Roche: less frequent dosing for Phase 3 Huntington’s clinical trial, easing burden on patients

With preliminary data in hand, the pharmaceutical firm Roche has announced that it will reduce the frequency of dosing in its historic Phase 3 Huntington’s disease gene-silencing clinical trial, thus easing the burden on the participants, their families, and clinics.

In the recently initiated trial, GENERATION HD1, volunteers will now undergo a bi-monthly instead of a monthly spinal tap (lumbar puncture), Roche announced in a letter to the HD community on March 21, 2019. Lumbar punctures are routine and generally safe procedures, although they can cause side effects such as headaches and bleeding. In GENERATION HD1 it will be a 20-minute outpatient procedure.

Roche based the change on new data taken from 46 volunteers after nine months into the 15-month, so-called open-label extension trial (OLE) that it started for its drug RG6042. Those individuals previously participated in the successful Phase 1/2a clinical trial of RG6042, originally developed by Ionis Pharmaceuticals, Inc. The drug substantially lowered the amount of mutant huntingtin protein, the purported cause of the disease, in the patients’ cerebrospinal fluid. All OLE participants received the drug (as opposed to 25 percent getting the placebo in the 1/2a trial).

“The 15-month open-label extension of the Phase1/2a study is evaluating RG6042 treatment in doses every month (every four weeks) and every two months (every eight weeks),” the Roche announcement stated. “Review of nine-month data showed effects on lowering mutant huntingtin protein levels in the cerebral spinal fluid that support the exploration of less frequent dosing. Based on the totality of the data, including safety and tolerability, there appears to be no overall advantage to treatment monthly versus every two months.”

GENERATION HD1 has three cohorts of clinical trial volunteers, known as “arms.” The planned 660 participants at 80-90 sites around the world are randomly assigned to one of the arms. The study is double-blinded: neither the volunteers nor the trial physicians and their staff know which arm the volunteers are assigned to.

As a result of the update to the trial, all participants will undergo bi-monthly punctures over 25 months. In “arm 1” of the study, the dosing schedule will switch from a monthly puncture and administering the drug bi-monthly (with a placebo in between) to a bi-monthly puncture with no placebo at all. Arm 3 will go from getting a monthly puncture with placebo to a bi-monthly puncture with placebo. 

To test the possibility of reducing potential future drug dosing even further, arm 2 will go from a monthly puncture with the drug to a bi-monthly puncture but with the drug given only every four months (with a placebo in between).

“I am delighted by today’s news that the Generation HD1 protocol will be amended to be less burdensome to trial participants, families and HD clinics around the globe,” George Yohrling, Ph.D., the senior director of mission and scientific affairs for the Huntington’s Disease Society of America, commented in an e-mail. “We are all indebted to the 46 trailblazing research heroes participating in the Phase 1/2a and open-label extension studies that showed us we could not only lower huntingtin in humans, but could do so without monthly infusions of RG6042. Their contributions have forever changed the landscape of HD drug development.”

“The amended trial is good news for the HD community,” LaVonne Goodman, M.D., the founder of Huntington’s Disease Drug Works and a physician to many HD patents, wrote in an e-mail. “For the shorter term, it will make for fewer visits and spinal taps for all involved in the trial. And for the longer term, if the trial at completion is successful by clinical measures, it may further establish whether quarterly dosing is adequate and effective. If so, that would make it easier on the larger number of patients who would need to receive this drug life-long.”

Simplifying the study

Dr. Goodman added: “It was fortunate that the Roche analysis and amendment came at the very beginning of the GENERATION HD1 trial, so that changes could be made without a major time disruption.”

A statement on the Ionis website observed that the new trial design “will greatly simplify the operation of the study.”

Although amending the trial will cause a “slight delay” as Roche seeks regulatory approvals, “we don’t expect this delay will change the timing of study completion, and may even accelerate time to study completion,” the Ionis statement concluded.

“Our team is working to rapidly activate the updated study protocol around the world,” the Roche statement said.

Individuals who had already started GENERATION HD1, which began in January, will be eligible to switch to GEN-EXTEND, an OLE study in which everybody receives RG6042 (no placebo). Participants will receive drug every two or four months.

Great news for the HD community

As the Roche statement noted, the data from the Phase 1/2a OLE do not address the efficacy and long-term safety of the RG6042. That is the purpose of GENERATION HD1.

The update from Roche came in the wake of remarks by GENERATION HD1 scientific coordinator Scott Schobel, M.D., that the company is “actively thinking” about when and how to expand research to target groups beyond the current criterion of early- to mid-stage HD patients aged 25-65. That includes asymptomatic gene carriers like me and sufferers of juvenile HD (click here to read more).

The scientist-written site HDBuzz described the amended trial design as a “surprise” but also a “good thing.”

“Clearly Roche and their partners didn’t predict that we’d be able to deliver [the drug] only every four months when they started the GENERATION HD1 study,” its article on the Roche statement observed. “The fact that they’ve seen data convincing them that we can get away with it is great news for the future of this program, and for future HD community members receiving treatment.”

HDBuzz further noted that other companies using the Ionis-Roche approach (antisense oligonucleotides) can now “consider using longer intervals between treatments.”

As an HD gene carrier and also a sufferer of chronic back pain, I was relieved to learn that the number of lumbar punctures for a potential drug could be as few as three per year.

The Roche announcement coincided with the news that the U.S.-based biotech firm Biogen and its Japanese partner Eisai had announced that they were halting two phase 3 clinical trials for an Alzheimer’s disease drug because an interim analysis concluded that the compound was unlikely to benefit patients. The drug was given through intravenous infusions.

The results of that trial once again underscored the extreme difficulty of treating neurological disorders and the need to the need to have realistic expectations about RG6042 (click here to read more). Not just Alzheimer’s and Huntington’s, but also Parkinson’s, Lou Gehrig’s, and other neurological disorders lack effective treatments.

(Disclosure: I hold a symbolic amount of Ionis shares.)

Roche announces U.S., Canada sites for Phase 3 clinical trial of Huntington’s disease drug

Pharmaceutical firm Roche has announced 26 planned sites in the U.S. and Canada for its historic Phase 3 clinical trial of a gene-silencing drug to slow, halt, or perhaps even reverse the progression of Huntington’s disease.

Called GENERATION HD1, the greatly anticipated trial will test the efficacy of the drug, RG6042. Roche expects to start enrolling volunteers in early 2019.

The announcement comes one year after the successful completion of the Phase 1/2a trial to measure the safety and tolerability of RG6042, developed by Ionis Pharmaceuticals, Inc.

RG6042 dramatically reduced the amount of mutant huntingtin protein in the cerebrospinal fluid (CSF) of trial participants. As a result, Roche took the unusual step of skipping a Phase 2 trial (testing efficacy for the first time) and going directly to a Phase 3 (confirming efficacy in hundreds of participants, or more).

In a statement released December 19 to the Huntington’s Disease Society of America (HDSA) and other patient groups, Roche announced the sites listed below, grouped by province/state.

Canada

Alberta, Edmonton – University of Alberta

British Columbia, Vancouver – University of British Columbia

Ontario, Ottawa – Ottawa Hospital

Ontario, Toronto – Centre for Movement Disorders

Nova Scotia, Halifax – Queen Elizabeth II Health Sciences Centre

Quebec, Montreal – Centre Hospitalier de l’Université de Montréal 

U.S.

Alabama, Birmingham – University of Alabama

Arizona, Phoenix – Barrow Neurological Clinic

California, Davis – University of California, Davis

California, Palo Alto – Stanford University

California, Pasadena – Arcadia Neurology Center

California, San Diego – University of California, San Diego

Colorado, Englewood – Rocky Mountain Movement Disorders Center

District of Columbia, Washington – Georgetown University

Florida, Tampa – University of South Florida

Illinois, Evanston – Northwestern University

Maryland, Baltimore – Johns Hopkins University

Massachusetts, Boston – Beth Israel Deaconess Medical Center

Missouri, St. Louis – Washington University in St. Louis

New York, Amherst – Dent Institute

New York, New York – Columbia University

Pennsylvania, Pittsburgh – University of Pittsburgh Medical Center

Tennessee, Nashville – Vanderbilt University Medical Center

Texas, Houston – University of Texas Health Science Center

Utah, Salt Lake City – University of Utah

Washington, Kirkland – Evergreen Health

Roche plans to announce sites in approximately 13 additional countries in the coming months. It hopes to enroll a global total of 660 volunteers with early HD symptoms at 80 to 90 sites. Each participant will receive the drug or placebo monthly over 25 months through a lumbar puncture (spinal tap), the way into the CSF.

The CSF bathes the brain. Because biopsies of the brain are currently not possible, measuring the effect of the drug in the CSF gives researchers a window onto the effects of the drug.

Moving as ‘quickly as possible’

“It is important to note that these sites are not fully activated nor recruiting yet,” the Roche announcement stated. “We hope to complete the final steps as quickly as possible.”

According to the statement, Roche selected sites based on a variety of factors, including prior experience with HD studies, clinic infrastructure capacity, ability to run the study as quickly and completely as possible, patient population, and geographic location.

The news follows Roche’s announcement last month of 16 sites for the HD Natural History Study, an arm of the RG6042 program to involve 100 observational study volunteers in Canada, Germany, the United Kingdom, and the United States.

The HD Natural History Study will seek to deepen understanding of the natural progression of HD, the role of the mutant huntingtin protein in the disorder, and the assessment of biomarkers (signs of the disease measured in patients) and their efficacy in predicting the effects of the drug. The volunteers will undergo four lumbar punctures to examine their CSF, but receive no drug.

Click here for the full text of Roche’s December 19 statement.

In the U.S. and Canada, HD families can contact Roche/Genentech about the trial at 888-662-6728. Information about the trial is also available at ClinicalTrials.gov.

For additional background on GENERATION HD1, click here.

If effective, RG6042 would be the first treatment to affect the progression of Huntington's.

Stay tuned to this blog for future updates on GENERATION HD1.

Ionis Huntington’s disease drug a step closer to a critical Phase 2 study

Ionis Pharmaceuticals has made two positive announcements about the historic Phase 1 clinical trial of its gene-silencing drug for Huntington’s disease: trial enrollment is complete, and the company will extend the study for all patients who complete Phase 1.

These are key steps on a multi-year path to possible Phase 2 and 3 trials that, if successful, would bring the trial drug, IONIS-HTT_Rx, to market. Typically, all three phases of a clinical trial project take at least five years, although nobody can predict the actual course of a trial.

IONIS-HTT_Rx aims to alleviate HD symptoms by reducing production of the huntingtin protein in brain cells (click here to read more). Ionis launched the Phase 1 trial in September 2015. Three dozen patents are taking part in the trial, expected to be completed by the end of 2017, at sites in Canada, Germany, and England. This first phase aims not to assess success in combating HD but rather simply whether the drug is safe and tolerable.

It marks the first time HD patients are receiving a substance aimed to attack the genetic causes of the disease. It’s also the first time they’re getting a drug via spinal injection.

“The safety and tolerability profile of IONIS-HTT_Rx in the completed cohorts of the Phase 1/2a study supports its continued development,” a June 22 Ionis news release stated. “Patients who complete the Phase 1/2a study will be eligible to participate in an open-label extension (OLE) study that Ionis plans to initiate in the next several months.”

“Open label” means all participants take the drug, in contrast with a “double-blinded” clinical trial like the current Phase 1, where half the patients receive a placebo and neither patients nor doctors know who is receiving the actual drug.

This month’s news provided the strongest indication so far that Ionis and its partner Roche, a much larger multinational pharmaceutical firm with vast clinical trial experience, will take IONIS-HTT_Rx into a larger, critical Phase 2 study, as early as 2018, to measure efficacy.

“Upon completion and full analysis of this study, the next step for this program will be to conduct a study to investigate whether decreasing mutant huntingtin protein with IONIS-HTT_Rx can slow the progression of this terrible disease," Frank Bennett, Ph.D., the Ionis senior vice president of research, said in the release.

Ionis has repeatedly indicated that a Phase 2 study would include U.S. trial sites.

Frank Bennett, Ph.D. (photo by Kristina Bowyer, Ionis)

‘Cautiously optimistic news’

The double-blinded protocol of the Phase 1 HTT_Rx trial insures that bias and other external factors don’t affect the trial results.

As noted, in an OLE each participant receives the actual drug, and usually at the highest dose tried in Phase 1. An OLE allows researchers to gather more data, examine the drug’s effects over a longer period of time, and better prepare for an eventual Phase 2. Patients also potentially benefit by receiving the drug longer.

The HD research website HDBuzz, which is produced by clinicians and scientists, described the Ionis announcements as “cautiously optimistic news.”

“News that the trial is fully recruited and the final patients are going through the procedures is a strong suggestion that even at the highest doses, the drug’s safety looks good,” the HDBuzz report observed. “Despite exhaustive safety testing before going into patients, any drug can produce unwanted effects, so that’s really the best news we could be hoping to hear at this stage.”

Regarding the open-label extension, it added, “We don’t want to read too much into a brief announcement, but running an OLE isn’t cheap for a trial sponsor, so this announcement certainly gives us optimism about the whole HTT_Rx program.”

Signs of HD in the blood

A separate research study, with results published June 7, could help Ionis and Roche researchers evaluate the results of the Phase 1 trial and plan the potential Phase 2 trial.

In what was described as a “major advance in the field of Huntington's disease and neurodegeneration in general,” a team of researchers has identified a potential blood biomarker for HD.

Biomarkers indicate a disease mechanism or drug impact. They are common for many diseases, but the complexity and inaccessibility of the brain have made it extremely difficult for researchers to find them for neurological diseases.

HD scientists have most recently focused on obtaining biomarkers from the cerebral spinal fluid (CSF). However, obtaining CSF, which requires puncturing the spine, is far riskier than drawing blood, the technique used in the new biomarker research.

Led by Ed Wild, M.D., Ph.D., one of the administrators of the IONIS-HTT_Rx trial in England, the new biomarker study demonstrated that a brain protein known as neurofilament light chain (Nfl) appears in the blood of HD patients and presymptomatic gene carriers. (Click here and here to read more.)

Dr. Ed Wild (photo from EdWild.com)

A less invasive measurement

Dr. Bennett of Ionis previously described Nfl as a protein involved in the cytoskeleton, or internal “scaffold,” of neurons. HDBuzz likened it to “the ribs of an umbrella.”

Dr. Wild’s team discovered that, the more advanced the stage of HD, the greater the amount of Nfl in the blood.

“This suggests that a blood test might be able to provide consistent information about the brain, in place of an invasive spinal tap,” HDBuzz commented. “We hope [Nfl] will be added to the arsenal of resources that are helping us to monitor HD and to develop new therapies.”

Indeed, the IONIS-HTT_Rx researchers previously noted that Nfl is one potential biomarker in the Phase 1 trial.

Further research is underway to confirm the Wild team's results and to determine to what extent Nfl can be used as a biomarker.

Pope Francis, Ionis, and the hope for a cure

The Ionis announcements about the clinical trial came as the 32nd annual convention of the Huntington’s Disease Society of America got underway in Schaumberg, IL. In addition to the news release, Ionis issued a letter to the HD community.

“We can assure you our number one goal remains our commitment to advancing IONIS-HTT_Rx development, a drug that has the potential to transform the treatment of HD,” the letter stated.

The positive news also comes in the wake of HDdennomore, the historic audience of the Huntington’s disease community with Pope Francis in Rome on May 18.

Dr. Bennett made a substantial donation to HDdennomore. He and several Ionis officials attended the audience. Dr. Bennett and his wife Paula sat in the front row along with leading HD scientists and dignitaries. They were greeted by Francis.

In his address, the pope recognized the geneticists and scientists “present here, who, for some time, sparing no energy, have dedicated themselves to studying and researching a treatment for Huntington’s disease. Clearly, there is a great deal of expectation surrounding your work: resting on your efforts are the hopes of finding the way to a definitive cure for the disease, but also of improving the living conditions of these brothers and sisters, and of accompaniment, especially in the delicate phases of diagnosis, at the onset of the first symptoms.”

If it succeeds, IONIS-HTT_Rx could fulfill those hopes and show the way to curing other neurological diseases.

Frank Bennett (left), Paula Bennett, and Gene Veritas (aka Kenneth P. Serbin) in St. Peter’s Square just before the audience with Pope Francis, May 18, 2017 (photo by Bianca Serbin)

(Disclosure: I hold a symbolic amount of Ionis shares.)

(Click on the links below for past coverage of the Ionis HD project.)

Ionis Phase I Huntington's disease clinical trial at halfway mark: 'No surprises so far' means good news

Chief Huntington's disease drug hunter: 'every confidence first treatments' in the works

Huntington's disease patients get first dosing in historic Isis Pharmaceuticals' gene-silencing drug trial 

Isis Pharmaceuticals launches historic clinical trial to silence Huntington's disease gene

Moving toward a potential treatment: Isis, CHDI researchers outline upcoming Huntington's disease clinical trial

A key new ally in the search for Huntington's disease treatments

Quickening the pace towards a Huntington's disease gene-silencing clinical trial: pharma giant Roche, Isis enter partnership

Designing the best drug possible to defeat Huntington's disease

Building a 'laser-guided missile' to attack Huntington's disease

Observing the cure in progress

Quickening the pace towards a Huntington’s disease gene-silencing clinical trial: pharma giant Roche, Isis enter partnership

With an infusion of $30 million and access to new technology from the Swiss pharmaceutical giant Roche, Carlsbad, CA-based Isis Pharmaceuticals, Inc., hopes to shorten the timetable for a clinical trial of a potential breakthrough drug for Huntington’s disease. It would attack the disease at its genetic roots and could serve as a preventive medicine.

The partnership, announced April 8, puts Isis in a position “to move very aggressively to getting the drug into clinical trials,” Frank Bennett, Ph.D., the Isis senior vice president for research, said in a phone interview. “It should accelerate the program.”

The deal, which could bring Isis up to $362 million in payments for developing and licensing the drug plus royalties on sales should it prove successful, provides a key piece of the puzzle for the company’s HD program. As a dynamic mid-sized company focused on drug discovery but lacking the capital and infrastructure for large-scale clinical trials and drug commercialization, Isis has finally secured the partner necessary for bringing the potential HD drug to market.

“This is the best news,” said Don Cleveland, Ph.D., an Isis collaborator who helped envision the treatment of HD with the company’s gene-silencing antisense oligonucleotides (ASOs). “Running a clinical trial takes substantial dollars. Isis is a smaller company. Roche is one of the world’s largest and most successful pharmaceutical companies.”

The partnership gives Isis the “confidence” necessary to move from the early to later stages of the clinical trials, Dr. Bennett said. Roche, with its long experience in central nervous system drugs such as Valium, in use since the early 1960s, will not be “dropping the ball as a partner,” he added.

Dr. Frank Bennett (photo by Dr. Ed Wild)

                                                                                                                       

In line with earlier projections, Dr. Bennett stated that Isis still hopes to begin the clinical trial during the first half of 2014.

Shuttling drugs into the brain

The ASOs diminish the production of the huntingtin protein by eliminating huntingtin RNA in brain cells, which are destroyed in HD, producing motor, cognitive, and psychiatric difficulties in affected individuals. (Click here to read more about the efforts to design the drug and bring it to trial.)

Isis and Roche will experiment with the latter’s “brain shuttle” technology, which, if successful, would allow greater penetration of the drug into the brain and make it far easier for patients to take.

Isis first aimed to implant a pump in a patient’s abdomen and inject the drug directly into the brain. Then it moved to an injection into the cerebral spinal fluid (CSF) through a quarter-sized port implanted near the rib cage, with a catheter running to the area of the spinal cord.

However, as Dr. Bennett explained, with the brain shuttle technique, patients would simply need a subcutaneous injection (under the skin) similar to the kind taken by diabetes patients.

The brain shuttle would “allow us to use systemic dosing,” Dr. Bennett explained. (Systemic dosing means the drug enters the bloodstream and is thus more available in the body in comparison with an injection into the CSF.)

“It’s much more convenient,” he added. “It’s a better tolerated therapy. It could capture the symptoms earlier, maybe even prevent the development of the disease.”

Glimpsing the Holy Grail?

That convenience also makes it easier to administer the drug to gene-positive asymptomatic individuals, Dr. Bennett noted.

For ethical and scientific reasons, people in this group (including me) have rarely, if ever, participated in HD clinical trials. Basically, scientists haven’t yet figured out how to measure how a drug could benefit this group. In addition, its risk-benefit ratio is higher than it is for people with symptoms. Solving these problems, and thus completely preventing HD (as well as other neurological diseases such as Alzheimer’s), is what I have called the Holy Grail of the research community.

For the first time, the Isis-Roche partnership suggests how the grail might be found. With reduced risks, participation in trials becomes more attractive, and ethical barriers diminish. In addition, the very entry of asymptomatic people into a trial permits the collection of data about efficacy specific to that group.

However, Dr. Bennett cautioned that this approach would most likely be reserved for second-generation clinical trials. Until the initial trials are completed, it’s impossible to venture a guess about the timetable for a second generation.

“As a scientist, you can always make something better, but you have to be careful,” he said of the time needed to develop the brain shuttle for ASOs. “For a patient that’s suffering from the disease, you don’t want to over-engineer and delay getting it to the patient.”

Dr. Cleveland pointed out that the brain shuttle approach is new and has yet to be proven as a way to transport drugs into the brain.

“That’s precisely why you want to have partners like Roche,” he said. “They’ve been delivering things to the central nervous system for a long time. There’s tremendous promise. The challenge will be to bring that promise into real fruition.”

Isis and Roche will conduct joint research to discover whether they can attach the ASO to molecules that naturally shuttle other, necessary molecules into the brain across the blood brain barrier, which shields the brain from foreign substances that might cause harm and prevents the ASOs on their own from entering.

Key details and collaborators

“Huntington’s is a severely debilitating neurodegenerative disease and a large unmet medical need,” Luca Santarelli, Head of Neuroscience and Small Molecules Research at Roche, stated in the press release announcing the partnership. “Treatments are urgently needed, and we believe that the Isis approach in combination with Roche’s brain shuttle represents one of the most advanced programs targeting the cause of HD with the aim of slowing down or halting the progression of this disease.”

Under the deal, the $30 million investment from Roche will underwrite the project through Phase IIA of the three phases of the first-round clinical trial, with Isis retaining control of the project, Dr. Bennett said. If Phase IIA proves successful, Roche would conduct the more extensive Phase III trial, seek regulatory approval for the drug, and market it.

The agreement also stipulates that over time Isis will reimburse the CHDI Foundation, Inc., the multi-million-dollar non-profit virtual biotech firm that funded and advised the HD research at both Isis and Dr. Cleveland’s lab at the Ludwig Institute for Cancer Research at the University of California, San Diego. CHDI will initially receive $1.5 million, with additional reimbursements occurring as Isis receives project milestone payments from Roche. CHDI will continue to advise Isis and Roche on HD research.

“This is an exciting development for the HD community, and a testament to the excellent work that Isis has done to develop their oligonucleotide therapeutic for HD,” said Robi Blumenstein, the president of CHDI Management, Inc., the firm that carries out the goals of the CHDI Foundation. “It's very encouraging that Roche, a pharmaceutical company with a great track record in central nervous system disorders, has now entered into developing treatments for HD. CHDI looks forward to working with both companies to steer this novel approach to the clinic as soon as possible."

Isis, Dr. Cleveland, and CHDI are currently conducting a large experiment to find HD biomarkers (signs of disease) that will enable them to determine the proper dose of the ASO drug and to measure its impact during the clinical trial.

David Corey, Ph.D., of the University of Texas Southwestern also collaborated with Isis on the gene-silencing project.

(Next time: my personal thoughts on the Isis-Roche project as a powerful new sign of hope for the HD community.)

Big decisions while facing the threat of Huntington’s disease

At every turn of life, we all make big decisions such as choosing a career, a mate, a home, and the number of children to conceive.

Living with the knowledge of a positive test for a devastating condition such as Huntington’s disease radically complicates such decisions. Coupled with the deep stigma associated with HD, the fear of the onset of symptoms magnifies the stress and doubt that come with such turning points.

As I have frequently revealed in my writings and in speeches about HD, I have faced life-changing decisions about a feeding tube for my HD-stricken mother, my genetic test, and the test of our daughter while still in the womb. (Thankfully, she tested negative!)

Planning for the inevitable symptoms of this currently untreatable disease has also profoundly altered my career, leading me into a new field far different from my original focus on Brazilian history: the history of science, technology, and medicine.

With my definitive exit from the “HD closet” last fall, I have begun to integrate this new intellectual passion into my professional life.

Professional excitement

Lately, however, I’ve relived the intensity of how the threat of HD affected my professional decisions.

With the surprise resignation of Pope Benedict XVI on February 11 and the emergence of several potential successors from among Latin America’s cardinals, my expertise on the Roman Catholic Church’s actions in the region and its relations with the region’s dictatorships – topics usually of no interest to the media and the general public – suddenly were in demand.

The election of Pope Francis I created great excitement: his initial attitudes and actions indicated that he might very well attempt to clean up the corruption and abuses that have plagued the institution.

At the same time, it rapidly became apparent that the new pope had had his own complex and (to some) controversial relationship with the Argentine dictatorship, which carried out a “dirty war” against Argentines from 1976-1983.

In the period before and after the election of Pope Francis I, I gave eleven interviews and answered a number of other queries from newsmagazines and radio and TV outlets.

My personal excitement culminated with the publication on March 17 of an op-ed article, outlining the potential paths of the Church under Francis I, in one of Brazil’s most prestigious newspapers, the Folha de S. Paulo, followed  by a quotation from me about the Argentine branch of the Church in a front-page story in The New York Times.

As I told a number of friends, never before and probably never again will my scholarly work on the Catholic Church command so much attention in the United States.

Throughout all this, I began to relive the past thrills and satisfaction of researching the Church, publishing books on the topic, and discussing my work in the Brazilian media.

My wife seemed especially happy to see me enjoying, for the first time in a very long while, recognition for my original career path. For her, it was a relief from that dogged, sometimes seemingly one-dimensional aspect of my life involving the fight against HD.

Second-guessing the past, but welcoming the future

As a result, I began second-guessing my decision in 2007 to turn down a job to help run a prestigious Latin American studies center in Florida in order to remain in biotech-rich San Diego to focus on the fight against HD. Staying put also helped safeguard my family’s financial future by allowing my wife to keep her good job and better-than-average retirement plan – absolutely essential if HD were to leave me disabled.

I thought of the HD people I had recently read about who had roughly the same degree of genetic mutation as I did and managed to avoid symptoms until their sixties and even continued to work after onset.

However, in the process of second-guessing, I recalled how I made that decision when the memories of my mother’s demise just a year and a half before still haunted me.

In hindsight, it’s easy to argue that I should have taken the other job and not worried so much about HD.

However, hindsight also reminds me of how HD completely destroyed my mother’s ability to work, to communicate, and to care for herself.

My wife and I made our big decision with the best information available to us at that moment.

I quickly reminded myself that rather than reliving the past, I must look to the future, value the intellectual flexibility of my university, and fulfill the plans I have mapped out for myself. I will be seeking connections with my university’s neuroscience program and social outreach project in order to promote brain health as a national priority.

Indeed, my dean has fully supported me after my exit from the HD closet. I felt especially reaffirmed with the publication of a feature article about my journey with HD on the university’s website.

The decision to pursue the history of science, technology, and medicine has exposed me to new vistas of the human story. HD is a challenge – but also a gift that has led to profound intellectual and personal growth.

The real successes and challenges

I savored my public moment as a Latin America scholar.

However, it stood in sharp contrast to the intensity and immensity of the challenge to avoid HD symptoms and contribute to the defeat of the disease.

While friends and colleagues were impressed with the recognition of my expertise, I quietly pondered the truly significant accomplishment for me during the week of Francis I’s election: the successful arrangement of a meeting between Paulo Vannuchi, Brazil’s former Minister of Human Rights, and Taíse Cadore, the president of the Associação Brasil Huntington. They discussed the crucial need to involve Brazil’s Ministry of Health in the fight against HD in Brazil, which will host the 2013 World Congress on Huntington’s Disease from September 15-18.

Ultimately, scientists’ work will go for naught unless events such as the World Congress can draw more people into the HD cause and involve them in the all-crucial research studies and clinical trials.

Participating in a study

On March 13, as I monitored the Internet for news of the papal conclave, I spoke to a researcher at the Huntington’s Disease Society of America Center for Excellence at Iowa Hospitals and Clinics, one of the sites for a key study known as PREDICT-HD, an observational study of the earliest signs of HD that needs asymptomatic, gene-positive volunteers.

PREDICT-HD will help establish ways to measure the efficacy of potential treatments.

Participating in PREDICT-HD represents another big decision for my family and me. The study requires the presence of a spouse or partner, who must answer a questionnaire about the gene-positive individual. All three of us must spend two days traveling and at least two days in Iowa.

The PREDICT-HD also involves a voluntary spinal tap so that cerebral spinal fluid from gene-positive people can be studied for the effects of HD and ways to measure the efficacy of potential treatments.

Spinal taps are routine but, like any procedure, involve risks such as a debilitating headache that could require emergency room treatment. In my case, it means that I will probably notify my health insurance plan for the very first time of my gene-positive status. I want to make sure I can safely undergo the tap, and I want to have my plan doctors on standby in the event of complications.

In and of itself, informing my health plan about HD represents yet another significant shift in my medical, psychological, and emotional approach to the disease.

Channeling the positive energy

As the HD researcher and I finished our discussion about PREDICT-HD, I saw the announcement of breaking news about white smoke from the Sistine Chapel: a new pope had been chosen.

Minutes later, my daughter and I watched as Francis I appeared on the balcony of St. Peter’s Basilica in Rome and humbly prayed the Our Father and Hail Mary with the crowd gathered below – the same prayers she and I say together each night, alternating in English and Portuguese, before she goes to sleep.

I felt a new beginning for the Church.

In the days since then, I have frequently asked myself how I can channel the deep fulfillment and positive energy from my study of this troubled but nevertheless key institution into the effort to relieve the suffering caused by Huntington’s and so many other devastating diseases.

As I wrote in my op-ed piece on the pope, Francis I “seems to be saying that believers, and the rest of the world, must rediscover the fundamentals of human existence.”

In his inauguration homily on March 19, Francis I stated that “authentic power is service.” As pope he must protect “the hungry, the thirsty, the stranger, the naked, the sick and those in prison.”

For me, this means protecting my family from the consequences of HD and striving to do my small part to help others.