Promising Research in IBM

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.

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.

There is no clear connection between sIBM and wound healing. Patients with decreased muscle mass and immobility can have poor wound healing.

Not at this point. I would be wary of any practice that injects things into sIBM muscle.

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 antibody status is very helpful in the diagnosis of sIBM. We are actively pursuing studies to explore a genetic contribution to sIBM.

No there is no risk of sudden paralysis in sIBM.

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.

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.

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.

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.

I don’t know of any research on cannabis oil.

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.

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.

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.

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.

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.

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.

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).

No IBM does not affect cardiac muscle. It can affect respiratory muscles.

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.

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.

A recent manuscript in Science Translational Medicine demonstrates that arimoclomol is safe in IBM patients and improves strength in mouse models.

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.

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.