We are pleased to introduce Dr. Conrad "Chris" Weihl today to answer your questions about Promising Research in IBM. Dr. Weihl, a member of TMA's Medical Advisory Board, is an associate professor of neurology at Washington University in St. Louis, Missouri where his research focuses on myositis and other neuromuscular diseases. In 2013, he was awarded a TMA research grant to study gene sequencing in sIBM. He's the author of many peer-reviewed publications on myositis and is a member of TMA's MAB research committee. He spoke on IBM at TMA's Annual Patient Conference in September in New Orleans. Thank you for joining us today, Dr. Weihl.Ask a Question
I've heard one of the medical advisors is testing a drug called arimoclomol for IBM. What is this and how does it work in IBM? Will I be able to participate in this trial?Dr. Conrad "Chris" Weihl:
Arimoclomol is an oral medication that may increase the ability of muscle to degrade and clear proteins that are toxic and accumulate in IBM muscle. Proof-of-concept studies have been done in mice, but it is still unclear if it will be efficacious in humans.
Is there anything that he or she can do to strengthen the leg and arm muscles?Dr. Conrad "Chris" Weihl:
Exercise is important in IBM. It improves flexibility and improves overall well being. Most importantly, exercise is not detrimental to IBM muscle. However safe exercise is important (no falling).
Genetic Risk FactorParticipant:
I've heard someone has identified the major genetic risk factor for all forms of myositis? Is this true? What is this risk factor and how can I tell if I or my kids have it?Dr. Conrad "Chris" Weihl:
The genetics of sporadic diseases are complicated. There are several studies that have tried to identify a clear genetic risk factor but these effects are very small. This is different from hereditary inclusion body myopathies. In these diseases genetic factors are associated. Anyone with a family history of weakness should consider genetic testing.
I am in my 40s and have just been diagnosed with IBM. I'm still active...don't need assistance yet. But my doctor basically said there's nothing we can do for you. Go home and prepare to be disabled. Isn't there anything out there to offer hope for someone like me?Dr. Conrad "Chris" Weihl:
I think it is an exciting time in myositis research and therapeutics. Even though the BYM388 trial may not have met its endpoint, it illustrated to Pharma that a trial in sIBM is important. It helped establish a rating system for sIBM, and it identified patients and centers to perform the trial. These are huge steps toward clinical trial readiness. This then allows other companies to step in when their products are ready.
Pain When WalkingParticipant:
What I used to walk easily (1 1/2 miles) has very recently been almost impossible to walk without stopping every 25 feet because of pain. Could this be related to my IBM?Dr. Conrad "Chris" Weihl:
IBM itself does not typically cause pain but consequences of weakness can lead to back pain, hip pain, and others. If the pain persists one should check with their doctor and make sure nothing else is causing it.
Does IBM affect the heart muscle?Dr. Conrad "Chris" Weihl:
No IBM does not affect cardiac muscle. It can affect respiratory muscles.
Novartis Trials and New ResearchParticipant:
In light of the disappointing results of the Novartis BYM338 clinical trials for IBM, what new promising research do you foresee in the near future and how will this differ from the Novartis trials? Thank you.Dr. Conrad "Chris" Weihl:
Although the BYM338 trial did not meet its primary endpoint, it did increase muscle volume. Therapies aimed at increasing muscle mass still hold promise and may need to be coupled with exercise or other therapies.
Arimoclomol and Follistatin TrialsParticipant:
What is the latest information on the arimoclomol and follistatin trials? When are they recruiting? How many participants are needed? What sites are involved?Dr. Conrad "Chris" Weihl:
The best place is to look is clinicaltrials.gov.
Editor’s Note: The clinical trial for arimoclomol in IBM patients, led by TMA medical advisor Dr. Mazen Dimachkie, expects to start recruiting 150 patients in January 2017. Study sites are Kansas City and London. The clinical trial involving follistatin and IBM at Nationwide Children’s Hospital in Columbus, Ohio, which was funded in part by TMA, is active but is no longer recruiting patients.
BACE1 Inhibitor VerubecestatParticipant:
Thank you for participating in this discussion. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients. Could this drug help those of us with sIBM? Thanks again.Dr. Conrad "Chris" Weihl:
The data regarding whether beta amyloid in skeletal muscle is causative is still unclear. It seems more likely that it is the accumulation of many proteins. In this case a BACE1 inhibitor would likely be ineffective.
Arimoclomol in Slowing ProgressionParticipant:
Any word on the efficacy of arimoclomol in slowing progression of s-IBM?Dr. Conrad "Chris" Weihl:
A recent manuscript in Science Translational Medicine demonstrates that arimoclomol is safe in IBM patients and improves strength in mouse models.
Arimoclomol Trial CriteriaParticipant:
I was diagnosed with what was termed a classic case of sIBM in 2008. Now, my neurologist says that I have IBM, but he's no longer sure if it is sIBM. Would that disqualify me from the trial for arimoclomol? It just says IBM on the clinical trials site.Dr. Conrad "Chris" Weihl:
I do not know the entry criteria for the arimoclomol trial.
Editor’s Note: You could contact the study recruiter Laura Herbelin (913-588-5095 or LHERBELIN@kumc.edu) for inclusion criteria.
Increased Muscle MassParticipant:
Concerning the Novartis BYM-338 trial for sIBM that was recently discontinued, it's been stated that although the study's primary end point was not reached, it was found that the drug DID produce increased muscle mass. I would think that increased muscle mass would, at the same time, also produce increased muscle strength. Does it? If so, isn't that what we're looking for as a possible IBM treatment?Dr. Conrad "Chris" Weihl:
This is an important question and I think that it will need to be investigated further. I agree intuitively, increased muscle size means stronger muscle. But in a muscle disease, this may not be the case.
Virus Causing IBMParticipant:
Hi Dr. Weihl, what is current thinking on a virus causing IBM? The Epstein-Barr virus that transforms in a small population base like Chicken-pox to shingles, for example.Dr. Conrad "Chris" Weihl:
It is true that rare patients with HIV can develop an sIBM-like illness. In addition, studies have shown that some sIBM patients have, on average, have been exposed to hepatitis C. It is still unclear whether a viral etiology explains the majority of cases of sIBM. However, it is a plausible hypothesis.
Editor’s note: Several researchers, including those funded by TMA, are exploring the question of the role of infection as a cause or trigger of myositis.
HMGCR and NT5C1AParticipant:
Hello Dr. Weihl, I am 47 years old. I was diagnosed with PM last year with subsequent positive HMGCR and just recently diagnosed with IBM with a positive NT5C1A (106units). I am truly blessed that I have such a wonderful doctor that found this early. I work in healthcare and honestly had never heard of IBM until last year.
MY QUESTION: Do you know how many patients you have that have tested positive for both HMGCR and NT5C1A? I was just curious. Sadly, I do not think I will be able to view the live conference because of work, however I did want to ask this question of you.Dr. Conrad "Chris" Weihl:
HMGCR positivity may suggest a treatable form of myositis. I would ask your doctor about this. NT5C1A can be positive in some patients with other autoimmune disorders.
NT5C1A and LGMD Type2JParticipant:
Hello. I am a 61 year old female diagnosed with PM in 2008, then sIBM in 2010. I recently tested positive for the NT5C1A antibody, and I am also genetically positive for LGMD Type2J (TTN defects). Are these things related? What research is being done in these areas and in the area of genetic causes for skeletal muscle disease? Thank you.Dr. Conrad "Chris" Weihl:
NT5C1A antibody status is very helpful in the diagnosis of sIBM. We are actively pursuing studies to explore a genetic contribution to sIBM.
Injecting Adipose-Derived Adult Stem CellsParticipant:
Is there any validity to the growing practice of injecting adipose-derived adult stem cells for the IBM patient? This is being used for many other diseases also to repair and regenerate damaged tissues.Dr. Conrad "Chris" Weihl:
Not at this point. I would be wary of any practice that injects things into sIBM muscle.
Healing Chronic WoundsParticipant:
Is there any research on healing chronic wounds in patients with IBM? My 86-year-old mother has had a wound on her foot for five years, and her wound care doctors have speculated about whether her myositis may be interfering (either directly or indirectly) with healing. Do you know of any resources for chronic wound care in IBM patients?Dr. Conrad "Chris" Weihl:
There is no clear connection between sIBM and wound healing. Patients with decreased muscle mass and immobility can have poor wound healing.
The title of this discussion is "Promising Research in IBM." I'm wondering if you have any new information for us. Thank you.Dr. Conrad "Chris" Weihl:
I would put future research into several buckets:
1) Understanding the natural history of sIBM. It is important that we understand how groups/cohorts of patients progress together. For example how does a person’s weakness change.
2) Biomarkers. It is important that we understand why some patients progress more quickly or more slowly. A biomarker could be a blood test (NTC5IA), a muscle biopsy with or without vacuoles, or findings of a muscle MRI. If we could let a patient know when they were diagnosed what their disease progression would be, that would be very important. Biomarkers may also dictate therapies. One patient may respond if a specific biomarker is present.
3) Genetics. Genetic risk factors may help us understand why some patients have sIBM and others do not. But more importantly, a gene may tell us why one patient with sIBM is different than another patient with sIBM. As we move to an era of personalized medicine, it may be important to tailor therapies to specific people. For example, in a clinical trial some people may have a response but others do not. Overall the trial has “failed,” but what is different about the patients who responded.
4) Therapeutic development. Muscle building agents are currently in clinical trials for other muscle diseases. These treatments increase muscle mass. I believe that it is only a matter of time until one of these therapies will work. However it seems likely that these therapies will work in combination with other treatments. Perhaps immunotherapies in combination. Perhaps drugs that improve muscle regeneration. These types of studies will take time and will feel like they are incremental. We are learning from other degenerative muscle diseases as well.
Hello Dr. Weihl, Is this a true statement that IBM patients can suddenly in the middle of freeway become totally disabled and cause a crash since their muscles becomes useless? Is there a warning sign like more falls before this happens? Thanks.Dr. Conrad "Chris" Weihl:
No there is no risk of sudden paralysis in sIBM.
Cause of sIBMParticipant:
Good afternoon. Information states that sIBM is rare prior to the age of 60. However, the people I have had contact with seem to indicate that almost 70% had onset of the symptoms from age 30 to mid-50's. Is research being done to find a common factor in what may be the cause of sIBM.
Also, should people be given the option of trying medication to see if it can slow the progression of sIBM. I have not been offered any type of medication. I have dysphagia and wonder if research has shown that IVIG can help with swallowing issues.
Will more locations around the USA be part of research and clinical trials for sIBM? Living in rural America does not offer the opportunity to participate in research and trials. It seems that a broader population would be the best for research. Otherwise, it seems to be in Northeast USA and Florida and California where research is done.Dr. Conrad "Chris" Weihl:
sIBM typically affects patients over the age of 45. If someone has symptoms earlier, the diagnosis should be re-evaluated. There is no evidence that IVIG is effect in sIBM.
Editor’s Note: Research and clinical trials take place in locations where the researchers practice. TMA is working to spread the word about this rare disease among physicians and researchers and to attract young physician scientists to take up this cause. We have medical advisors all across the US, including in Minnesota, Kansas, and Missouri (where Dr. Weihl works).
Editor’s Note: IBM diagnosed before the age of 50 is usually hereditary IBM (hIBM) not sporatic IBM. It has a genetic cause rather than an inflammatory cause.
What research has been undertaken regarding the use of medicinal cannabis oil on the symptoms of IBM? Is there any ongoing of planned future research?Dr. Conrad "Chris" Weihl:
I don’t know of any research on cannabis oil.
Alzheimer's Disease ResearchParticipant:
There is said to be a lot of research into Alzheimer's disease, obviously due to its greater prevalence and therefore investment potential from Pharmas. The similarities of the mechanisms in Alzheimer's and IBM are often spoken about. But is there any research into testing new developments and potential new drugs from Alzheimer's drug trials in an IBM cohort? If not can this be an area of review by TMA?Dr. Conrad "Chris" Weihl:
There are similarities between sIBM and Alzheimer’s. In particular both are diseases that affect aged populations. Many therapies aimed at enhancing longevity (resveratrol) may be applicable to many diseases associated with aging. If one could prolong their “healthspan” by ten years this would be a way of avoiding age-associated illness.
Regenerating Muscle StrengthParticipant:
I am 70 years old and was diagnosed with IBM 15 years ago. A little over a year ago I 'graduated' to a wheelchair that is capable of taking me from a sitting to a standing position. For someone who is this far along with IBM what is the likelihood that any substantive future treatment would be productive in regenerating muscle strength or arresting this malady?Dr. Conrad "Chris" Weihl:
This is a difficult question to answer, but muscle regeneration is capable at any age. Understanding how new drugs that treat muscular dystrophies work and if they are effective for wheelchair bound patients may help answer this question.
Pattern of WeaknessParticipant:
Two of the more curious aspects of IBM are the tendencies for (1) muscle weakness to be worse on one side of the body than the other and (2) specific muscle groups being affected more than others (quads, hands muscles, etc). Is there any explanation for this within the new research? Gene proximity on the chromosomes?
Arimoclomol is described as targeting a protein-folding defect in our muscles. How might that relate to my earlier questions? Why would that defect become manifest only after the 5th, 6th, or 7th decades of life?Dr. Conrad "Chris" Weihl:
The pattern of weakness in sIBM is distinctive. However selective vulnerability of specific muscles is not unique to sIBM. In addition, conceptually, many neurodegenerative disorders only affect some neurons but not others. I think we are only beginning to understand the gene environment interactions that occur in diseases such as sIBM.
Encourage IBM ResearchParticipant:
Do you have any suggestions for how we can encourage the NIH to fund more IBM research?Dr. Conrad "Chris" Weihl:
Most research is done at academic institutions and researchers must apply for these as grants. Currently NIH funding is very tight and many good research projects are not funded. The NIH funds good research (funding initiatives are a small portion of this). So the best way to help is to let people know about sIBM, identify good doctors and encourage them to think about studying sIBM. Patient advocacy and awareness is essential.
Editor’s Note: TMA is actively working to encourage physician scientists to study myositis and to fund research devoted to finding answers in the areas Dr. Weihl identifies above. TMA also works to raise awareness of this rare disease among physicians and the general population. Member support and participation in these efforts is essential to this effort.
Thanks to all the members who participated. This concludes today's discussion. Please join TMA in sending a special thank you to Dr. Conrad Weihl for taking the time to answer your questions.Dr. Conrad "Chris" Weihl:
It has been my pleasure. Thank you.