of the tests that we have available, Dr. Shulman said.

An important question to consider then, he added, is: How do we match genetic testing in clinical practice with a rapidly changing fieldwhere almost every month, new genetic findings are emerging and any test we do today may rapidly be out of date?

At this point, Dr. Goetz said, individuals at high-risk for monogenic specific forms of PD are prime candidates for testing, since they are most likely to benefit from gene-based therapy. On the other hand, The broad movement to gene-test even when specific treatments are not available is based on the premise that new gene-specific therapies will eventually be developed and patients want to be ready. The alternate approach, however, is to develop the putative therapies first and then solicit patients to come forward and be tested. In this case, the developer of the therapy would take the burden of testing and counseling whereas with the proposed be ready approach, foundations, governments, or agencies, including the AAN, take on the responsibility.

We need broad engagement with the neurologic community and patient communities to understand the best way to proceed. I think that's an important role that the AAN can play, Dr. Shulman said.

Dr. Simuni has served as a consultant for Acadia, Abbvie, Accorda, Adamas, Allergan, Amneal, Anavex, Aptinyx, Blue Rock Therapeutics, Denali, General Electric ( GE), Neuroderm, Neurocrine, Sanofi, Sinopia, Sunovion, TEVA, Takeda, Voyager, US World Meds, Parkinson's Foundation, and the Michael J. Fox Foundation for Parkinson's Research; has served as a speaker and received an honorarium from Acadia and Adamas; is on the scientific advisory board for Anavex, Neuroderm, Sanofi, and MJFF; has received research funding from the NINDS, Parkinson's Foundation, MJFF, Biogen, Roche, Neuroderm, Sanofi, Sun Pharma, Abbvie and IMPAX. Dr. Goetz has received honoraria from Oxford Biomedica; grants/research funding to Rush University Medical Center from NIH, Department of Defense, and Michael J. Fox Foundation; directs the Rush Parkinson's Disease Research Center supported by the Parkinson's Foundation; royalties from Elsevier Publishers, Oxford University Press, Wolters Kluwer.

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Experts Call for Expanded Educational Initiatives on... : Neurology Today - LWW Journals